TBD Meeting (3035-19)

CHICAGO – Olanzapine plus aprepitant, palonosetron, and dexamethasone (APD) can be considered a new standard antiemetic therapy for patients receiving cisplatin-based chemotherapy, according to a speaker at the annual meeting of the American Society for Clinical Oncology.

A 5 mg dose of olanzapine plus APD produced significantly higher complete response (CR) rates than APD plus placebo in a phase 3 trial, said Hironobu Hashimoto, BPharm, of the National Cancer Center Hospital in Tokyo.

In addition, olanzapine plus APD had a significantly longer time to treatment failure and produced higher rates of complete control and total control. However, rates of somnolence, dizziness, and dry mouth were significantly higher with olanzapine plus APD.

In the phase 3 J-FORCE study, Mr. Hashimoto and his colleagues evaluated olanzapine at 5 mg plus standard antiemetic therapy (APD) for the prevention of chemotherapy-induced nausea and vomiting.

The trial enrolled 710 patients, ages 22-75 years, who had malignant solid tumors and were receiving cisplatin-based chemotherapy for the first time. The patients were randomized to olanzapine plus APD or APD plus placebo.

There were 354 patients evaluable for efficacy in the olanzapine arm and 351 in the placebo arm. The primary endpoint was CR, which was defined as no vomiting and no rescue medications, in the delayed phase (24 hours to 120 hours).

The CR rate in the delayed phase was 79% in the olanzapine arm and 66% in the placebo arm (P less than .001). The CR rate in the acute phase (0 to 24 hours) was 95% and 89%, respectively (P equal to .002), and the overall CR rate was 78% and 64%, respectively (P less than .001).

The time to treatment failure was significantly longer in the olanzapine arm (P less than .001).

The rate of complete control in the overall period (0 to 120 hours) was 76% in the olanzapine arm and 61% in the placebo arm (P less than .001). Complete control was defined as no emesis, no rescue medication, and no nausea or low-grade nausea.

The rate of total control in the overall period was 59% in the olanzapine arm and 48% in the placebo arm (P = .005). Total control was defined as no emesis, no rescue medication, and no nausea.

Treatment-related adverse events (in the olanzapine and placebo arms, respectively) included constipation (15% and 11%), hiccups (10% and 6%), somnolence (43% and 33%), insomnia (5% and 7%), dizziness (8% and 3%), and dry mouth (21% and 9%).

Adverse events that occurred significantly more often with olanzapine were somnolence (P = .011), dizziness (P = .004), and dry mouth (P  less than .001).

This study was sponsored by the Japan Agency for Medical Research and Development (AMED). Mr. Hashimoto said he had nothing to disclose. Other investigators involved in this study disclosed relationships with numerous pharmaceutical companies.

jensmith@mdedge.com

SOURCE: Hashimoto H et al. ASCO 2019. Abstract 11503.

CHICAGO – Olanzapine plus aprepitant, palonosetron, and dexamethasone (APD) can be considered a new standard antiemetic therapy for patients receiving cisplatin-based chemotherapy, according to a speaker at the annual meeting of the American Society for Clinical Oncology.

A 5 mg dose of olanzapine plus APD produced significantly higher complete response (CR) rates than APD plus placebo in a phase 3 trial, said Hironobu Hashimoto, BPharm, of the National Cancer Center Hospital in Tokyo.

In addition, olanzapine plus APD had a significantly longer time to treatment failure and produced higher rates of complete control and total control. However, rates of somnolence, dizziness, and dry mouth were significantly higher with olanzapine plus APD.

In the phase 3 J-FORCE study, Mr. Hashimoto and his colleagues evaluated olanzapine at 5 mg plus standard antiemetic therapy (APD) for the prevention of chemotherapy-induced nausea and vomiting.

The trial enrolled 710 patients, ages 22-75 years, who had malignant solid tumors and were receiving cisplatin-based chemotherapy for the first time. The patients were randomized to olanzapine plus APD or APD plus placebo.

There were 354 patients evaluable for efficacy in the olanzapine arm and 351 in the placebo arm. The primary endpoint was CR, which was defined as no vomiting and no rescue medications, in the delayed phase (24 hours to 120 hours).

The CR rate in the delayed phase was 79% in the olanzapine arm and 66% in the placebo arm (P less than .001). The CR rate in the acute phase (0 to 24 hours) was 95% and 89%, respectively (P equal to .002), and the overall CR rate was 78% and 64%, respectively (P less than .001).

The time to treatment failure was significantly longer in the olanzapine arm (P less than .001).

The rate of complete control in the overall period (0 to 120 hours) was 76% in the olanzapine arm and 61% in the placebo arm (P less than .001). Complete control was defined as no emesis, no rescue medication, and no nausea or low-grade nausea.

The rate of total control in the overall period was 59% in the olanzapine arm and 48% in the placebo arm (P = .005). Total control was defined as no emesis, no rescue medication, and no nausea.

Treatment-related adverse events (in the olanzapine and placebo arms, respectively) included constipation (15% and 11%), hiccups (10% and 6%), somnolence (43% and 33%), insomnia (5% and 7%), dizziness (8% and 3%), and dry mouth (21% and 9%).

Adverse events that occurred significantly more often with olanzapine were somnolence (P = .011), dizziness (P = .004), and dry mouth (P  less than .001).

This study was sponsored by the Japan Agency for Medical Research and Development (AMED). Mr. Hashimoto said he had nothing to disclose. Other investigators involved in this study disclosed relationships with numerous pharmaceutical companies.

jensmith@mdedge.com

SOURCE: Hashimoto H et al. ASCO 2019. Abstract 11503.

CHICAGO – Olanzapine plus aprepitant, palonosetron, and dexamethasone (APD) can be considered a new standard antiemetic therapy for patients receiving cisplatin-based chemotherapy, according to a speaker at the annual meeting of the American Society for Clinical Oncology.

A 5 mg dose of olanzapine plus APD produced significantly higher complete response (CR) rates than APD plus placebo in a phase 3 trial, said Hironobu Hashimoto, BPharm, of the National Cancer Center Hospital in Tokyo.

In addition, olanzapine plus APD had a significantly longer time to treatment failure and produced higher rates of complete control and total control. However, rates of somnolence, dizziness, and dry mouth were significantly higher with olanzapine plus APD.

In the phase 3 J-FORCE study, Mr. Hashimoto and his colleagues evaluated olanzapine at 5 mg plus standard antiemetic therapy (APD) for the prevention of chemotherapy-induced nausea and vomiting.

The trial enrolled 710 patients, ages 22-75 years, who had malignant solid tumors and were receiving cisplatin-based chemotherapy for the first time. The patients were randomized to olanzapine plus APD or APD plus placebo.

There were 354 patients evaluable for efficacy in the olanzapine arm and 351 in the placebo arm. The primary endpoint was CR, which was defined as no vomiting and no rescue medications, in the delayed phase (24 hours to 120 hours).

The CR rate in the delayed phase was 79% in the olanzapine arm and 66% in the placebo arm (P less than .001). The CR rate in the acute phase (0 to 24 hours) was 95% and 89%, respectively (P equal to .002), and the overall CR rate was 78% and 64%, respectively (P less than .001).

The time to treatment failure was significantly longer in the olanzapine arm (P less than .001).

