2011 ASCO Annual Meeting

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – The combination of two oral drugs that target selected molecules in the mitogen-activated protein kinase signaling pathway appears to be safe and active in patients with melanoma, a phase I trial found. The finding was reported at the annual meeting of the American Society of Clinical Oncology.

Among patients with BRAF-mutated melanoma who had not previously received an agent targeting that molecule, the combination of an investigational BRAF inhibitor (GSK436) and an investigational MEK inhibitor (GSK212) achieved a response rate of 50%-77%.

Both drugs could be used in their full monotherapy doses when combined. And the combination was well tolerated; indeed, certain adverse effects that were seen with each drug when used alone (such as a rash with MEK inhibitor monotherapy) were less common when they were used together.

"The clinical activity in BRAF V600–mutant melanoma is definitely compelling," commented lead investigator Dr. Jeffrey R. Infante, a medical oncologist and director of drug development at the Sarah Cannon Research Institute in Nashville, Tenn. "But like everyone in the audience, I think, we are anxiously awaiting the long-term durability" data. "This combination could have potential implications in multiple tumor types outside of melanoma and have broader impacts in oncology," he added.

"I am really impressed by these data," said discussant Dr. Reinhard Dummer of the University Hospital Zurich. In particular, although the trial was not designed to assess responses and the follow-up is still short, some of the patients had complete remissions, he noted.

"I have to admit, I never thought that we could have complete remissions with kinase inhibitors, so I hope that they will continue," he said. "With this in mind, I think we can reset our goals for melanoma research: We don’t want to go for progression-free survival in the future, but we should go for cure."

The reduced rate of the inflammatory rash with the combination was "very surprising," given that the rash is likely a stress response resulting from the MEK inhibitor’s effect on the MAP [mitogen-activated protein] kinase pathway in the skin, Dr. Dummer said. "How can it happen that this rash is reduced in the combination with the BRAF inhibitor? This is completely not understandable for me. Cutaneous biologists will have a lot of fun to study this model."

Both drugs, which are manufactured by GlaxoSmithKline, have previously shown activity as single agents in patients who have melanoma with BRAF V600 gene mutations, which are found in about half of cases. "The goal was to ... give [the drugs] together and really hope to get a profound synergy in combination in pathway inhibition," explained Dr. Infante.

Patients were eligible for the trial if they had melanoma or another cancer with a V600 mutation in the BRAF gene. Those who had stable brain metastases after surgery or radiosurgery could enroll.

Patients having certain eye conditions were excluded because of previously identified, related issues associated with MEK inhibitor therapy. But there was no limit on the number of prior therapies.

In part A of the study, the investigators tested for drug-drug interactions. In part B, they performed dose escalation, assessed safety and activity, and enrolled expansion cohorts of patients, such as those who had previously received a BRAF inhibitor.

Among the eight patients in part A, there was no effect of the MEK inhibitor when given daily on the pharmacokinetics of single doses of the BRAF inhibitor, Dr. Infante reported.

Of the 109 patients in part B, fully 93% had melanoma and 91% specifically had the V600E BRAF mutation. The majority (54%) had received at least two prior lines of systemic anticancer therapy.

Dose-escalation results showed that both drugs could be given in combination at their full monotherapy doses (150 mg twice daily of the BRAF inhibitor and 2 mg once daily of the MEK inhibitor), largely without dose-limiting toxicities.

Only one dose-limiting toxicity was seen with the full dose of each drug. The patient developed a neutrophilic panniculitis, manifesting as painful red nodules on the thorax and extremities, in association with fever and chills. It resolved with discontinuation of the drugs and steroid therapy.

Across the dose combinations, 79% of patients experienced an adverse event and 19% experienced a grade 3 or higher adverse event, most often neutropenia, leukopenia, diarrhea, and fever. There was no clear association with doses, according to Dr. Infante.

In a finding as yet without explanation, certain adverse events that had been seen previously with each drug when they were given alone were actually less common when they were combined. Specifically, rash occurred in 25% of patients, whereas historically it has been seen in 75%-80% of those given the MEK inhibitor alone. And squamous cell carcinoma and other hyperproliferative skin lesions were seen in roughly 1%, whereas they have been seen in 7%-15% of those given the BRAF inhibitor alone.

