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ABVD and Stanford V similar for bulky mediastinal Hodgkin’s lymphoma
Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.
The results were published online April 20 in the Journal of Clinical Oncology.
The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).
Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.
At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.
Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).
“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.
“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.
Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.
Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.
Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.
The results were published online April 20 in the Journal of Clinical Oncology.
The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).
Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.
At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.
Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).
“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.
“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.
Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.
Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.
Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.
The results were published online April 20 in the Journal of Clinical Oncology.
The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).
Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.
At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.
Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).
“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.
“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.
Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.
Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: No significant differences in outcomes were observed after treatment with ABVD vs. Stanford V in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma.
Major finding: At a median follow-up of 6.5 years, ABVD and Stanford V resulted in similar numbers of treatment failures (19 vs. 23), complete remission rate (75% vs. 81%), and overall response rate (83% vs. 88%), respectively.
Data source: A subgroup analysis of a phase III trial of patients with stage I or II bulky disease, in which 135 were assigned ABVD and 129 received Stanford V.
Disclosures: Dr. Advani reported receiving research funds from Millennium, Takeda Oncology, Seattle Genetics, Genentech/Roche, Allos Therapeutics, Pharmacyclics, Janssen Pharmaceuticals, Celgene, and Idera Pharmaceuticals. Many of his coauthors reported ties to several industry sources.
Advanced NSCLC responds to nivolumab
The immune checkpoint inhibitor nivolumab generated encouraging response rates and overall survival rates in heavily pretreated patients with non–small cell lung cancer, according to a report published online April 20 in the Journal of Clinical Oncology.
In a phase I multicenter dose escalation trial evaluating nivolumab at 1, 3, and 10 mg/kg in 129 patients, the overall response rate (ORR) across all doses was 17.1% (95% CI, 11.0% to 24.7%), duration of response was 17.0 months (1.4+ to 36.8+), overall survival (OS) was 9.9 months (7.8 to 12.4), and 1-, 2-, and 3-year survival rates were 42%, 24%, and 18%, respectively.
At 3 mg/kg, the dose currently being used for phase III trials, ORR was 24.3% (11.8% to 41.2%), OS was 14.9 months (7.3 to 30.3), and 1-, 2-, and 3-year survival was 56%, 42%, and 27%, respectively.
The ORR in the subgroup of patients who had received three or more prior treatments was 21%, similar to the ORR for the entire population, reported Dr. Scott N. Gettinger of the Yale Cancer Center, New Haven, Conn., and associates (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.58.3708]).
“This differs from chemotherapy, where response rates decrease with subsequent lines of therapy. [Outcomes with nivolumab treatment] surpass expectations of second- and third-line chemotherapies, taking into account the caveats of a phase I dose-escalation/expansion trial design,” the researchers wrote.
Expectations for current second-line chemotherapies for advanced non–small cell lung cancer (NSCLC) are ORRs of 7% to 9%, median OS of about 8 months, and 1-year survival of about 30%.
Treatment-related adverse events of any grade occurred in 71% of patients, most commonly fatigue (24%), decreased appetite (12%), and diarrhea (10%). Grade 3-4 events occurred in 14% of patients, most commonly fatigue (3%). There were three treatment-related deaths, all due to pneumonitis. No clear relationship between pneumonitis occurrence and dose level or treatment duration was observed. Guidelines for early identification and management of pneumonitis are now in place.
Additional phase I, II, and III trials are underway to evaluate nivolumab as well as other therapeutic antibodies directed to the immune checkpoint receptor, programmed death 1 (PD-1), or its ligand (PD-L1). The trials have produced consistently encouraging results in patients with advanced NSCLC.
“Efforts are now focusing on evaluating potential predictive biomarkers, such as tumor expression of PD-L1, to select populations most likely to benefit from antibodies targeting the PD-1 axis,” wrote Dr. Gettinger and his associates.
The immune checkpoint inhibitor nivolumab generated encouraging response rates and overall survival rates in heavily pretreated patients with non–small cell lung cancer, according to a report published online April 20 in the Journal of Clinical Oncology.
In a phase I multicenter dose escalation trial evaluating nivolumab at 1, 3, and 10 mg/kg in 129 patients, the overall response rate (ORR) across all doses was 17.1% (95% CI, 11.0% to 24.7%), duration of response was 17.0 months (1.4+ to 36.8+), overall survival (OS) was 9.9 months (7.8 to 12.4), and 1-, 2-, and 3-year survival rates were 42%, 24%, and 18%, respectively.
At 3 mg/kg, the dose currently being used for phase III trials, ORR was 24.3% (11.8% to 41.2%), OS was 14.9 months (7.3 to 30.3), and 1-, 2-, and 3-year survival was 56%, 42%, and 27%, respectively.
The ORR in the subgroup of patients who had received three or more prior treatments was 21%, similar to the ORR for the entire population, reported Dr. Scott N. Gettinger of the Yale Cancer Center, New Haven, Conn., and associates (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.58.3708]).
“This differs from chemotherapy, where response rates decrease with subsequent lines of therapy. [Outcomes with nivolumab treatment] surpass expectations of second- and third-line chemotherapies, taking into account the caveats of a phase I dose-escalation/expansion trial design,” the researchers wrote.
Expectations for current second-line chemotherapies for advanced non–small cell lung cancer (NSCLC) are ORRs of 7% to 9%, median OS of about 8 months, and 1-year survival of about 30%.
Treatment-related adverse events of any grade occurred in 71% of patients, most commonly fatigue (24%), decreased appetite (12%), and diarrhea (10%). Grade 3-4 events occurred in 14% of patients, most commonly fatigue (3%). There were three treatment-related deaths, all due to pneumonitis. No clear relationship between pneumonitis occurrence and dose level or treatment duration was observed. Guidelines for early identification and management of pneumonitis are now in place.
Additional phase I, II, and III trials are underway to evaluate nivolumab as well as other therapeutic antibodies directed to the immune checkpoint receptor, programmed death 1 (PD-1), or its ligand (PD-L1). The trials have produced consistently encouraging results in patients with advanced NSCLC.
“Efforts are now focusing on evaluating potential predictive biomarkers, such as tumor expression of PD-L1, to select populations most likely to benefit from antibodies targeting the PD-1 axis,” wrote Dr. Gettinger and his associates.
The immune checkpoint inhibitor nivolumab generated encouraging response rates and overall survival rates in heavily pretreated patients with non–small cell lung cancer, according to a report published online April 20 in the Journal of Clinical Oncology.
In a phase I multicenter dose escalation trial evaluating nivolumab at 1, 3, and 10 mg/kg in 129 patients, the overall response rate (ORR) across all doses was 17.1% (95% CI, 11.0% to 24.7%), duration of response was 17.0 months (1.4+ to 36.8+), overall survival (OS) was 9.9 months (7.8 to 12.4), and 1-, 2-, and 3-year survival rates were 42%, 24%, and 18%, respectively.
At 3 mg/kg, the dose currently being used for phase III trials, ORR was 24.3% (11.8% to 41.2%), OS was 14.9 months (7.3 to 30.3), and 1-, 2-, and 3-year survival was 56%, 42%, and 27%, respectively.
The ORR in the subgroup of patients who had received three or more prior treatments was 21%, similar to the ORR for the entire population, reported Dr. Scott N. Gettinger of the Yale Cancer Center, New Haven, Conn., and associates (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.58.3708]).
“This differs from chemotherapy, where response rates decrease with subsequent lines of therapy. [Outcomes with nivolumab treatment] surpass expectations of second- and third-line chemotherapies, taking into account the caveats of a phase I dose-escalation/expansion trial design,” the researchers wrote.