The rate of complete control in the overall period (0 to 120 hours) was 76% in the olanzapine arm and 61% in the placebo arm (P less than .001). Complete control was defined as no emesis, no rescue medication, and no nausea or low-grade nausea.

The rate of total control in the overall period was 59% in the olanzapine arm and 48% in the placebo arm (P = .005). Total control was defined as no emesis, no rescue medication, and no nausea.

Treatment-related adverse events (in the olanzapine and placebo arms, respectively) included constipation (15% and 11%), hiccups (10% and 6%), somnolence (43% and 33%), insomnia (5% and 7%), dizziness (8% and 3%), and dry mouth (21% and 9%).

Adverse events that occurred significantly more often with olanzapine were somnolence (P = .011), dizziness (P = .004), and dry mouth (P  less than .001).

This study was sponsored by the Japan Agency for Medical Research and Development (AMED). Mr. Hashimoto said he had nothing to disclose. Other investigators involved in this study disclosed relationships with numerous pharmaceutical companies.

jensmith@mdedge.com

SOURCE: Hashimoto H et al. ASCO 2019. Abstract 11503.

CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.

The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.

That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.

“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”

Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.

“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”

Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.

The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.

“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.

Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.

There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.

The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.

“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”

Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.

The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.

SOURCE: Westin J et al. ASCO 2019, Abstract 7508.

CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.

The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.

That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.

“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”

Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.

“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”

Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.

The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.

“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.

Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.

There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.

The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.

“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”

Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.

The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.

SOURCE: Westin J et al. ASCO 2019, Abstract 7508.

CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.

The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.

That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.

“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”

Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.

“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”

Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.

The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.

“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.

Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.

There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.

The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.

“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”

Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.

The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.

SOURCE: Westin J et al. ASCO 2019, Abstract 7508.

CHICAGO – A fixed-duration venetoclax-obinutuzumab regimen is safe and provides a superior outcome versus standard chlorambucil-obinutuzumab in elderly patients with untreated chronic lymphocytic leukemia (CLL) and comorbidities, results of a randomized phase 3 trial showed.

At 24 months, progression-free survival was 88.2% for the venetoclax-obinutuzumab regimen, versus 64.1% for chlorambucil-obinutuzumab (hazard ratio, 0.35; 95% confidence interval, 0.23-0.53; P less than .0001) in CLL-14, an open-label, multinational trial presented at the annual meeting of the American Society of Clinical Oncology.

The regimen, given for just 12 28-day cycles, also achieved the highest rate of minimal residual disease (MRD)-negative responses ever seen in a randomized prospective CLL study, according to investigator Kirsten Fischer, MD, of the University of Cologne in Germany.

“We really think that these unprecedented MRD negativity levels will eventually translate into an improved overall survival,” Dr. Fischer said during an oral abstract presentation.

Matthew Steven Davids, MD, of Dana-Farber Cancer Institute/Harvard Medical School, Boston, said venetoclax plus obinutuzumab offers the potential for 1-year, time-limited therapy, which limits concerns over long-term adherence and has the potential for cost savings, should the therapy prove to be highly durable with further follow-up.

“A limitation of the study is that the comparator arm – chlorambucil plus obinutuzumab – is directly applicable to only a relatively small subset of our older and frailer CLL patients,” Dr. Davids said during a podium discussion of the results.

“But nonetheless, venetoclax plus obinutuzumab is a promising, time-limited regimen, and CLL14 is an immediately practice-changing study for frontline CLL treatment,” he added.

The regimen stands in contrast to ibrutinib, which offers durable responses but requires continuous dosing, and FCR (fludarabine, cyclophosphamide, and rituximab), a time-limited therapy with curative potential that is restricted to younger patients with IGHV-mutated CLL, according to Dr. Davids.

In CLL-14, 432 patients were randomized 1:1 to receive venetoclax-obinutuzumab for six cycles followed by venetoclax for six cycles, or chlorambucil-obinutuzumab for six cycles followed by chlorambucil for six cycles. The median age was 72 years in the venetoclax-obinutuzumab arm and 71 years in the chlorambucil-obinutuzumab arm.

The overall response rate was 85% for venetoclax-obinutuzumab and 71% for chlorambucil-obinutuzumab (P = .0007), Dr. Fischer reported at the meeting.

The improvement in progression-free survival seen in the overall study population was also seen in patients with TP53 deletions or mutations, and in those with unmutated IGHV, Dr. Fischer reported.

Rates of MRD negativity in peripheral blood were 76% versus 35% for the venetoclax- and chlorambucil-containing combinations, respectively (P less than .001), and similarly, MRD negativity in bone marrow was 57% versus 17% (P less than .001), she said.

There were no significant differences in the rates of grade 3 or 4 neutropenia, which occurred in 52.8% of the venetoclax–obinutuzumab treated patients and 48.1% of the chlorambucil-obinutuzumab treated patients, or in grade 3 or 4 infections, which occurred in 17.5% and 15.0%, respectively, according to a report, published simultaneously in the New England Journal of Medicine (2019;380:2225-36).

Likewise, all-cause mortality was not significantly different between the arms, at 9.3% and 7.9%, respectively.

F. Hoffmann-La Roche and AbbVie supported the study. Dr. Fischer reported travel, accommodations, or expenses from Roche in her abstract disclosure.

SOURCE: Fischer K et al. ASCO 2019, Abstract 7502.

CHICAGO – A fixed-duration venetoclax-obinutuzumab regimen is safe and provides a superior outcome versus standard chlorambucil-obinutuzumab in elderly patients with untreated chronic lymphocytic leukemia (CLL) and comorbidities, results of a randomized phase 3 trial showed.

At 24 months, progression-free survival was 88.2% for the venetoclax-obinutuzumab regimen, versus 64.1% for chlorambucil-obinutuzumab (hazard ratio, 0.35; 95% confidence interval, 0.23-0.53; P less than .0001) in CLL-14, an open-label, multinational trial presented at the annual meeting of the American Society of Clinical Oncology.

The regimen, given for just 12 28-day cycles, also achieved the highest rate of minimal residual disease (MRD)-negative responses ever seen in a randomized prospective CLL study, according to investigator Kirsten Fischer, MD, of the University of Cologne in Germany.

“We really think that these unprecedented MRD negativity levels will eventually translate into an improved overall survival,” Dr. Fischer said during an oral abstract presentation.

Matthew Steven Davids, MD, of Dana-Farber Cancer Institute/Harvard Medical School, Boston, said venetoclax plus obinutuzumab offers the potential for 1-year, time-limited therapy, which limits concerns over long-term adherence and has the potential for cost savings, should the therapy prove to be highly durable with further follow-up.

“A limitation of the study is that the comparator arm – chlorambucil plus obinutuzumab – is directly applicable to only a relatively small subset of our older and frailer CLL patients,” Dr. Davids said during a podium discussion of the results.

“But nonetheless, venetoclax plus obinutuzumab is a promising, time-limited regimen, and CLL14 is an immediately practice-changing study for frontline CLL treatment,” he added.

The regimen stands in contrast to ibrutinib, which offers durable responses but requires continuous dosing, and FCR (fludarabine, cyclophosphamide, and rituximab), a time-limited therapy with curative potential that is restricted to younger patients with IGHV-mutated CLL, according to Dr. Davids.

In CLL-14, 432 patients were randomized 1:1 to receive venetoclax-obinutuzumab for six cycles followed by venetoclax for six cycles, or chlorambucil-obinutuzumab for six cycles followed by chlorambucil for six cycles. The median age was 72 years in the venetoclax-obinutuzumab arm and 71 years in the chlorambucil-obinutuzumab arm.