Among the 71 patients with melanoma who had not previously received a BRAF inhibitor, the rate of unconfirmed objective response (complete or partial response) ranged from 50% to 77%, depending on the dose combination. Five patients had complete responses. For comparison, the response rate in BRAF-mutated melanoma has been 63% with the BRAF inhibitor alone and 40% with the MEK inhibitor alone.

Additionally, the rate of disease control (complete response, partial response, or stable disease) ranged from 95% to 100%, Dr. Infante reported. And the large majority of patients (83%) are still receiving combination therapy.

Analyses among the 24 patients with melanoma who had previously received a BRAF inhibitor showed that about half had a reduction in tumor size. There was no clear difference according to the duration of the earlier BRAF inhibitor therapy.

The investigators are now conducting a phase II trial in which 150 patients with V600E- or V600K-mutant melanoma are being randomly assigned to therapy with the BRAF inhibitor alone or in combination with the MEK inhibitor at two dose levels.

Dr. Dummer, the discussant, noted that obtaining biopsies is "very crucial" to understanding how such novel antimelanoma therapies are working. "Our patients, when you explain this to them, they will agree to sequential biopsies," he commented. "And I encourage all of you to participate in trials with a very strong translational research" component.

Dr. Infante reported that he is an unpaid consultant to GlaxoSmithKline, and that several coauthors are GSK employees. Dr. Dummer reported that he is a consultant to Bristol-Myers Squibb, Merck, Novartis, and Roche, and receives honoraria from Bristol-Myers Squibb.

CHICAGO – The combination of two oral drugs that target selected molecules in the mitogen-activated protein kinase signaling pathway appears to be safe and active in patients with melanoma, a phase I trial found. The finding was reported at the annual meeting of the American Society of Clinical Oncology.

Among patients with BRAF-mutated melanoma who had not previously received an agent targeting that molecule, the combination of an investigational BRAF inhibitor (GSK436) and an investigational MEK inhibitor (GSK212) achieved a response rate of 50%-77%.

Both drugs could be used in their full monotherapy doses when combined. And the combination was well tolerated; indeed, certain adverse effects that were seen with each drug when used alone (such as a rash with MEK inhibitor monotherapy) were less common when they were used together.

"The clinical activity in BRAF V600–mutant melanoma is definitely compelling," commented lead investigator Dr. Jeffrey R. Infante, a medical oncologist and director of drug development at the Sarah Cannon Research Institute in Nashville, Tenn. "But like everyone in the audience, I think, we are anxiously awaiting the long-term durability" data. "This combination could have potential implications in multiple tumor types outside of melanoma and have broader impacts in oncology," he added.

"I am really impressed by these data," said discussant Dr. Reinhard Dummer of the University Hospital Zurich. In particular, although the trial was not designed to assess responses and the follow-up is still short, some of the patients had complete remissions, he noted.

"I have to admit, I never thought that we could have complete remissions with kinase inhibitors, so I hope that they will continue," he said. "With this in mind, I think we can reset our goals for melanoma research: We don’t want to go for progression-free survival in the future, but we should go for cure."

The reduced rate of the inflammatory rash with the combination was "very surprising," given that the rash is likely a stress response resulting from the MEK inhibitor’s effect on the MAP [mitogen-activated protein] kinase pathway in the skin, Dr. Dummer said. "How can it happen that this rash is reduced in the combination with the BRAF inhibitor? This is completely not understandable for me. Cutaneous biologists will have a lot of fun to study this model."

Both drugs, which are manufactured by GlaxoSmithKline, have previously shown activity as single agents in patients who have melanoma with BRAF V600 gene mutations, which are found in about half of cases. "The goal was to ... give [the drugs] together and really hope to get a profound synergy in combination in pathway inhibition," explained Dr. Infante.

Patients were eligible for the trial if they had melanoma or another cancer with a V600 mutation in the BRAF gene. Those who had stable brain metastases after surgery or radiosurgery could enroll.

Patients having certain eye conditions were excluded because of previously identified, related issues associated with MEK inhibitor therapy. But there was no limit on the number of prior therapies.

In part A of the study, the investigators tested for drug-drug interactions. In part B, they performed dose escalation, assessed safety and activity, and enrolled expansion cohorts of patients, such as those who had previously received a BRAF inhibitor.