Expectations for current second-line chemotherapies for advanced non–small cell lung cancer (NSCLC) are ORRs of 7% to 9%, median OS of about 8 months, and 1-year survival of about 30%.
Treatment-related adverse events of any grade occurred in 71% of patients, most commonly fatigue (24%), decreased appetite (12%), and diarrhea (10%). Grade 3-4 events occurred in 14% of patients, most commonly fatigue (3%). There were three treatment-related deaths, all due to pneumonitis. No clear relationship between pneumonitis occurrence and dose level or treatment duration was observed. Guidelines for early identification and management of pneumonitis are now in place.
Additional phase I, II, and III trials are underway to evaluate nivolumab as well as other therapeutic antibodies directed to the immune checkpoint receptor, programmed death 1 (PD-1), or its ligand (PD-L1). The trials have produced consistently encouraging results in patients with advanced NSCLC.
“Efforts are now focusing on evaluating potential predictive biomarkers, such as tumor expression of PD-L1, to select populations most likely to benefit from antibodies targeting the PD-1 axis,” wrote Dr. Gettinger and his associates.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Nivolumab monotherapy for advanced, heavily pretreated non–small cell lung cancer (NSCLC) generated outcomes that surpassed expectations for second- and third-line chemotherapies.
Major finding: At 3 mg/kg, ORR was 24%, OS was 14.9 months, and 1-, 2-, and 3-year survival rates were 56%, 45%, and 27%, respectively.
Data source: The phase I multicenter dose escalation trial evaluated nivolumab at 1, 3, and 10 mg/kg in 129 patients, 54% of whom had received at least three prior treatments.
Disclosures: Dr. Gettinger reported receiving research funding from or having consulting or advisory roles with Bristol-Myers Squibb, ARIAD Pharmaceuticals, Genentech, AstraZeneca, Bayer Pharmaceuticals, and Pfizer. Many of his coauthors reported ties to several industry sources.
Chemotherapy and stem-cell transplantation combination appears safe
In a population of patients with hematologic malignancies who refuse blood product transfusions, high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) in the absence of hematopoietic support was shown to be relatively safe, according to a report published online April 13 in the Journal of Clinical Oncology.
From May of 1996 to March of 2014 at Pennsylvania Hospital, 125 Jehovah’s Witness patients with lymphoma (n = 55), multiple myeloma (n = 68), or amyloidosis (n = 2) were treated with HDC and ASCT without transfusion through the use of basic blood management techniques. These techniques included priming pretransplantation hemoglobin with erythropoiesis stimulating agents and intravenous iron, limiting iatrogenic blood loss by minimizing phlebotomy, and controlling or preventing bleeding with hemostatic agents, according to Dr. Patricia Ford and her colleagues at the hospital.
They described the low incidence of bleeding even in the absence of prophylactic platelet transfusions, which, they noted, challenges current American Society of Clinical Oncology guidelines that recommend transfusions at platelet counts less than 10 x 103/mcL. “The absence of major bleeding events observed at platelet counts greater than 5 x 103/mcL … suggests that a transfusion threshold trigger of 5 x 103/mcL may be appropriate in a select patient population,” they wrote (J. Clin. Oncol. 2015 April 13 [doi: 10.1200/JCO.2014.57.9912]).
Among the patients treated with HDC and ASCT, those with multiple myeloma (n = 68) received melphalan 200 mg/m2,and those with lymphoma (n = 55) received carmustine 300mg/m2 day 1, cyclophosphamide 1,500 mg/m2 days 2-5, and VP16 700 mg/m2 per day on days 2-4.
At 100 days post transplantation, 115 patients (92%) were still alive. Treatment-related mortality due to anemia, sepsis, pancytopenia, or cardiac events occurred in six patients (4.8%).
Out of 18 bleeding episodes, 2 were major (one grade 4 hemorrhagic temporal infarction with retinal hemorrhages and one grade 3 GI bleed) and 16 were minor. There were no bleeding-associated fatalities.
Cardiac complications occurred at an unexpectedly high rate of 32% (40 patients) and resulted in three treatment-related deaths. Subsequently, all candidates older than 50 years or at risk for cardiac disease were required to undergo cardiac consultation prior to transplantation. Given the cardiovascular risk associated with this population, in addition to ECHO testing, stress testing in patients with suspected coronary artery disease is recommended, the researchers wrote.
On the basis of the observed low mortality and morbidity, Dr. Ford and her associates suggested that HDC followed by ASCT be offered to certain patients who refuse or who have medical contraindications to transfusions, stating that simple blood management strategies were an effective alternative in select patients.
In a population of patients with hematologic malignancies who refuse blood product transfusions, high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) in the absence of hematopoietic support was shown to be relatively safe, according to a report published online April 13 in the Journal of Clinical Oncology.
From May of 1996 to March of 2014 at Pennsylvania Hospital, 125 Jehovah’s Witness patients with lymphoma (n = 55), multiple myeloma (n = 68), or amyloidosis (n = 2) were treated with HDC and ASCT without transfusion through the use of basic blood management techniques. These techniques included priming pretransplantation hemoglobin with erythropoiesis stimulating agents and intravenous iron, limiting iatrogenic blood loss by minimizing phlebotomy, and controlling or preventing bleeding with hemostatic agents, according to Dr. Patricia Ford and her colleagues at the hospital.
They described the low incidence of bleeding even in the absence of prophylactic platelet transfusions, which, they noted, challenges current American Society of Clinical Oncology guidelines that recommend transfusions at platelet counts less than 10 x 103/mcL. “The absence of major bleeding events observed at platelet counts greater than 5 x 103/mcL … suggests that a transfusion threshold trigger of 5 x 103/mcL may be appropriate in a select patient population,” they wrote (J. Clin. Oncol. 2015 April 13 [doi: 10.1200/JCO.2014.57.9912]).
Among the patients treated with HDC and ASCT, those with multiple myeloma (n = 68) received melphalan 200 mg/m2,and those with lymphoma (n = 55) received carmustine 300mg/m2 day 1, cyclophosphamide 1,500 mg/m2 days 2-5, and VP16 700 mg/m2 per day on days 2-4.
At 100 days post transplantation, 115 patients (92%) were still alive. Treatment-related mortality due to anemia, sepsis, pancytopenia, or cardiac events occurred in six patients (4.8%).
Out of 18 bleeding episodes, 2 were major (one grade 4 hemorrhagic temporal infarction with retinal hemorrhages and one grade 3 GI bleed) and 16 were minor. There were no bleeding-associated fatalities.
Cardiac complications occurred at an unexpectedly high rate of 32% (40 patients) and resulted in three treatment-related deaths. Subsequently, all candidates older than 50 years or at risk for cardiac disease were required to undergo cardiac consultation prior to transplantation. Given the cardiovascular risk associated with this population, in addition to ECHO testing, stress testing in patients with suspected coronary artery disease is recommended, the researchers wrote.
On the basis of the observed low mortality and morbidity, Dr. Ford and her associates suggested that HDC followed by ASCT be offered to certain patients who refuse or who have medical contraindications to transfusions, stating that simple blood management strategies were an effective alternative in select patients.
In a population of patients with hematologic malignancies who refuse blood product transfusions, high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) in the absence of hematopoietic support was shown to be relatively safe, according to a report published online April 13 in the Journal of Clinical Oncology.