The overall response rate was 85% for venetoclax-obinutuzumab and 71% for chlorambucil-obinutuzumab (P = .0007), Dr. Fischer reported at the meeting.

The improvement in progression-free survival seen in the overall study population was also seen in patients with TP53 deletions or mutations, and in those with unmutated IGHV, Dr. Fischer reported.

Rates of MRD negativity in peripheral blood were 76% versus 35% for the venetoclax- and chlorambucil-containing combinations, respectively (P less than .001), and similarly, MRD negativity in bone marrow was 57% versus 17% (P less than .001), she said.

There were no significant differences in the rates of grade 3 or 4 neutropenia, which occurred in 52.8% of the venetoclax–obinutuzumab treated patients and 48.1% of the chlorambucil-obinutuzumab treated patients, or in grade 3 or 4 infections, which occurred in 17.5% and 15.0%, respectively, according to a report, published simultaneously in the New England Journal of Medicine (2019;380:2225-36).

Likewise, all-cause mortality was not significantly different between the arms, at 9.3% and 7.9%, respectively.

F. Hoffmann-La Roche and AbbVie supported the study. Dr. Fischer reported travel, accommodations, or expenses from Roche in her abstract disclosure.

SOURCE: Fischer K et al. ASCO 2019, Abstract 7502.

CHICAGO – A fixed-duration venetoclax-obinutuzumab regimen is safe and provides a superior outcome versus standard chlorambucil-obinutuzumab in elderly patients with untreated chronic lymphocytic leukemia (CLL) and comorbidities, results of a randomized phase 3 trial showed.

At 24 months, progression-free survival was 88.2% for the venetoclax-obinutuzumab regimen, versus 64.1% for chlorambucil-obinutuzumab (hazard ratio, 0.35; 95% confidence interval, 0.23-0.53; P less than .0001) in CLL-14, an open-label, multinational trial presented at the annual meeting of the American Society of Clinical Oncology.

The regimen, given for just 12 28-day cycles, also achieved the highest rate of minimal residual disease (MRD)-negative responses ever seen in a randomized prospective CLL study, according to investigator Kirsten Fischer, MD, of the University of Cologne in Germany.

“We really think that these unprecedented MRD negativity levels will eventually translate into an improved overall survival,” Dr. Fischer said during an oral abstract presentation.

Matthew Steven Davids, MD, of Dana-Farber Cancer Institute/Harvard Medical School, Boston, said venetoclax plus obinutuzumab offers the potential for 1-year, time-limited therapy, which limits concerns over long-term adherence and has the potential for cost savings, should the therapy prove to be highly durable with further follow-up.

“A limitation of the study is that the comparator arm – chlorambucil plus obinutuzumab – is directly applicable to only a relatively small subset of our older and frailer CLL patients,” Dr. Davids said during a podium discussion of the results.

“But nonetheless, venetoclax plus obinutuzumab is a promising, time-limited regimen, and CLL14 is an immediately practice-changing study for frontline CLL treatment,” he added.

The regimen stands in contrast to ibrutinib, which offers durable responses but requires continuous dosing, and FCR (fludarabine, cyclophosphamide, and rituximab), a time-limited therapy with curative potential that is restricted to younger patients with IGHV-mutated CLL, according to Dr. Davids.

In CLL-14, 432 patients were randomized 1:1 to receive venetoclax-obinutuzumab for six cycles followed by venetoclax for six cycles, or chlorambucil-obinutuzumab for six cycles followed by chlorambucil for six cycles. The median age was 72 years in the venetoclax-obinutuzumab arm and 71 years in the chlorambucil-obinutuzumab arm.

The overall response rate was 85% for venetoclax-obinutuzumab and 71% for chlorambucil-obinutuzumab (P = .0007), Dr. Fischer reported at the meeting.

The improvement in progression-free survival seen in the overall study population was also seen in patients with TP53 deletions or mutations, and in those with unmutated IGHV, Dr. Fischer reported.

Rates of MRD negativity in peripheral blood were 76% versus 35% for the venetoclax- and chlorambucil-containing combinations, respectively (P less than .001), and similarly, MRD negativity in bone marrow was 57% versus 17% (P less than .001), she said.

There were no significant differences in the rates of grade 3 or 4 neutropenia, which occurred in 52.8% of the venetoclax–obinutuzumab treated patients and 48.1% of the chlorambucil-obinutuzumab treated patients, or in grade 3 or 4 infections, which occurred in 17.5% and 15.0%, respectively, according to a report, published simultaneously in the New England Journal of Medicine (2019;380:2225-36).

Likewise, all-cause mortality was not significantly different between the arms, at 9.3% and 7.9%, respectively.

F. Hoffmann-La Roche and AbbVie supported the study. Dr. Fischer reported travel, accommodations, or expenses from Roche in her abstract disclosure.

SOURCE: Fischer K et al. ASCO 2019, Abstract 7502.

CHICAGO – The oral tyrosine kinase inhibitor (TKI) repotrectinib is safe and has demonstrated encouraging activity in patients with advanced ROS1 fusion-positive non-small cell lung cancer, early results of a phase 1/2 study show.

Objective response rates of 82% in 11 TKI-naive patients and 39% in 22 TKI-pretreated patients were seen after treatment with repotrectinib, a next-generation inhibitor of ROS1/TRK/ALK with a 90-fold greater potency for ROS1 versus crizotinib, according to an investigator in the study.

“The TRIDENT-1 study supports repotrectinib as a potential best-in-class ROS1 agent in advanced non–small cell lung cancer,” said investigator ByoungChul Cho, MD, PhD, of Yonsei Cancer Center in Seoul, South Korea, in a podium presentation at the annual meeting of the American Society of Clinical Oncology.

For the 11 TKI-naive patients, no median duration of response had yet been reached over a median follow-up duration of nearly 17 months, with individual response durations that ranged from 10.9 to 17.7 or more months in the 5 of 9 patients remaining in response, Dr. Cho reported.

“This is exciting, because this is the most promising data presented so far with ROS1 TKI in TKI-naive patient population,” Dr. Cho said.

Repotrectinib also showed a potential to overcome TKI resistance mutations, notably G2032R, which is the most common ROS1 resistance mutation after crizotinib treatment.

All five patients with ROS1 G2032R mutation experienced tumor regression, with a confirmed response rate of 40%, Dr. Cho said.

The TKI was relatively well tolerated with four dose-limiting toxicity events including grade 2-3 dizziness in three cases and grade 3 dyspnea and hypoxia in one case.

Of four grade 5 treatment-emergent adverse events, only one case was possibly related to the treatment, Dr. Cho said.

Based on this tolerability and preliminary activity, the pivotal phase 2 portion of TRIDENT-1 is set to begin in the second half of 2019.

Benjamin Besse, MD, PhD, of Paris-Sud University, Orsay, and Institut Gustave Roussy said these preliminary results were very encouraging.

“If we look at the global picture, repotrectinib is probably today the most potent TKI against ROS1,” Dr. Besse said in a podium discussion of the results. “We don’t know yet if this will translate in an improved progression-free survival.”

Close follow-up of adverse events are warranted in further investigations because of the potency of the drug, he added.