Among the eight patients in part A, there was no effect of the MEK inhibitor when given daily on the pharmacokinetics of single doses of the BRAF inhibitor, Dr. Infante reported.

Of the 109 patients in part B, fully 93% had melanoma and 91% specifically had the V600E BRAF mutation. The majority (54%) had received at least two prior lines of systemic anticancer therapy.

Dose-escalation results showed that both drugs could be given in combination at their full monotherapy doses (150 mg twice daily of the BRAF inhibitor and 2 mg once daily of the MEK inhibitor), largely without dose-limiting toxicities.

Only one dose-limiting toxicity was seen with the full dose of each drug. The patient developed a neutrophilic panniculitis, manifesting as painful red nodules on the thorax and extremities, in association with fever and chills. It resolved with discontinuation of the drugs and steroid therapy.

Across the dose combinations, 79% of patients experienced an adverse event and 19% experienced a grade 3 or higher adverse event, most often neutropenia, leukopenia, diarrhea, and fever. There was no clear association with doses, according to Dr. Infante.

In a finding as yet without explanation, certain adverse events that had been seen previously with each drug when they were given alone were actually less common when they were combined. Specifically, rash occurred in 25% of patients, whereas historically it has been seen in 75%-80% of those given the MEK inhibitor alone. And squamous cell carcinoma and other hyperproliferative skin lesions were seen in roughly 1%, whereas they have been seen in 7%-15% of those given the BRAF inhibitor alone.

Among the 71 patients with melanoma who had not previously received a BRAF inhibitor, the rate of unconfirmed objective response (complete or partial response) ranged from 50% to 77%, depending on the dose combination. Five patients had complete responses. For comparison, the response rate in BRAF-mutated melanoma has been 63% with the BRAF inhibitor alone and 40% with the MEK inhibitor alone.

Additionally, the rate of disease control (complete response, partial response, or stable disease) ranged from 95% to 100%, Dr. Infante reported. And the large majority of patients (83%) are still receiving combination therapy.

Analyses among the 24 patients with melanoma who had previously received a BRAF inhibitor showed that about half had a reduction in tumor size. There was no clear difference according to the duration of the earlier BRAF inhibitor therapy.

The investigators are now conducting a phase II trial in which 150 patients with V600E- or V600K-mutant melanoma are being randomly assigned to therapy with the BRAF inhibitor alone or in combination with the MEK inhibitor at two dose levels.

Dr. Dummer, the discussant, noted that obtaining biopsies is "very crucial" to understanding how such novel antimelanoma therapies are working. "Our patients, when you explain this to them, they will agree to sequential biopsies," he commented. "And I encourage all of you to participate in trials with a very strong translational research" component.

Dr. Infante reported that he is an unpaid consultant to GlaxoSmithKline, and that several coauthors are GSK employees. Dr. Dummer reported that he is a consultant to Bristol-Myers Squibb, Merck, Novartis, and Roche, and receives honoraria from Bristol-Myers Squibb.

CHICAGO – The combination of two oral drugs that target selected molecules in the mitogen-activated protein kinase signaling pathway appears to be safe and active in patients with melanoma, a phase I trial found. The finding was reported at the annual meeting of the American Society of Clinical Oncology.

Among patients with BRAF-mutated melanoma who had not previously received an agent targeting that molecule, the combination of an investigational BRAF inhibitor (GSK436) and an investigational MEK inhibitor (GSK212) achieved a response rate of 50%-77%.

Both drugs could be used in their full monotherapy doses when combined. And the combination was well tolerated; indeed, certain adverse effects that were seen with each drug when used alone (such as a rash with MEK inhibitor monotherapy) were less common when they were used together.

"The clinical activity in BRAF V600–mutant melanoma is definitely compelling," commented lead investigator Dr. Jeffrey R. Infante, a medical oncologist and director of drug development at the Sarah Cannon Research Institute in Nashville, Tenn. "But like everyone in the audience, I think, we are anxiously awaiting the long-term durability" data. "This combination could have potential implications in multiple tumor types outside of melanoma and have broader impacts in oncology," he added.

"I am really impressed by these data," said discussant Dr. Reinhard Dummer of the University Hospital Zurich. In particular, although the trial was not designed to assess responses and the follow-up is still short, some of the patients had complete remissions, he noted.