From May of 1996 to March of 2014 at Pennsylvania Hospital, 125 Jehovah’s Witness patients with lymphoma (n = 55), multiple myeloma (n = 68), or amyloidosis (n = 2) were treated with HDC and ASCT without transfusion through the use of basic blood management techniques. These techniques included priming pretransplantation hemoglobin with erythropoiesis stimulating agents and intravenous iron, limiting iatrogenic blood loss by minimizing phlebotomy, and controlling or preventing bleeding with hemostatic agents, according to Dr. Patricia Ford and her colleagues at the hospital.
They described the low incidence of bleeding even in the absence of prophylactic platelet transfusions, which, they noted, challenges current American Society of Clinical Oncology guidelines that recommend transfusions at platelet counts less than 10 x 103/mcL. “The absence of major bleeding events observed at platelet counts greater than 5 x 103/mcL … suggests that a transfusion threshold trigger of 5 x 103/mcL may be appropriate in a select patient population,” they wrote (J. Clin. Oncol. 2015 April 13 [doi: 10.1200/JCO.2014.57.9912]).
Among the patients treated with HDC and ASCT, those with multiple myeloma (n = 68) received melphalan 200 mg/m2,and those with lymphoma (n = 55) received carmustine 300mg/m2 day 1, cyclophosphamide 1,500 mg/m2 days 2-5, and VP16 700 mg/m2 per day on days 2-4.
At 100 days post transplantation, 115 patients (92%) were still alive. Treatment-related mortality due to anemia, sepsis, pancytopenia, or cardiac events occurred in six patients (4.8%).
Out of 18 bleeding episodes, 2 were major (one grade 4 hemorrhagic temporal infarction with retinal hemorrhages and one grade 3 GI bleed) and 16 were minor. There were no bleeding-associated fatalities.
Cardiac complications occurred at an unexpectedly high rate of 32% (40 patients) and resulted in three treatment-related deaths. Subsequently, all candidates older than 50 years or at risk for cardiac disease were required to undergo cardiac consultation prior to transplantation. Given the cardiovascular risk associated with this population, in addition to ECHO testing, stress testing in patients with suspected coronary artery disease is recommended, the researchers wrote.
On the basis of the observed low mortality and morbidity, Dr. Ford and her associates suggested that HDC followed by ASCT be offered to certain patients who refuse or who have medical contraindications to transfusions, stating that simple blood management strategies were an effective alternative in select patients.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: In Jehovah’s Witness patients with relapsed lymphoma or multiple myeloma, high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) was safely performed without hematopoietic support.
Major finding: At 100 days post transplantation, 115 patients (92%) were still alive. Treatment-related mortality due to anemia, sepsis, pancytopenia, or cardiac events occurred in six patients (4.8%). Cardiac complications occurred in 40 patients (32%). There were 18 bleeding episodes (2 major, 16 minor), and no bleeding-associated mortality.
Data source: A study of 125 Jehovah’s Witness patients with non-Hodgkin’s lymphoma (n = 36), Hodgkin’s lymphoma (n = 19), multiple myeloma (n = 68), and amyloidosis (n = 2) who were treated with HDC and ASCT without transfusion support.
Disclosures: Dr. Ford and coauthors reported having no disclosures.
Cixutumumab provided no boost to androgen deprivation therapy
Cixutumumab plus androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer produced an insignificant improvement over androgen deprivation alone in undetectable PSA rate after 28 weeks, according to researchers. The report was published online April 6 in the Journal of Clinical Oncology.
After 28 weeks of therapy, 40% of the androgen deprivation (AD) plus cixutumumab arm (42/105) had undetectable PSA compared with 32.3% (34/105) of the AD alone arm (RR, 1.24; one-sided P = .16)
In addition, 35 patients were evaluated for plasma biomarkers hypothesized to be affected by IGF-1R inhibition, but none of the markers were significantly associated with PSA response. “Patients in our trial will continue to be observed for overall survival outcomes, and a prespecified secondary endpoint allows for validation of the undetectable PSA correlation with overall survival. This will be of great interest,” wrote Dr. Evan Yu of University of Washington, Seattle, and associates (J. Clin. Oncol. 2015 April 6 [doi:10.1200/JCO.2014.59.4127]).
“Should the prognostic value of the undetectable PSA model be validated in our trial, future testing of novel therapeutics in the metastatic HSPC setting will be facilitated with this earlier readout,” they said.
The authors chose a short, 28-week endpoint to get an early signal to determine the potential value of a larger phase III trial, and to avoid committing resources and patients to a potentially ineffective therapy.
Preclinical studies using murine xenografts indicated that cixutumumab, a monoclonal antibody specific for insulin-like growth factor 1 receptor (IGF-1R), induces IGF-1R internalization and leads to cancer cell apoptosis in HSPC. However, the xenograft studies may not have adequately modeled the human disease due to the nature of the immunocompromised mouse, intraperitoneal rather than intravenous antibody administration, or the characteristics of the xenograft. Given patient and tumor heterogeneity, multiple xenograft models would provide a more robust model system.
Despite negative results from this trial, Dr. Yu and colleagues wrote, “rationale exists for other combinations with cixutumumab, such as docetaxel or mammalian target of rapamycin inhibitors like temsirolimus.”
Cixutumumab plus androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer produced an insignificant improvement over androgen deprivation alone in undetectable PSA rate after 28 weeks, according to researchers. The report was published online April 6 in the Journal of Clinical Oncology.
After 28 weeks of therapy, 40% of the androgen deprivation (AD) plus cixutumumab arm (42/105) had undetectable PSA compared with 32.3% (34/105) of the AD alone arm (RR, 1.24; one-sided P = .16)
In addition, 35 patients were evaluated for plasma biomarkers hypothesized to be affected by IGF-1R inhibition, but none of the markers were significantly associated with PSA response. “Patients in our trial will continue to be observed for overall survival outcomes, and a prespecified secondary endpoint allows for validation of the undetectable PSA correlation with overall survival. This will be of great interest,” wrote Dr. Evan Yu of University of Washington, Seattle, and associates (J. Clin. Oncol. 2015 April 6 [doi:10.1200/JCO.2014.59.4127]).
“Should the prognostic value of the undetectable PSA model be validated in our trial, future testing of novel therapeutics in the metastatic HSPC setting will be facilitated with this earlier readout,” they said.
The authors chose a short, 28-week endpoint to get an early signal to determine the potential value of a larger phase III trial, and to avoid committing resources and patients to a potentially ineffective therapy.
Preclinical studies using murine xenografts indicated that cixutumumab, a monoclonal antibody specific for insulin-like growth factor 1 receptor (IGF-1R), induces IGF-1R internalization and leads to cancer cell apoptosis in HSPC. However, the xenograft studies may not have adequately modeled the human disease due to the nature of the immunocompromised mouse, intraperitoneal rather than intravenous antibody administration, or the characteristics of the xenograft. Given patient and tumor heterogeneity, multiple xenograft models would provide a more robust model system.
Despite negative results from this trial, Dr. Yu and colleagues wrote, “rationale exists for other combinations with cixutumumab, such as docetaxel or mammalian target of rapamycin inhibitors like temsirolimus.”
Cixutumumab plus androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer produced an insignificant improvement over androgen deprivation alone in undetectable PSA rate after 28 weeks, according to researchers. The report was published online April 6 in the Journal of Clinical Oncology.