Turning Point Therapeutics sponsored the study. Dr. Cho reported disclosures related to TheraCanVac, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, Janssen, Mogam Institute, MSD, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan.
 

SOURCE: Cho BC et al. ASCO 2019, Abstract 9011.

CHICAGO – The oral tyrosine kinase inhibitor (TKI) repotrectinib is safe and has demonstrated encouraging activity in patients with advanced ROS1 fusion-positive non-small cell lung cancer, early results of a phase 1/2 study show.

Objective response rates of 82% in 11 TKI-naive patients and 39% in 22 TKI-pretreated patients were seen after treatment with repotrectinib, a next-generation inhibitor of ROS1/TRK/ALK with a 90-fold greater potency for ROS1 versus crizotinib, according to an investigator in the study.

“The TRIDENT-1 study supports repotrectinib as a potential best-in-class ROS1 agent in advanced non–small cell lung cancer,” said investigator ByoungChul Cho, MD, PhD, of Yonsei Cancer Center in Seoul, South Korea, in a podium presentation at the annual meeting of the American Society of Clinical Oncology.

For the 11 TKI-naive patients, no median duration of response had yet been reached over a median follow-up duration of nearly 17 months, with individual response durations that ranged from 10.9 to 17.7 or more months in the 5 of 9 patients remaining in response, Dr. Cho reported.

“This is exciting, because this is the most promising data presented so far with ROS1 TKI in TKI-naive patient population,” Dr. Cho said.

Repotrectinib also showed a potential to overcome TKI resistance mutations, notably G2032R, which is the most common ROS1 resistance mutation after crizotinib treatment.

All five patients with ROS1 G2032R mutation experienced tumor regression, with a confirmed response rate of 40%, Dr. Cho said.

The TKI was relatively well tolerated with four dose-limiting toxicity events including grade 2-3 dizziness in three cases and grade 3 dyspnea and hypoxia in one case.

Of four grade 5 treatment-emergent adverse events, only one case was possibly related to the treatment, Dr. Cho said.

Based on this tolerability and preliminary activity, the pivotal phase 2 portion of TRIDENT-1 is set to begin in the second half of 2019.

Benjamin Besse, MD, PhD, of Paris-Sud University, Orsay, and Institut Gustave Roussy said these preliminary results were very encouraging.

“If we look at the global picture, repotrectinib is probably today the most potent TKI against ROS1,” Dr. Besse said in a podium discussion of the results. “We don’t know yet if this will translate in an improved progression-free survival.”

Close follow-up of adverse events are warranted in further investigations because of the potency of the drug, he added.

Turning Point Therapeutics sponsored the study. Dr. Cho reported disclosures related to TheraCanVac, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, Janssen, Mogam Institute, MSD, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan.
 

SOURCE: Cho BC et al. ASCO 2019, Abstract 9011.

CHICAGO – The oral tyrosine kinase inhibitor (TKI) repotrectinib is safe and has demonstrated encouraging activity in patients with advanced ROS1 fusion-positive non-small cell lung cancer, early results of a phase 1/2 study show.

Objective response rates of 82% in 11 TKI-naive patients and 39% in 22 TKI-pretreated patients were seen after treatment with repotrectinib, a next-generation inhibitor of ROS1/TRK/ALK with a 90-fold greater potency for ROS1 versus crizotinib, according to an investigator in the study.

“The TRIDENT-1 study supports repotrectinib as a potential best-in-class ROS1 agent in advanced non–small cell lung cancer,” said investigator ByoungChul Cho, MD, PhD, of Yonsei Cancer Center in Seoul, South Korea, in a podium presentation at the annual meeting of the American Society of Clinical Oncology.

For the 11 TKI-naive patients, no median duration of response had yet been reached over a median follow-up duration of nearly 17 months, with individual response durations that ranged from 10.9 to 17.7 or more months in the 5 of 9 patients remaining in response, Dr. Cho reported.

“This is exciting, because this is the most promising data presented so far with ROS1 TKI in TKI-naive patient population,” Dr. Cho said.

Repotrectinib also showed a potential to overcome TKI resistance mutations, notably G2032R, which is the most common ROS1 resistance mutation after crizotinib treatment.

All five patients with ROS1 G2032R mutation experienced tumor regression, with a confirmed response rate of 40%, Dr. Cho said.

The TKI was relatively well tolerated with four dose-limiting toxicity events including grade 2-3 dizziness in three cases and grade 3 dyspnea and hypoxia in one case.

Of four grade 5 treatment-emergent adverse events, only one case was possibly related to the treatment, Dr. Cho said.

Based on this tolerability and preliminary activity, the pivotal phase 2 portion of TRIDENT-1 is set to begin in the second half of 2019.

Benjamin Besse, MD, PhD, of Paris-Sud University, Orsay, and Institut Gustave Roussy said these preliminary results were very encouraging.

“If we look at the global picture, repotrectinib is probably today the most potent TKI against ROS1,” Dr. Besse said in a podium discussion of the results. “We don’t know yet if this will translate in an improved progression-free survival.”

Close follow-up of adverse events are warranted in further investigations because of the potency of the drug, he added.

Turning Point Therapeutics sponsored the study. Dr. Cho reported disclosures related to TheraCanVac, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, Janssen, Mogam Institute, MSD, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan.
 

SOURCE: Cho BC et al. ASCO 2019, Abstract 9011.

CHICAGO – New data suggest pembrolizumab can increase 5-year overall survival (OS) for patients with advanced non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

In the phase 1b KEYNOTE-001 trial, the 5-year OS rate was 23.2% in treatment-naive patients and 15.5% in previously treated patients. This is in comparison to the 5.5% average 5-year OS rate observed in NSCLC patients who receive standard chemotherapy (Noone AM et al. SEER Cancer Statistics Review, 1975-2015).

“In total, the data confirm that pembrolizumab has the potential to improve long-term outcomes for both treatment-naive and previously treated patients with advanced non–small cell lung cancer,” said Edward B. Garon, MD, of the University of California, Los Angeles.

Dr. Garon and colleagues presented these results in a poster at the annual meeting of the American Society for Clinical Oncology, and the data were simultaneously published in the Journal of Clinical Oncology.

KEYNOTE-001 (NCT01295827) enrolled 550 patients with advanced NSCLC who had received no prior therapy (n = 101) or at least one prior line of therapy (n = 449). Initially, patients received pembrolizumab at varying doses depending on body weight, but the protocol was changed to a single dose of pembrolizumab at 200 mg every 3 weeks.

At a median follow-up of 60.6 months, 100 patients were still alive. Sixty patients had received at least 2 years of pembrolizumab, 14 of whom were treatment-naive at baseline, and 46 of whom were previously treated at baseline.

Five-year OS rates were best among patients who had high PD-L1 expression, which was defined as 50% or greater.

Among treatment-naive patients, the 5-year OS rate was 29.6% in PD-L1–high patients and 15.7% in PD-L1–low patients (expression of 1% to 49%). The median OS was 35.4 months and 19.5 months, respectively.

Among previously treated patients, the 5-year OS rate was 25.0% in PD-L1–high patients, 12.6% in patients with PD-L1 expression of 1%-49%, and 3.5% in patients with PD-L1 expression less than 1%. The median OS was 15.4 months, 8.5 months, and 8.6 months, respectively.