"I have to admit, I never thought that we could have complete remissions with kinase inhibitors, so I hope that they will continue," he said. "With this in mind, I think we can reset our goals for melanoma research: We don’t want to go for progression-free survival in the future, but we should go for cure."

The reduced rate of the inflammatory rash with the combination was "very surprising," given that the rash is likely a stress response resulting from the MEK inhibitor’s effect on the MAP [mitogen-activated protein] kinase pathway in the skin, Dr. Dummer said. "How can it happen that this rash is reduced in the combination with the BRAF inhibitor? This is completely not understandable for me. Cutaneous biologists will have a lot of fun to study this model."

Both drugs, which are manufactured by GlaxoSmithKline, have previously shown activity as single agents in patients who have melanoma with BRAF V600 gene mutations, which are found in about half of cases. "The goal was to ... give [the drugs] together and really hope to get a profound synergy in combination in pathway inhibition," explained Dr. Infante.

Patients were eligible for the trial if they had melanoma or another cancer with a V600 mutation in the BRAF gene. Those who had stable brain metastases after surgery or radiosurgery could enroll.

Patients having certain eye conditions were excluded because of previously identified, related issues associated with MEK inhibitor therapy. But there was no limit on the number of prior therapies.

In part A of the study, the investigators tested for drug-drug interactions. In part B, they performed dose escalation, assessed safety and activity, and enrolled expansion cohorts of patients, such as those who had previously received a BRAF inhibitor.

Among the eight patients in part A, there was no effect of the MEK inhibitor when given daily on the pharmacokinetics of single doses of the BRAF inhibitor, Dr. Infante reported.

Of the 109 patients in part B, fully 93% had melanoma and 91% specifically had the V600E BRAF mutation. The majority (54%) had received at least two prior lines of systemic anticancer therapy.

Dose-escalation results showed that both drugs could be given in combination at their full monotherapy doses (150 mg twice daily of the BRAF inhibitor and 2 mg once daily of the MEK inhibitor), largely without dose-limiting toxicities.

Only one dose-limiting toxicity was seen with the full dose of each drug. The patient developed a neutrophilic panniculitis, manifesting as painful red nodules on the thorax and extremities, in association with fever and chills. It resolved with discontinuation of the drugs and steroid therapy.

Across the dose combinations, 79% of patients experienced an adverse event and 19% experienced a grade 3 or higher adverse event, most often neutropenia, leukopenia, diarrhea, and fever. There was no clear association with doses, according to Dr. Infante.

In a finding as yet without explanation, certain adverse events that had been seen previously with each drug when they were given alone were actually less common when they were combined. Specifically, rash occurred in 25% of patients, whereas historically it has been seen in 75%-80% of those given the MEK inhibitor alone. And squamous cell carcinoma and other hyperproliferative skin lesions were seen in roughly 1%, whereas they have been seen in 7%-15% of those given the BRAF inhibitor alone.

Among the 71 patients with melanoma who had not previously received a BRAF inhibitor, the rate of unconfirmed objective response (complete or partial response) ranged from 50% to 77%, depending on the dose combination. Five patients had complete responses. For comparison, the response rate in BRAF-mutated melanoma has been 63% with the BRAF inhibitor alone and 40% with the MEK inhibitor alone.

Additionally, the rate of disease control (complete response, partial response, or stable disease) ranged from 95% to 100%, Dr. Infante reported. And the large majority of patients (83%) are still receiving combination therapy.

Analyses among the 24 patients with melanoma who had previously received a BRAF inhibitor showed that about half had a reduction in tumor size. There was no clear difference according to the duration of the earlier BRAF inhibitor therapy.

The investigators are now conducting a phase II trial in which 150 patients with V600E- or V600K-mutant melanoma are being randomly assigned to therapy with the BRAF inhibitor alone or in combination with the MEK inhibitor at two dose levels.

Dr. Dummer, the discussant, noted that obtaining biopsies is "very crucial" to understanding how such novel antimelanoma therapies are working. "Our patients, when you explain this to them, they will agree to sequential biopsies," he commented. "And I encourage all of you to participate in trials with a very strong translational research" component.

Dr. Infante reported that he is an unpaid consultant to GlaxoSmithKline, and that several coauthors are GSK employees. Dr. Dummer reported that he is a consultant to Bristol-Myers Squibb, Merck, Novartis, and Roche, and receives honoraria from Bristol-Myers Squibb.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.