After 28 weeks of therapy, 40% of the androgen deprivation (AD) plus cixutumumab arm (42/105) had undetectable PSA compared with 32.3% (34/105) of the AD alone arm (RR, 1.24; one-sided P = .16)
In addition, 35 patients were evaluated for plasma biomarkers hypothesized to be affected by IGF-1R inhibition, but none of the markers were significantly associated with PSA response. “Patients in our trial will continue to be observed for overall survival outcomes, and a prespecified secondary endpoint allows for validation of the undetectable PSA correlation with overall survival. This will be of great interest,” wrote Dr. Evan Yu of University of Washington, Seattle, and associates (J. Clin. Oncol. 2015 April 6 [doi:10.1200/JCO.2014.59.4127]).
“Should the prognostic value of the undetectable PSA model be validated in our trial, future testing of novel therapeutics in the metastatic HSPC setting will be facilitated with this earlier readout,” they said.
The authors chose a short, 28-week endpoint to get an early signal to determine the potential value of a larger phase III trial, and to avoid committing resources and patients to a potentially ineffective therapy.
Preclinical studies using murine xenografts indicated that cixutumumab, a monoclonal antibody specific for insulin-like growth factor 1 receptor (IGF-1R), induces IGF-1R internalization and leads to cancer cell apoptosis in HSPC. However, the xenograft studies may not have adequately modeled the human disease due to the nature of the immunocompromised mouse, intraperitoneal rather than intravenous antibody administration, or the characteristics of the xenograft. Given patient and tumor heterogeneity, multiple xenograft models would provide a more robust model system.
Despite negative results from this trial, Dr. Yu and colleagues wrote, “rationale exists for other combinations with cixutumumab, such as docetaxel or mammalian target of rapamycin inhibitors like temsirolimus.”
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Cixutumumab added to androgen deprivation (AD) therapy did not improve undetectable PSA rate in men with hormone-sensitive prostate cancer.
Major finding: After 28 weeks, undetectable PSA rate was 40% in the cixutumumab-plus-AD group vs. 32.3% in the AD-alone group (relative risk 1.24; one-sided P = .16).
Data source: A multicenter phase II trial that randomized (1:1) 210 patients to receive AD plus cixutumumab or AD alone.
Disclosures: Dr. Yu reported ties with Amgen, Dendreon, Janssen Pharmaceuticals, Medivation, Sanofi-Aventis, Agensys, Astellas Pharma, Bristol-Myers Squibb, GTx, ImClone Systems, Oncogenex, and Genentech/Roche. Many of his coauthors reported ties to several industry sources.
Chronic lymphocytic leukemia prognosis relatively good after transplantation failure
Unlike for those with acute leukemia, patients with chronic lymphocytic leukemia who had disease progression after undergoing transplantation had a relatively good prognosis, with 2- and 5-year overall survival rates of 67% and 38%, investigators reported online April 6 in the Journal of Clinical Oncology.*
Patients with chronic lymphocytic leukemia (CLL) who experienced acute or chronic graft-versus-host disease (GVHD) had significantly longer overall survival (OS) than those who did not have GVHD (P = .04 and P = .05, respectively). “Nearly half our patients with active CLL after transplantation had chronic GVHD, and the association of chronic GVHD with achieving cure and its power to predict OS among patients for whom transplantation failed suggests that the GVL (graft-versus-leukemia) effect contributes to prolonged survival even in patients with a high burden of disease,” wrote Dr. Uri Rozovski and associates at the University of Texas MD Anderson Cancer Center, Houston (J. Clin. Oncol. 2015 Apr. 6 [doi:10.1200/JCO.2014.58.6750]).
A matched-pair analysis showed that patients who underwent allogeneic stem cell transplant (SCT) about the same time and did not relapse also had higher rates of acute and chronic GVHD (P = .004 and P = .011, respectively).
The retrospective review of the Bone Marrow Transplantation Program database identified 358 patients with CLL or RT who underwent SCT from 1998 to 2011. The study evaluated 72 patients who had disease progression at a median 74 months after SCT, most of whom received one to eight lines of treatment after relapse and had a median OS of almost 3 years from the time of progression. Multivariate analysis showed that low hemoglobin levels and the presence of Richter’s transformation (RT) were associated with shorter OS; chronic GVHD and response to the first post-SCT treatment predicted longer OS.
Patients with RT had a worse prognosis, with a median OS of 15 months (95% confidence interval, 2-28 months) and 2- and 5-year survival rates of 36% and 0%. Transplantation carried a significant risk for transformation: 16 (30%) patients with CLL developed RT after allogeneic SCT. Conversely, four patients with RT developed CLL after transplantation.
The authors note that even in patients who did not maintain a durable response, SCT was beneficial. The study cohort received a variety of salvage treatments, and patients who received ibrutinib responded well. “Because of the favorable outcomes with ibrutinib in relapsed/refractory CLL, we believe that ibrutinib might have a role in the treatment of disease progression following transplantation failure,” they wrote.
*Correction, 4/8/2015: A previous version of this article misstated the type of leukemia referenced in the study.
Unlike for those with acute leukemia, patients with chronic lymphocytic leukemia who had disease progression after undergoing transplantation had a relatively good prognosis, with 2- and 5-year overall survival rates of 67% and 38%, investigators reported online April 6 in the Journal of Clinical Oncology.*
Patients with chronic lymphocytic leukemia (CLL) who experienced acute or chronic graft-versus-host disease (GVHD) had significantly longer overall survival (OS) than those who did not have GVHD (P = .04 and P = .05, respectively). “Nearly half our patients with active CLL after transplantation had chronic GVHD, and the association of chronic GVHD with achieving cure and its power to predict OS among patients for whom transplantation failed suggests that the GVL (graft-versus-leukemia) effect contributes to prolonged survival even in patients with a high burden of disease,” wrote Dr. Uri Rozovski and associates at the University of Texas MD Anderson Cancer Center, Houston (J. Clin. Oncol. 2015 Apr. 6 [doi:10.1200/JCO.2014.58.6750]).
A matched-pair analysis showed that patients who underwent allogeneic stem cell transplant (SCT) about the same time and did not relapse also had higher rates of acute and chronic GVHD (P = .004 and P = .011, respectively).
The retrospective review of the Bone Marrow Transplantation Program database identified 358 patients with CLL or RT who underwent SCT from 1998 to 2011. The study evaluated 72 patients who had disease progression at a median 74 months after SCT, most of whom received one to eight lines of treatment after relapse and had a median OS of almost 3 years from the time of progression. Multivariate analysis showed that low hemoglobin levels and the presence of Richter’s transformation (RT) were associated with shorter OS; chronic GVHD and response to the first post-SCT treatment predicted longer OS.
Patients with RT had a worse prognosis, with a median OS of 15 months (95% confidence interval, 2-28 months) and 2- and 5-year survival rates of 36% and 0%. Transplantation carried a significant risk for transformation: 16 (30%) patients with CLL developed RT after allogeneic SCT. Conversely, four patients with RT developed CLL after transplantation.
The authors note that even in patients who did not maintain a durable response, SCT was beneficial. The study cohort received a variety of salvage treatments, and patients who received ibrutinib responded well. “Because of the favorable outcomes with ibrutinib in relapsed/refractory CLL, we believe that ibrutinib might have a role in the treatment of disease progression following transplantation failure,” they wrote.
*Correction, 4/8/2015: A previous version of this article misstated the type of leukemia referenced in the study.