Among patients who received at least 2 years of pembrolizumab, the 5-year OS rate was 78.6% in the treatment-naive group and 75.8% in the previously treated group. The objective response rate was 86% and 91%, respectively. The rate of ongoing response at the data cutoff was 58% and 71%, respectively.

“The safety data did not show any unanticipated late toxicity, which I consider encouraging,” Dr. Garon noted.

He said rates of immune-mediated adverse events were similar at 3 years and 5 years of follow-up. At 5 years, 17% of patients (n = 92) had experienced an immune-related adverse event, the most common of which were hypothyroidism (9%), pneumonitis (5%), and hyperthyroidism (2%).

Dr. Garon disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Genentech, Iovance Biotherapeutics, Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis. KEYNOTE-001 was sponsored by Merck Sharp & Dohme Corp.

jensmith@mdedge.com

SOURCES: Garon E. et al. ASCO 2019, Abstract LBA9015; J Clin Oncol. 2019 June 2. doi: 10.1200/JCO.19.00934
 

CHICAGO – New data suggest pembrolizumab can increase 5-year overall survival (OS) for patients with advanced non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

In the phase 1b KEYNOTE-001 trial, the 5-year OS rate was 23.2% in treatment-naive patients and 15.5% in previously treated patients. This is in comparison to the 5.5% average 5-year OS rate observed in NSCLC patients who receive standard chemotherapy (Noone AM et al. SEER Cancer Statistics Review, 1975-2015).

“In total, the data confirm that pembrolizumab has the potential to improve long-term outcomes for both treatment-naive and previously treated patients with advanced non–small cell lung cancer,” said Edward B. Garon, MD, of the University of California, Los Angeles.

Dr. Garon and colleagues presented these results in a poster at the annual meeting of the American Society for Clinical Oncology, and the data were simultaneously published in the Journal of Clinical Oncology.

KEYNOTE-001 (NCT01295827) enrolled 550 patients with advanced NSCLC who had received no prior therapy (n = 101) or at least one prior line of therapy (n = 449). Initially, patients received pembrolizumab at varying doses depending on body weight, but the protocol was changed to a single dose of pembrolizumab at 200 mg every 3 weeks.

At a median follow-up of 60.6 months, 100 patients were still alive. Sixty patients had received at least 2 years of pembrolizumab, 14 of whom were treatment-naive at baseline, and 46 of whom were previously treated at baseline.

Five-year OS rates were best among patients who had high PD-L1 expression, which was defined as 50% or greater.

Among treatment-naive patients, the 5-year OS rate was 29.6% in PD-L1–high patients and 15.7% in PD-L1–low patients (expression of 1% to 49%). The median OS was 35.4 months and 19.5 months, respectively.

Among previously treated patients, the 5-year OS rate was 25.0% in PD-L1–high patients, 12.6% in patients with PD-L1 expression of 1%-49%, and 3.5% in patients with PD-L1 expression less than 1%. The median OS was 15.4 months, 8.5 months, and 8.6 months, respectively.

Among patients who received at least 2 years of pembrolizumab, the 5-year OS rate was 78.6% in the treatment-naive group and 75.8% in the previously treated group. The objective response rate was 86% and 91%, respectively. The rate of ongoing response at the data cutoff was 58% and 71%, respectively.

“The safety data did not show any unanticipated late toxicity, which I consider encouraging,” Dr. Garon noted.

He said rates of immune-mediated adverse events were similar at 3 years and 5 years of follow-up. At 5 years, 17% of patients (n = 92) had experienced an immune-related adverse event, the most common of which were hypothyroidism (9%), pneumonitis (5%), and hyperthyroidism (2%).

Dr. Garon disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Genentech, Iovance Biotherapeutics, Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis. KEYNOTE-001 was sponsored by Merck Sharp & Dohme Corp.

jensmith@mdedge.com

SOURCES: Garon E. et al. ASCO 2019, Abstract LBA9015; J Clin Oncol. 2019 June 2. doi: 10.1200/JCO.19.00934
 

CHICAGO – New data suggest pembrolizumab can increase 5-year overall survival (OS) for patients with advanced non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

In the phase 1b KEYNOTE-001 trial, the 5-year OS rate was 23.2% in treatment-naive patients and 15.5% in previously treated patients. This is in comparison to the 5.5% average 5-year OS rate observed in NSCLC patients who receive standard chemotherapy (Noone AM et al. SEER Cancer Statistics Review, 1975-2015).

“In total, the data confirm that pembrolizumab has the potential to improve long-term outcomes for both treatment-naive and previously treated patients with advanced non–small cell lung cancer,” said Edward B. Garon, MD, of the University of California, Los Angeles.

Dr. Garon and colleagues presented these results in a poster at the annual meeting of the American Society for Clinical Oncology, and the data were simultaneously published in the Journal of Clinical Oncology.

KEYNOTE-001 (NCT01295827) enrolled 550 patients with advanced NSCLC who had received no prior therapy (n = 101) or at least one prior line of therapy (n = 449). Initially, patients received pembrolizumab at varying doses depending on body weight, but the protocol was changed to a single dose of pembrolizumab at 200 mg every 3 weeks.

At a median follow-up of 60.6 months, 100 patients were still alive. Sixty patients had received at least 2 years of pembrolizumab, 14 of whom were treatment-naive at baseline, and 46 of whom were previously treated at baseline.

Five-year OS rates were best among patients who had high PD-L1 expression, which was defined as 50% or greater.

Among treatment-naive patients, the 5-year OS rate was 29.6% in PD-L1–high patients and 15.7% in PD-L1–low patients (expression of 1% to 49%). The median OS was 35.4 months and 19.5 months, respectively.

Among previously treated patients, the 5-year OS rate was 25.0% in PD-L1–high patients, 12.6% in patients with PD-L1 expression of 1%-49%, and 3.5% in patients with PD-L1 expression less than 1%. The median OS was 15.4 months, 8.5 months, and 8.6 months, respectively.

Among patients who received at least 2 years of pembrolizumab, the 5-year OS rate was 78.6% in the treatment-naive group and 75.8% in the previously treated group. The objective response rate was 86% and 91%, respectively. The rate of ongoing response at the data cutoff was 58% and 71%, respectively.

“The safety data did not show any unanticipated late toxicity, which I consider encouraging,” Dr. Garon noted.

He said rates of immune-mediated adverse events were similar at 3 years and 5 years of follow-up. At 5 years, 17% of patients (n = 92) had experienced an immune-related adverse event, the most common of which were hypothyroidism (9%), pneumonitis (5%), and hyperthyroidism (2%).

Dr. Garon disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Genentech, Iovance Biotherapeutics, Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis. KEYNOTE-001 was sponsored by Merck Sharp & Dohme Corp.

jensmith@mdedge.com

SOURCES: Garon E. et al. ASCO 2019, Abstract LBA9015; J Clin Oncol. 2019 June 2. doi: 10.1200/JCO.19.00934
 

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – While gemcitabine plus nab-paclitaxel did not extend independently assessed disease-free survival versus gemcitabine alone in a phase 3 pancreatic cancer study, overall survival data are “encouraging” thus far, and merit further follow-up, an investigator said at the annual meeting of the American Society of Clinical Oncology.

The APACT trial was the first adjuvant pancreatic cancer trial to use an endpoint of disease-free survival, independently assessed without knowledge of medical or clinical circumstances, said investigator Margaret A. Tempero, MD, director of the UCSF Pancreas Center, San Francisco.