Unlike for those with acute leukemia, patients with chronic lymphocytic leukemia who had disease progression after undergoing transplantation had a relatively good prognosis, with 2- and 5-year overall survival rates of 67% and 38%, investigators reported online April 6 in the Journal of Clinical Oncology.*
Patients with chronic lymphocytic leukemia (CLL) who experienced acute or chronic graft-versus-host disease (GVHD) had significantly longer overall survival (OS) than those who did not have GVHD (P = .04 and P = .05, respectively). “Nearly half our patients with active CLL after transplantation had chronic GVHD, and the association of chronic GVHD with achieving cure and its power to predict OS among patients for whom transplantation failed suggests that the GVL (graft-versus-leukemia) effect contributes to prolonged survival even in patients with a high burden of disease,” wrote Dr. Uri Rozovski and associates at the University of Texas MD Anderson Cancer Center, Houston (J. Clin. Oncol. 2015 Apr. 6 [doi:10.1200/JCO.2014.58.6750]).
A matched-pair analysis showed that patients who underwent allogeneic stem cell transplant (SCT) about the same time and did not relapse also had higher rates of acute and chronic GVHD (P = .004 and P = .011, respectively).
The retrospective review of the Bone Marrow Transplantation Program database identified 358 patients with CLL or RT who underwent SCT from 1998 to 2011. The study evaluated 72 patients who had disease progression at a median 74 months after SCT, most of whom received one to eight lines of treatment after relapse and had a median OS of almost 3 years from the time of progression. Multivariate analysis showed that low hemoglobin levels and the presence of Richter’s transformation (RT) were associated with shorter OS; chronic GVHD and response to the first post-SCT treatment predicted longer OS.
Patients with RT had a worse prognosis, with a median OS of 15 months (95% confidence interval, 2-28 months) and 2- and 5-year survival rates of 36% and 0%. Transplantation carried a significant risk for transformation: 16 (30%) patients with CLL developed RT after allogeneic SCT. Conversely, four patients with RT developed CLL after transplantation.
The authors note that even in patients who did not maintain a durable response, SCT was beneficial. The study cohort received a variety of salvage treatments, and patients who received ibrutinib responded well. “Because of the favorable outcomes with ibrutinib in relapsed/refractory CLL, we believe that ibrutinib might have a role in the treatment of disease progression following transplantation failure,” they wrote.
*Correction, 4/8/2015: A previous version of this article misstated the type of leukemia referenced in the study.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The prognosis for patients with chronic lymphocytic* leukemia who have undergone failed stem cell transplantation (SCT) is relatively good.
Major finding: From the time of progression after SCT, median OS was 36 months (95% CI, 24-48) for patients with CLL, and 38% survived 5 or more years.
Data source: The retrospective database review identified 72 patients with CLL or Richter’s transformation who underwent allogenic SCT from 1998 to 2011 and progressed after transplantation.
Disclosures: Dr. Rozovski reported having no disclosures. Two of the coauthors reported ties to several industry sources.
Circulating tumor cells and LDH level provide surrogate for survival in advanced prostate cancer
A biomarker panel of circulating tumor cell count plus lactate dehydrogenase level met criteria as a surrogate for overall survival in individual patients with castration-resistant prostate cancer, according to research published online March 23 in the Journal of Clinical Oncology.
Recent progress in prostate cancer therapy has created the need for reliable post-treatment outcome measures that are surrogates for survival to guide patient management and to aid in the regulatory approval process. Investigators sought to identify an efficacy-response surrogate, to be confirmed in future trials, within the phase III clinical trial for abiraterone acetate plus prednisone vs. prednisone alone for patients with castration-resistant prostate cancer.
“Such a surrogate would shorten drug development times and eliminate the potential confounding effects of post protocol therapy on survival,” wrote Dr. Howard I Scher, head of the genitourinary oncology service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan Kettering Cancer Center, New York, and associates.
The trial’s primary endpoint, overall survival, was significantly greater in patients who received abiraterone acetate plus prednisone vs prednisone alone (17.7 vs. 15.1 months, respectively, P = .035). This finding laid the foundation to evaluate a surrogate endpoint for survival according to the Prentice criteria, Dr. Scher and his associates wrote (J. Clin. Onc. 2015 March 23 [doi:10.1200/JCO.2014.55.3487]).
The four Prentice criteria for individual patient-level surrogacy are that the treatment has significant effects on the endpoint as well as the biomarker, the biomarker effects the endpoint, and the effect of the treatment on the endpoint is captured by the biomarker.
Measured at 12 weeks, circulating tumor cell (CTC) count and lactate dehydrogenase (LDH) level were used to categorize the 711 patients as low risk (CTC < 5 cells/7.5 mL of blood; any LDH), medium risk (CTC greater than or equal to 5 cells/7.5 mL of blood; LDH less than or equal to 250 U/L), and high risk (CTC greater than or equal to 5 cells/7.5 mL of blood; LDH > 250 U/L). Patients classified as low risk had 1- and 2-year survival of 82% and 46%, compared with 25% and 2% for patients classified as high risk by the surrogate.
The biomarker panel of CTC count plus LDH level satisfied the four Prentice criteria, thereby demonstrating individual patient-level surrogacy and supporting its use as a clinical trial endpoint. Other ongoing phase III trials will generate evidence to validate the surrogacy, the authors said.
A biomarker panel of circulating tumor cell count plus lactate dehydrogenase level met criteria as a surrogate for overall survival in individual patients with castration-resistant prostate cancer, according to research published online March 23 in the Journal of Clinical Oncology.
Recent progress in prostate cancer therapy has created the need for reliable post-treatment outcome measures that are surrogates for survival to guide patient management and to aid in the regulatory approval process. Investigators sought to identify an efficacy-response surrogate, to be confirmed in future trials, within the phase III clinical trial for abiraterone acetate plus prednisone vs. prednisone alone for patients with castration-resistant prostate cancer.
“Such a surrogate would shorten drug development times and eliminate the potential confounding effects of post protocol therapy on survival,” wrote Dr. Howard I Scher, head of the genitourinary oncology service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan Kettering Cancer Center, New York, and associates.
The trial’s primary endpoint, overall survival, was significantly greater in patients who received abiraterone acetate plus prednisone vs prednisone alone (17.7 vs. 15.1 months, respectively, P = .035). This finding laid the foundation to evaluate a surrogate endpoint for survival according to the Prentice criteria, Dr. Scher and his associates wrote (J. Clin. Onc. 2015 March 23 [doi:10.1200/JCO.2014.55.3487]).
The four Prentice criteria for individual patient-level surrogacy are that the treatment has significant effects on the endpoint as well as the biomarker, the biomarker effects the endpoint, and the effect of the treatment on the endpoint is captured by the biomarker.
Measured at 12 weeks, circulating tumor cell (CTC) count and lactate dehydrogenase (LDH) level were used to categorize the 711 patients as low risk (CTC < 5 cells/7.5 mL of blood; any LDH), medium risk (CTC greater than or equal to 5 cells/7.5 mL of blood; LDH less than or equal to 250 U/L), and high risk (CTC greater than or equal to 5 cells/7.5 mL of blood; LDH > 250 U/L). Patients classified as low risk had 1- and 2-year survival of 82% and 46%, compared with 25% and 2% for patients classified as high risk by the surrogate.
The biomarker panel of CTC count plus LDH level satisfied the four Prentice criteria, thereby demonstrating individual patient-level surrogacy and supporting its use as a clinical trial endpoint. Other ongoing phase III trials will generate evidence to validate the surrogacy, the authors said.
A biomarker panel of circulating tumor cell count plus lactate dehydrogenase level met criteria as a surrogate for overall survival in individual patients with castration-resistant prostate cancer, according to research published online March 23 in the Journal of Clinical Oncology.