With that specific method of assessment, median disease-free survival was 19.4 months for gemcitabine plus nab-paclitaxel versus 18.8 months for gemcitabine alone, a finding that had a “slight trend” in favor of the combination arm, Dr. Tempero said.

By contrast, a more standard investigator-assessed disease-free survival showed an improvement favoring gemcitabine plus nab-paclitaxel over gemcitabine alone, in line with preliminary overall survival data that also appear to show an advantage for the combination over gemcitabine, according to Dr. Tempero.

“We thought we were introducing more rigor into the trial, but I think we all recognize clinically that it is often difficult to differentiate or distinguish recurrence in the pancreatic bed from postsurgical changes,” she said in a discussion period, “but clearly, this is a lesson learned, and I think that would be helpful for the field going forward in avoiding that endpoint.”

Since the trial was launched, both modified FOLFIRINOX and gemcitabine plus capecitabine have become category 1 recommendations for adjuvant pancreatic cancer in clinical practice guidelines from the National Comprehensive Cancer Network.

The “jury is still out” on whether gemcitabine plus nab-paclitaxel will join that group, said Jiping Wang, MD, PhD, of Dana-Farber Cancer Institute, Boston, who discussed the results of the APACT trial in a podium presentation.

“We are still waiting for the final overall survival result of the APACT trial,” he said. “Hopefully, the nab-paclitaxel/gemcitabine combination provides an alternative treatment, especially for patients with R1 resection who cannot tolerate modified FOLFIRINOX.”

While gemcitabine plus capecitabine is a good choice for patients who aren’t able to tolerate modified FOLFIRINOX, available evidence suggests it may not benefit patients with R1 resection, according to Dr. Wang.

The phase 3 APACT trial included patients with surgically resected pancreatic cancer enrolled at 179 sites in 21 countries. A total of 866 patients were randomized 1:1 to receive gemcitabine plus nab-paclitaxel or gemcitabine alone for six cycles.

While median independently assessed disease-free survival was 19.4 months for gemcitabine/nab-paclitaxel and 18.8 months for gemcitabine (hazard ratio, 0.88; P = .1824), median investigator-assessed disease free survival was 16.6 months versus 13.7 months for those arms, respectively (HR, 0.82; P = .0168), according to reported results.

Median interim overall survival was 40.5 months for gemcitabine/nab-paclitaxel versus 36.2 months for gemcitabine (HR, 0.82; P = .045), though the presenter emphasized that longer follow-up is needed to clarify the role of this combination as adjuvant therapy for pancreatic adenocarcinoma.

“I don’t think it’s wrong in a patient who can’t tolerate modified FOLFIRINOX to use gemcitabine and nab-paclitaxel, but I’m not sure everybody would agree with that,” Dr. Tempero said after being asked in the study discussion period if she would advocate for use of this combination regimen in frail patients.

“I think when we get more mature overall survival data, it will be a lot easier to make those decisions,” she said.

Dr. Tempero reported disclosures related to Abbie, Advance Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, BioPharm Communications, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Ignyta, Immunovia, Merck, Pharmacyclics, Pharmacyte Biotech, and Tocagen.

SOURCE: Tempero MA, et al. ASCO 2019. Abstract 4000.

CHICAGO – While gemcitabine plus nab-paclitaxel did not extend independently assessed disease-free survival versus gemcitabine alone in a phase 3 pancreatic cancer study, overall survival data are “encouraging” thus far, and merit further follow-up, an investigator said at the annual meeting of the American Society of Clinical Oncology.

The APACT trial was the first adjuvant pancreatic cancer trial to use an endpoint of disease-free survival, independently assessed without knowledge of medical or clinical circumstances, said investigator Margaret A. Tempero, MD, director of the UCSF Pancreas Center, San Francisco.

With that specific method of assessment, median disease-free survival was 19.4 months for gemcitabine plus nab-paclitaxel versus 18.8 months for gemcitabine alone, a finding that had a “slight trend” in favor of the combination arm, Dr. Tempero said.

By contrast, a more standard investigator-assessed disease-free survival showed an improvement favoring gemcitabine plus nab-paclitaxel over gemcitabine alone, in line with preliminary overall survival data that also appear to show an advantage for the combination over gemcitabine, according to Dr. Tempero.

“We thought we were introducing more rigor into the trial, but I think we all recognize clinically that it is often difficult to differentiate or distinguish recurrence in the pancreatic bed from postsurgical changes,” she said in a discussion period, “but clearly, this is a lesson learned, and I think that would be helpful for the field going forward in avoiding that endpoint.”

Since the trial was launched, both modified FOLFIRINOX and gemcitabine plus capecitabine have become category 1 recommendations for adjuvant pancreatic cancer in clinical practice guidelines from the National Comprehensive Cancer Network.

The “jury is still out” on whether gemcitabine plus nab-paclitaxel will join that group, said Jiping Wang, MD, PhD, of Dana-Farber Cancer Institute, Boston, who discussed the results of the APACT trial in a podium presentation.

“We are still waiting for the final overall survival result of the APACT trial,” he said. “Hopefully, the nab-paclitaxel/gemcitabine combination provides an alternative treatment, especially for patients with R1 resection who cannot tolerate modified FOLFIRINOX.”

While gemcitabine plus capecitabine is a good choice for patients who aren’t able to tolerate modified FOLFIRINOX, available evidence suggests it may not benefit patients with R1 resection, according to Dr. Wang.

The phase 3 APACT trial included patients with surgically resected pancreatic cancer enrolled at 179 sites in 21 countries. A total of 866 patients were randomized 1:1 to receive gemcitabine plus nab-paclitaxel or gemcitabine alone for six cycles.

While median independently assessed disease-free survival was 19.4 months for gemcitabine/nab-paclitaxel and 18.8 months for gemcitabine (hazard ratio, 0.88; P = .1824), median investigator-assessed disease free survival was 16.6 months versus 13.7 months for those arms, respectively (HR, 0.82; P = .0168), according to reported results.

Median interim overall survival was 40.5 months for gemcitabine/nab-paclitaxel versus 36.2 months for gemcitabine (HR, 0.82; P = .045), though the presenter emphasized that longer follow-up is needed to clarify the role of this combination as adjuvant therapy for pancreatic adenocarcinoma.

“I don’t think it’s wrong in a patient who can’t tolerate modified FOLFIRINOX to use gemcitabine and nab-paclitaxel, but I’m not sure everybody would agree with that,” Dr. Tempero said after being asked in the study discussion period if she would advocate for use of this combination regimen in frail patients.

“I think when we get more mature overall survival data, it will be a lot easier to make those decisions,” she said.

Dr. Tempero reported disclosures related to Abbie, Advance Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, BioPharm Communications, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Ignyta, Immunovia, Merck, Pharmacyclics, Pharmacyte Biotech, and Tocagen.

SOURCE: Tempero MA, et al. ASCO 2019. Abstract 4000.

CHICAGO – While gemcitabine plus nab-paclitaxel did not extend independently assessed disease-free survival versus gemcitabine alone in a phase 3 pancreatic cancer study, overall survival data are “encouraging” thus far, and merit further follow-up, an investigator said at the annual meeting of the American Society of Clinical Oncology.

The APACT trial was the first adjuvant pancreatic cancer trial to use an endpoint of disease-free survival, independently assessed without knowledge of medical or clinical circumstances, said investigator Margaret A. Tempero, MD, director of the UCSF Pancreas Center, San Francisco.

With that specific method of assessment, median disease-free survival was 19.4 months for gemcitabine plus nab-paclitaxel versus 18.8 months for gemcitabine alone, a finding that had a “slight trend” in favor of the combination arm, Dr. Tempero said.

By contrast, a more standard investigator-assessed disease-free survival showed an improvement favoring gemcitabine plus nab-paclitaxel over gemcitabine alone, in line with preliminary overall survival data that also appear to show an advantage for the combination over gemcitabine, according to Dr. Tempero.

“We thought we were introducing more rigor into the trial, but I think we all recognize clinically that it is often difficult to differentiate or distinguish recurrence in the pancreatic bed from postsurgical changes,” she said in a discussion period, “but clearly, this is a lesson learned, and I think that would be helpful for the field going forward in avoiding that endpoint.”

Since the trial was launched, both modified FOLFIRINOX and gemcitabine plus capecitabine have become category 1 recommendations for adjuvant pancreatic cancer in clinical practice guidelines from the National Comprehensive Cancer Network.

The “jury is still out” on whether gemcitabine plus nab-paclitaxel will join that group, said Jiping Wang, MD, PhD, of Dana-Farber Cancer Institute, Boston, who discussed the results of the APACT trial in a podium presentation.

“We are still waiting for the final overall survival result of the APACT trial,” he said. “Hopefully, the nab-paclitaxel/gemcitabine combination provides an alternative treatment, especially for patients with R1 resection who cannot tolerate modified FOLFIRINOX.”

While gemcitabine plus capecitabine is a good choice for patients who aren’t able to tolerate modified FOLFIRINOX, available evidence suggests it may not benefit patients with R1 resection, according to Dr. Wang.

The phase 3 APACT trial included patients with surgically resected pancreatic cancer enrolled at 179 sites in 21 countries. A total of 866 patients were randomized 1:1 to receive gemcitabine plus nab-paclitaxel or gemcitabine alone for six cycles.

While median independently assessed disease-free survival was 19.4 months for gemcitabine/nab-paclitaxel and 18.8 months for gemcitabine (hazard ratio, 0.88; P = .1824), median investigator-assessed disease free survival was 16.6 months versus 13.7 months for those arms, respectively (HR, 0.82; P = .0168), according to reported results.

Median interim overall survival was 40.5 months for gemcitabine/nab-paclitaxel versus 36.2 months for gemcitabine (HR, 0.82; P = .045), though the presenter emphasized that longer follow-up is needed to clarify the role of this combination as adjuvant therapy for pancreatic adenocarcinoma.

“I don’t think it’s wrong in a patient who can’t tolerate modified FOLFIRINOX to use gemcitabine and nab-paclitaxel, but I’m not sure everybody would agree with that,” Dr. Tempero said after being asked in the study discussion period if she would advocate for use of this combination regimen in frail patients.

“I think when we get more mature overall survival data, it will be a lot easier to make those decisions,” she said.

Dr. Tempero reported disclosures related to Abbie, Advance Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, BioPharm Communications, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Ignyta, Immunovia, Merck, Pharmacyclics, Pharmacyte Biotech, and Tocagen.

SOURCE: Tempero MA, et al. ASCO 2019. Abstract 4000.

CHICAGO – While cytoreductive nephrectomy is generally still inadvisable in metastatic renal cell carcinoma patients who require medical therapy, an update of the CARMENA trial suggests the procedure may provide benefit for certain patients.

Patients with only one International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor may benefit from cytoreductive nephrectomy, said CARMENA investigator Arnaud Méjean, MD, PhD, in a presentation at the annual meeting of the American Society of Clinical Oncology.

Among patients in CARMENA treated with nephrectomy plus sunitinib, median overall survival was 31.4 months for those with just one risk factor, and 17.6 months for those with two or more (hazard ratio, 1.68; 95% confidence interval, 1.10-2.57; P = .01), suggesting the procedure was “detrimental” to perform in the presence of multiple risk factors, the investigator said.

By contrast, among patients treated with sunitinib alone, there was no significant difference in median overall survival for patients with one risk factor versus those with two or more risk factors, said Dr. Méjean, who is with the Hôpital Européen Georges-Pompidou and Paris Descartes University.

In another analysis of the data, delayed nephrectomy after initial systemic therapy was associated with long overall survival in good responders, supporting that approach as a “good therapeutic strategy,” he said.

Based on these results, Dr. Méjean told ASCO attendees he would “go back to the operating theater to operate just very selected patients.”

In a podium discussion, Alexander Kutikov, MD, FACS, said CARMENA makes it “undeniable” that up-front cytoreductive therapy should be applied to a “very select group” of patients.

While that select group may be defined as the one IMDC risk factor group, Dr. Kutkov said it is also appropriate to offer cytoreductive nephrectomy to carefully selected patients who do not need immediate systemic therapy.

“If the plan is to observe without systemic therapy, proceed with cytoreductive nephrectomy, and for everybody else, I think we take great caution in offering cytoreductive nephrectomy, because it absolutely can harm,” said Dr. Kutikov, professor and chief of urologic oncology at Fox Chase Cancer Center, Philadelphia.

The CARMENA update confirmed that, in general, cytoreductive nephrectomy should not be the standard of care, according to Dr. Méjean.

With follow-up of 61.5 months, or longer than what was previously reported for the 450-patient trial, cytoreductive nephrectomy followed by sunitinib was again found to be not superior to sunitinib alone, he said. Median overall survival was 15.6 months for the nephrectomy plus sunitinib arm versus 19.8 months for the sunitinib arm, showing that sunitinib alone was noninferior based on the statistical design of the trial (hazard ratio, 0.97; 95% CI, 0.79-1.19, with a fixed upper limit for noninferiority of 1.20).

Dr. Méjean reported disclosures related to Ipsen, Novartis, Pfizer, Bristol-Myers Squibb, Janssen, Sanofi and Roche.

SOURCE: Méjean A et al. ASCO 2019, Abstract 4508.

CHICAGO – While cytoreductive nephrectomy is generally still inadvisable in metastatic renal cell carcinoma patients who require medical therapy, an update of the CARMENA trial suggests the procedure may provide benefit for certain patients.

Patients with only one International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor may benefit from cytoreductive nephrectomy, said CARMENA investigator Arnaud Méjean, MD, PhD, in a presentation at the annual meeting of the American Society of Clinical Oncology.

Among patients in CARMENA treated with nephrectomy plus sunitinib, median overall survival was 31.4 months for those with just one risk factor, and 17.6 months for those with two or more (hazard ratio, 1.68; 95% confidence interval, 1.10-2.57; P = .01), suggesting the procedure was “detrimental” to perform in the presence of multiple risk factors, the investigator said.

By contrast, among patients treated with sunitinib alone, there was no significant difference in median overall survival for patients with one risk factor versus those with two or more risk factors, said Dr. Méjean, who is with the Hôpital Européen Georges-Pompidou and Paris Descartes University.

In another analysis of the data, delayed nephrectomy after initial systemic therapy was associated with long overall survival in good responders, supporting that approach as a “good therapeutic strategy,” he said.

Based on these results, Dr. Méjean told ASCO attendees he would “go back to the operating theater to operate just very selected patients.”