Recent progress in prostate cancer therapy has created the need for reliable post-treatment outcome measures that are surrogates for survival to guide patient management and to aid in the regulatory approval process. Investigators sought to identify an efficacy-response surrogate, to be confirmed in future trials, within the phase III clinical trial for abiraterone acetate plus prednisone vs. prednisone alone for patients with castration-resistant prostate cancer.
“Such a surrogate would shorten drug development times and eliminate the potential confounding effects of post protocol therapy on survival,” wrote Dr. Howard I Scher, head of the genitourinary oncology service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan Kettering Cancer Center, New York, and associates.
The trial’s primary endpoint, overall survival, was significantly greater in patients who received abiraterone acetate plus prednisone vs prednisone alone (17.7 vs. 15.1 months, respectively, P = .035). This finding laid the foundation to evaluate a surrogate endpoint for survival according to the Prentice criteria, Dr. Scher and his associates wrote (J. Clin. Onc. 2015 March 23 [doi:10.1200/JCO.2014.55.3487]).
The four Prentice criteria for individual patient-level surrogacy are that the treatment has significant effects on the endpoint as well as the biomarker, the biomarker effects the endpoint, and the effect of the treatment on the endpoint is captured by the biomarker.
Measured at 12 weeks, circulating tumor cell (CTC) count and lactate dehydrogenase (LDH) level were used to categorize the 711 patients as low risk (CTC < 5 cells/7.5 mL of blood; any LDH), medium risk (CTC greater than or equal to 5 cells/7.5 mL of blood; LDH less than or equal to 250 U/L), and high risk (CTC greater than or equal to 5 cells/7.5 mL of blood; LDH > 250 U/L). Patients classified as low risk had 1- and 2-year survival of 82% and 46%, compared with 25% and 2% for patients classified as high risk by the surrogate.
The biomarker panel of CTC count plus LDH level satisfied the four Prentice criteria, thereby demonstrating individual patient-level surrogacy and supporting its use as a clinical trial endpoint. Other ongoing phase III trials will generate evidence to validate the surrogacy, the authors said.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: A biomarker panel of circulating tumor cell count and lactate dehydrogenase level provided a surrogate measure for overall survival in patients with advanced prostate cancer.
Major finding: For patients classified as low risk, the 1- and 2-year survival was 82% and 46% vs. 25% and 2% for patients classified as high risk by the surrogate.
Data source: As a secondary objective to the randomized, double-blind phase III trial of abiraterone acetate for patients with previously treated metastatic castration-resistant prostate cancer, 711 patients were evaluated at 12 weeks for biomarkers as survival surrogates.
Disclosures: Dr. Scher and many of his coauthors reported having consulting or advisory roles with several industry sources. This research was supported by Cougar Biotechnology (now Janssen Oncology) and Veridex (now Janssen Diagnostics).
Nivolumab benefits patients with previously treated renal cell carcinoma
After a median follow-up of 45 months, the anti–PD-1 antibody nivolumab showed benefit in a majority of patients who had previously received one to five treatments for renal cell carcinoma, according to a report published online March 23 in the Journal of Clinical Oncology.
The previously treated cohort included 71% who had received two prior systemic treatments and 44% who had received three or more prior treatments for renal cell carcinoma (RCC). Out of the total 34 patients, 10 (29%) had objective responses, nine (27%) had stable disease for at least 24 weeks, 2 (6%) had stable disease for at least 48 weeks, and 3 patients (9%) had unconventional immune-related responses, which can include reduction in target lesions in the presence of new lesions or regression after initial progression (J. Clin. Oncol. 2015 Mar. 23 [doi:10.1200/JCO.2014.58.1041]).
“The results of our study suggest that nivolumab can be administered safely in an outpatient setting to pretreated patients with RCC and demonstrate durable clinical activity. Blockade of the PD-1 pathway may represent an important new target for RCC therapy,” wrote Dr. David F. McDermott of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, and his colleagues.
Adverse events of any grade were experienced by 29 (85%) patients, and 6 patients had grade 3-4 events. The toxicities, the most frequent of which were fatigue (14), rash (9), diarrhea (6), and pruritus (6), were consistent with immune-related mechanisms. The investigators noted that the favorable safety profile may permit the antibody to be used in combination and adjuvant regimens.
Patients received intravenous nivolumab 1 mg/kg (18 patients) or 10 mg/kg (16 patients) in an outpatient setting twice per week for up to 96 weeks. Some degree of tumor shrinkage occurred in 20 of 34 patients. Among the 10 patients with objective responses, the median duration was 12.9 months (range, 8.4-29.1+ months, with four responses ongoing at the time of analysis). Overall survival rates at 1, 2, and 3 years were 71%, 48%, and 44%, respectively, and the median overall survival was 22.4 months.
While the results are encouraging, the authors added that more research to understand the mechanism of action is needed to optimize the use of anti–PD-1 antibodies. Studies have shown that tumor expression of PD-L1 increases the likelihood of benefit from anti–PD-1, but not in all cases.
“A more comprehensive understanding of why some patients with PD-L1–negative tumors respond to PD-1 pathway blockade, while many with PD-L1–positive tumors fail to do so, will be critical to improving patient selection and developing anti–PD-1–based combination strategies for RCC,” they wrote.
Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.
After a median follow-up of 45 months, the anti–PD-1 antibody nivolumab showed benefit in a majority of patients who had previously received one to five treatments for renal cell carcinoma, according to a report published online March 23 in the Journal of Clinical Oncology.
The previously treated cohort included 71% who had received two prior systemic treatments and 44% who had received three or more prior treatments for renal cell carcinoma (RCC). Out of the total 34 patients, 10 (29%) had objective responses, nine (27%) had stable disease for at least 24 weeks, 2 (6%) had stable disease for at least 48 weeks, and 3 patients (9%) had unconventional immune-related responses, which can include reduction in target lesions in the presence of new lesions or regression after initial progression (J. Clin. Oncol. 2015 Mar. 23 [doi:10.1200/JCO.2014.58.1041]).
“The results of our study suggest that nivolumab can be administered safely in an outpatient setting to pretreated patients with RCC and demonstrate durable clinical activity. Blockade of the PD-1 pathway may represent an important new target for RCC therapy,” wrote Dr. David F. McDermott of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, and his colleagues.
Adverse events of any grade were experienced by 29 (85%) patients, and 6 patients had grade 3-4 events. The toxicities, the most frequent of which were fatigue (14), rash (9), diarrhea (6), and pruritus (6), were consistent with immune-related mechanisms. The investigators noted that the favorable safety profile may permit the antibody to be used in combination and adjuvant regimens.
Patients received intravenous nivolumab 1 mg/kg (18 patients) or 10 mg/kg (16 patients) in an outpatient setting twice per week for up to 96 weeks. Some degree of tumor shrinkage occurred in 20 of 34 patients. Among the 10 patients with objective responses, the median duration was 12.9 months (range, 8.4-29.1+ months, with four responses ongoing at the time of analysis). Overall survival rates at 1, 2, and 3 years were 71%, 48%, and 44%, respectively, and the median overall survival was 22.4 months.
While the results are encouraging, the authors added that more research to understand the mechanism of action is needed to optimize the use of anti–PD-1 antibodies. Studies have shown that tumor expression of PD-L1 increases the likelihood of benefit from anti–PD-1, but not in all cases.
“A more comprehensive understanding of why some patients with PD-L1–negative tumors respond to PD-1 pathway blockade, while many with PD-L1–positive tumors fail to do so, will be critical to improving patient selection and developing anti–PD-1–based combination strategies for RCC,” they wrote.
Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.
After a median follow-up of 45 months, the anti–PD-1 antibody nivolumab showed benefit in a majority of patients who had previously received one to five treatments for renal cell carcinoma, according to a report published online March 23 in the Journal of Clinical Oncology.
The previously treated cohort included 71% who had received two prior systemic treatments and 44% who had received three or more prior treatments for renal cell carcinoma (RCC). Out of the total 34 patients, 10 (29%) had objective responses, nine (27%) had stable disease for at least 24 weeks, 2 (6%) had stable disease for at least 48 weeks, and 3 patients (9%) had unconventional immune-related responses, which can include reduction in target lesions in the presence of new lesions or regression after initial progression (J. Clin. Oncol. 2015 Mar. 23 [doi:10.1200/JCO.2014.58.1041]).
“The results of our study suggest that nivolumab can be administered safely in an outpatient setting to pretreated patients with RCC and demonstrate durable clinical activity. Blockade of the PD-1 pathway may represent an important new target for RCC therapy,” wrote Dr. David F. McDermott of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, and his colleagues.
Adverse events of any grade were experienced by 29 (85%) patients, and 6 patients had grade 3-4 events. The toxicities, the most frequent of which were fatigue (14), rash (9), diarrhea (6), and pruritus (6), were consistent with immune-related mechanisms. The investigators noted that the favorable safety profile may permit the antibody to be used in combination and adjuvant regimens.
Patients received intravenous nivolumab 1 mg/kg (18 patients) or 10 mg/kg (16 patients) in an outpatient setting twice per week for up to 96 weeks. Some degree of tumor shrinkage occurred in 20 of 34 patients. Among the 10 patients with objective responses, the median duration was 12.9 months (range, 8.4-29.1+ months, with four responses ongoing at the time of analysis). Overall survival rates at 1, 2, and 3 years were 71%, 48%, and 44%, respectively, and the median overall survival was 22.4 months.
While the results are encouraging, the authors added that more research to understand the mechanism of action is needed to optimize the use of anti–PD-1 antibodies. Studies have shown that tumor expression of PD-L1 increases the likelihood of benefit from anti–PD-1, but not in all cases.
“A more comprehensive understanding of why some patients with PD-L1–negative tumors respond to PD-1 pathway blockade, while many with PD-L1–positive tumors fail to do so, will be critical to improving patient selection and developing anti–PD-1–based combination strategies for RCC,” they wrote.
Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: A majority of previously treated patients with renal cell carcinoma benefited from nivolumab.
Major finding: At a median 45-month follow-up, 29% of patients had objective responses, 27% had stable disease, and 9% had developed unconventional immune-related responses.
Data source: From 2008 to 2012, 34 patients received intravenous nivolumab, 1 or 10 mg/kg, twice per week for up to 96 weeks.
Disclosures: Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.
Blood urea nitrogen level and Khorana score predict early pancreatic cancer mortality
Using parameters routinely collected in patients with pancreatic cancer, the Khorana score and the blood urea nitrogen (BUN) level were significantly associated with early mortality in patients with pancreatic cancer who underwent surgical resection, according to a report published in the journal Cancer.
Dr. Davendra P.S. Sohal, an oncologist at Cleveland Clinic, and his colleagues stated that by identifying patients with resectable pancreatic adenocarcinoma who are at high risk of early mortality, the parameters “may be used to stratify patients, and ultimately may be used to select high-risk patients for more aggressive therapies in prospective studies” (Cancer 2015 [doi:10.1002/cncr.29298]).
Multivariate analysis showed the risk for early mortality (before 6 months) increased with high-risk Khorana score (hazard ratio, 2.32; 95% confidence interval, 1.04-5.13; P = .039) and elevated blood urea nitrogen (HR, 4.34; 95% CI, 1.84-10.25; P < .001). The authors noted that other key variables, such as TNM classification of malignant tumor staging, were not associated with early mortality.
The study evaluated 334 patients, median age 67 years, who underwent surgical resection of pancreatic adenocarcinoma during 2006-2013 at the Cleveland Clinic. With a median follow-up time of 39.4 months, there were 205 deaths (61%), and median overall survival was 21.3 months. Within 30 days after surgery, 3 (0.9%) deaths occurred, and within 6 months of surgery, 29 (8.7%) deaths occurred. Most tumors were located in the head of the pancreas (73%); most pathologic stages were T3 (67%) and N1 (63%); median Khorana score was 2; 47% of patients had a score ≥ 3; 59% had comorbidities. Some of the patients received preoperative anticancer therapy, making the study population heterogeneous in that respect.
The Khorana score, a measure of venous thromboembolism risk, combines five items: cancer site, platelet count > 350/nL, white blood cell count > 11/nL, hemoglobin <100 g/L, and body mass index (BMI) ≥ 35 kg/m2; Khorana scores of 3 or greater indicate high risk.
A novel finding in patients with pancreatic cancer, elevated BUN levels have been previously linked to poorer prognosis for patients with non–small cell lung cancer and advanced malignancies who were receiving palliative care. Elevated BUN levels may indicate subclinical renal dysfunction or other comorbidities that influence survival.
Univariate analysis in the current study did not find an association between early mortality and BMI, which may be due to the timing of the measurement. Patients may experience cancer-induced weight loss that renders BMI measures falsely low. The association between BMI and decreased survival after pancreatic cancer diagnosis was found previously to be strongest when BMI was taken 18-20 years prior to diagnosis.
The authors note that although perioperative mortality has improved considerably in recent years, there exists a subgroup of patients who experience early recurrence.
“These patients may not benefit from the current standard of care but to our knowledge, little is known regarding how best to identify such patients at high risk of early mortality,” wrote Dr. Sohal and his associates. The current study identifies a simple set of baseline parameters that may allow for “easy targeting of high-risk patients for specific interventions aimed at improving clinical outcomes.”
Dr. Sohal reported having no disclosures. Dr. Khorana has received fees from several industry sources for work outside of the current study.
Using parameters routinely collected in patients with pancreatic cancer, the Khorana score and the blood urea nitrogen (BUN) level were significantly associated with early mortality in patients with pancreatic cancer who underwent surgical resection, according to a report published in the journal Cancer.
Dr. Davendra P.S. Sohal, an oncologist at Cleveland Clinic, and his colleagues stated that by identifying patients with resectable pancreatic adenocarcinoma who are at high risk of early mortality, the parameters “may be used to stratify patients, and ultimately may be used to select high-risk patients for more aggressive therapies in prospective studies” (Cancer 2015 [doi:10.1002/cncr.29298]).
Multivariate analysis showed the risk for early mortality (before 6 months) increased with high-risk Khorana score (hazard ratio, 2.32; 95% confidence interval, 1.04-5.13; P = .039) and elevated blood urea nitrogen (HR, 4.34; 95% CI, 1.84-10.25; P < .001). The authors noted that other key variables, such as TNM classification of malignant tumor staging, were not associated with early mortality.
The study evaluated 334 patients, median age 67 years, who underwent surgical resection of pancreatic adenocarcinoma during 2006-2013 at the Cleveland Clinic. With a median follow-up time of 39.4 months, there were 205 deaths (61%), and median overall survival was 21.3 months. Within 30 days after surgery, 3 (0.9%) deaths occurred, and within 6 months of surgery, 29 (8.7%) deaths occurred. Most tumors were located in the head of the pancreas (73%); most pathologic stages were T3 (67%) and N1 (63%); median Khorana score was 2; 47% of patients had a score ≥ 3; 59% had comorbidities. Some of the patients received preoperative anticancer therapy, making the study population heterogeneous in that respect.