In a podium discussion, Alexander Kutikov, MD, FACS, said CARMENA makes it “undeniable” that up-front cytoreductive therapy should be applied to a “very select group” of patients.

While that select group may be defined as the one IMDC risk factor group, Dr. Kutkov said it is also appropriate to offer cytoreductive nephrectomy to carefully selected patients who do not need immediate systemic therapy.

“If the plan is to observe without systemic therapy, proceed with cytoreductive nephrectomy, and for everybody else, I think we take great caution in offering cytoreductive nephrectomy, because it absolutely can harm,” said Dr. Kutikov, professor and chief of urologic oncology at Fox Chase Cancer Center, Philadelphia.

The CARMENA update confirmed that, in general, cytoreductive nephrectomy should not be the standard of care, according to Dr. Méjean.

With follow-up of 61.5 months, or longer than what was previously reported for the 450-patient trial, cytoreductive nephrectomy followed by sunitinib was again found to be not superior to sunitinib alone, he said. Median overall survival was 15.6 months for the nephrectomy plus sunitinib arm versus 19.8 months for the sunitinib arm, showing that sunitinib alone was noninferior based on the statistical design of the trial (hazard ratio, 0.97; 95% CI, 0.79-1.19, with a fixed upper limit for noninferiority of 1.20).

Dr. Méjean reported disclosures related to Ipsen, Novartis, Pfizer, Bristol-Myers Squibb, Janssen, Sanofi and Roche.

SOURCE: Méjean A et al. ASCO 2019, Abstract 4508.

CHICAGO – While cytoreductive nephrectomy is generally still inadvisable in metastatic renal cell carcinoma patients who require medical therapy, an update of the CARMENA trial suggests the procedure may provide benefit for certain patients.

Patients with only one International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor may benefit from cytoreductive nephrectomy, said CARMENA investigator Arnaud Méjean, MD, PhD, in a presentation at the annual meeting of the American Society of Clinical Oncology.

Among patients in CARMENA treated with nephrectomy plus sunitinib, median overall survival was 31.4 months for those with just one risk factor, and 17.6 months for those with two or more (hazard ratio, 1.68; 95% confidence interval, 1.10-2.57; P = .01), suggesting the procedure was “detrimental” to perform in the presence of multiple risk factors, the investigator said.

By contrast, among patients treated with sunitinib alone, there was no significant difference in median overall survival for patients with one risk factor versus those with two or more risk factors, said Dr. Méjean, who is with the Hôpital Européen Georges-Pompidou and Paris Descartes University.

In another analysis of the data, delayed nephrectomy after initial systemic therapy was associated with long overall survival in good responders, supporting that approach as a “good therapeutic strategy,” he said.

Based on these results, Dr. Méjean told ASCO attendees he would “go back to the operating theater to operate just very selected patients.”

In a podium discussion, Alexander Kutikov, MD, FACS, said CARMENA makes it “undeniable” that up-front cytoreductive therapy should be applied to a “very select group” of patients.

While that select group may be defined as the one IMDC risk factor group, Dr. Kutkov said it is also appropriate to offer cytoreductive nephrectomy to carefully selected patients who do not need immediate systemic therapy.

“If the plan is to observe without systemic therapy, proceed with cytoreductive nephrectomy, and for everybody else, I think we take great caution in offering cytoreductive nephrectomy, because it absolutely can harm,” said Dr. Kutikov, professor and chief of urologic oncology at Fox Chase Cancer Center, Philadelphia.

The CARMENA update confirmed that, in general, cytoreductive nephrectomy should not be the standard of care, according to Dr. Méjean.

With follow-up of 61.5 months, or longer than what was previously reported for the 450-patient trial, cytoreductive nephrectomy followed by sunitinib was again found to be not superior to sunitinib alone, he said. Median overall survival was 15.6 months for the nephrectomy plus sunitinib arm versus 19.8 months for the sunitinib arm, showing that sunitinib alone was noninferior based on the statistical design of the trial (hazard ratio, 0.97; 95% CI, 0.79-1.19, with a fixed upper limit for noninferiority of 1.20).

Dr. Méjean reported disclosures related to Ipsen, Novartis, Pfizer, Bristol-Myers Squibb, Janssen, Sanofi and Roche.

SOURCE: Méjean A et al. ASCO 2019, Abstract 4508.

CHICAGO – Fewer than 1 in 20 adults with cancer enroll in clinical trials, and even when cancer patients are willing to participate in a trial, they are often excluded because of comorbidities, prior therapies, or a host of other factors that could confound results.

But as a team of investigators shows in a proof-of-concept study, more generous exclusion criteria in some trials could nearly double the number of participants. Using retrospective, deidentified electronic health record data from the American Society of Clinical Oncology CancerLinQ Discovery database, R. Donald Harvey, PharmD and colleagues found that when they applied broader inclusion criteria for patients with advanced non–small cell lung cancer (NSCLC), the number of patients who would be eligible for clinical trials nearly doubled from 5,495 to 10,349.

In this video interview from the ASCO annual meeting, Dr. Harvey of the Winship Cancer Institute of Emory University in Atlanta discusses collaborations between the oncology community, federal agencies, and the pharmaceutical industry that could improve clinical trials by safely increasing sample sizes.

The study received funding from ASCO. Dr. Harvey disclosed consulting or advisory roles with and institutional research funding from multiple entities.

CHICAGO – Fewer than 1 in 20 adults with cancer enroll in clinical trials, and even when cancer patients are willing to participate in a trial, they are often excluded because of comorbidities, prior therapies, or a host of other factors that could confound results.

But as a team of investigators shows in a proof-of-concept study, more generous exclusion criteria in some trials could nearly double the number of participants. Using retrospective, deidentified electronic health record data from the American Society of Clinical Oncology CancerLinQ Discovery database, R. Donald Harvey, PharmD and colleagues found that when they applied broader inclusion criteria for patients with advanced non–small cell lung cancer (NSCLC), the number of patients who would be eligible for clinical trials nearly doubled from 5,495 to 10,349.

In this video interview from the ASCO annual meeting, Dr. Harvey of the Winship Cancer Institute of Emory University in Atlanta discusses collaborations between the oncology community, federal agencies, and the pharmaceutical industry that could improve clinical trials by safely increasing sample sizes.

The study received funding from ASCO. Dr. Harvey disclosed consulting or advisory roles with and institutional research funding from multiple entities.

CHICAGO – Fewer than 1 in 20 adults with cancer enroll in clinical trials, and even when cancer patients are willing to participate in a trial, they are often excluded because of comorbidities, prior therapies, or a host of other factors that could confound results.

But as a team of investigators shows in a proof-of-concept study, more generous exclusion criteria in some trials could nearly double the number of participants. Using retrospective, deidentified electronic health record data from the American Society of Clinical Oncology CancerLinQ Discovery database, R. Donald Harvey, PharmD and colleagues found that when they applied broader inclusion criteria for patients with advanced non–small cell lung cancer (NSCLC), the number of patients who would be eligible for clinical trials nearly doubled from 5,495 to 10,349.

In this video interview from the ASCO annual meeting, Dr. Harvey of the Winship Cancer Institute of Emory University in Atlanta discusses collaborations between the oncology community, federal agencies, and the pharmaceutical industry that could improve clinical trials by safely increasing sample sizes.

The study received funding from ASCO. Dr. Harvey disclosed consulting or advisory roles with and institutional research funding from multiple entities.