The Khorana score, a measure of venous thromboembolism risk, combines five items: cancer site, platelet count > 350/nL, white blood cell count > 11/nL, hemoglobin <100 g/L, and body mass index (BMI) ≥ 35 kg/m2; Khorana scores of 3 or greater indicate high risk.
A novel finding in patients with pancreatic cancer, elevated BUN levels have been previously linked to poorer prognosis for patients with non–small cell lung cancer and advanced malignancies who were receiving palliative care. Elevated BUN levels may indicate subclinical renal dysfunction or other comorbidities that influence survival.
Univariate analysis in the current study did not find an association between early mortality and BMI, which may be due to the timing of the measurement. Patients may experience cancer-induced weight loss that renders BMI measures falsely low. The association between BMI and decreased survival after pancreatic cancer diagnosis was found previously to be strongest when BMI was taken 18-20 years prior to diagnosis.
The authors note that although perioperative mortality has improved considerably in recent years, there exists a subgroup of patients who experience early recurrence.
“These patients may not benefit from the current standard of care but to our knowledge, little is known regarding how best to identify such patients at high risk of early mortality,” wrote Dr. Sohal and his associates. The current study identifies a simple set of baseline parameters that may allow for “easy targeting of high-risk patients for specific interventions aimed at improving clinical outcomes.”
Dr. Sohal reported having no disclosures. Dr. Khorana has received fees from several industry sources for work outside of the current study.
Using parameters routinely collected in patients with pancreatic cancer, the Khorana score and the blood urea nitrogen (BUN) level were significantly associated with early mortality in patients with pancreatic cancer who underwent surgical resection, according to a report published in the journal Cancer.
Dr. Davendra P.S. Sohal, an oncologist at Cleveland Clinic, and his colleagues stated that by identifying patients with resectable pancreatic adenocarcinoma who are at high risk of early mortality, the parameters “may be used to stratify patients, and ultimately may be used to select high-risk patients for more aggressive therapies in prospective studies” (Cancer 2015 [doi:10.1002/cncr.29298]).
Multivariate analysis showed the risk for early mortality (before 6 months) increased with high-risk Khorana score (hazard ratio, 2.32; 95% confidence interval, 1.04-5.13; P = .039) and elevated blood urea nitrogen (HR, 4.34; 95% CI, 1.84-10.25; P < .001). The authors noted that other key variables, such as TNM classification of malignant tumor staging, were not associated with early mortality.
The study evaluated 334 patients, median age 67 years, who underwent surgical resection of pancreatic adenocarcinoma during 2006-2013 at the Cleveland Clinic. With a median follow-up time of 39.4 months, there were 205 deaths (61%), and median overall survival was 21.3 months. Within 30 days after surgery, 3 (0.9%) deaths occurred, and within 6 months of surgery, 29 (8.7%) deaths occurred. Most tumors were located in the head of the pancreas (73%); most pathologic stages were T3 (67%) and N1 (63%); median Khorana score was 2; 47% of patients had a score ≥ 3; 59% had comorbidities. Some of the patients received preoperative anticancer therapy, making the study population heterogeneous in that respect.
The Khorana score, a measure of venous thromboembolism risk, combines five items: cancer site, platelet count > 350/nL, white blood cell count > 11/nL, hemoglobin <100 g/L, and body mass index (BMI) ≥ 35 kg/m2; Khorana scores of 3 or greater indicate high risk.
A novel finding in patients with pancreatic cancer, elevated BUN levels have been previously linked to poorer prognosis for patients with non–small cell lung cancer and advanced malignancies who were receiving palliative care. Elevated BUN levels may indicate subclinical renal dysfunction or other comorbidities that influence survival.
Univariate analysis in the current study did not find an association between early mortality and BMI, which may be due to the timing of the measurement. Patients may experience cancer-induced weight loss that renders BMI measures falsely low. The association between BMI and decreased survival after pancreatic cancer diagnosis was found previously to be strongest when BMI was taken 18-20 years prior to diagnosis.
The authors note that although perioperative mortality has improved considerably in recent years, there exists a subgroup of patients who experience early recurrence.
“These patients may not benefit from the current standard of care but to our knowledge, little is known regarding how best to identify such patients at high risk of early mortality,” wrote Dr. Sohal and his associates. The current study identifies a simple set of baseline parameters that may allow for “easy targeting of high-risk patients for specific interventions aimed at improving clinical outcomes.”
Dr. Sohal reported having no disclosures. Dr. Khorana has received fees from several industry sources for work outside of the current study.
FROM CANCER
Key clinical point: High Khorana score and elevated blood urea nitrogen predicted early mortality in patients after surgical resection for pancreatic cancer.
Major finding: For patients with elevated blood urea nitrogen, the early mortality hazard ratio was 4.34 (95% CI, 1.84-10.25), and for high-risk Khorana scores, this was 2.32 (1.04-5.13).
Data source: The retrospective cohort study used medical chart data from 334 consecutive patients who underwent surgical resection at the Cleveland Clinic from 2006 to 2013.
Disclosures: Dr. Sohal reported having no disclosures. Dr. Khorana has received fees from several industry sources for work outside of the current study.
Lapatinib inferior to trastuzumab for HER2-positive breast cancer
In patients with human epidermal growth factor receptor 2–positive advanced breast cancer, the combination of lapatinib plus taxane resulted in poorer progression-free survival and more toxicity than trastuzumab plus taxane, according to final clinical trial results reported online March 16 in the Journal of Clinical Oncology.
“Our results support the use of trastuzumab over lapatinib in the HER2 treatment-naive first-line metastatic setting,” wrote Dr. Karen A. Gelmon of the BC Cancer Agency, Vancouver, and her colleagues (J. Clin. Oncol. 2015 Mar. 16 doi:10.1200/JCO.2014.56.9590]).
For patients taking lapatinib plus taxane, the median progression-free survival was 9.0 months vs. 11.3 months for those taking trastuzumab plus taxane (hazard ratio, 1.37; 95% CI, 1.13-1.65; P = .001). Among patients with centrally confirmed HER2-positive disease, those receiving lapatinib had worse overall survival (HR, 1.47; 95% CI, 1.03-2.09; P = .03), the investigators reported.
From 2008 to 2011 the NCIC Clinical Trials Group MA.31 enrolled patients in 21 countries, and evaluated 537 patients with centrally confirmed HER2-postive disease; 61% had an Eastern Cooperative Oncology Group performance status of 0, 82% had no prior anti-HER2 therapy, 70% had no prior taxane therapy, 65% were estrogen-receptor positive, and 42% had metastatic disease at diagnosis. The median follow up was 21.5 months.
Treatment discontinuation because of toxicity was more frequent with lapatinib (15%) than trastuzumab (8%). Grade 3 or 4 rash occurred in 8% of patients in the lapatinib arm, compared with 0% in the trastuzumab group (P < .001). Grade 3 or 4 diarrhea occurred in 19% vs. 1% of the lapatinib and trastuzumab arms, respectively (P < .001).
The authors noted that these results “have implications for the treatment of patients with advanced HER2-positive breast cancer, where dual therapy or newer agents are not available but where the older agents or biosimilars may be available and affordable.”
In patients with human epidermal growth factor receptor 2–positive advanced breast cancer, the combination of lapatinib plus taxane resulted in poorer progression-free survival and more toxicity than trastuzumab plus taxane, according to final clinical trial results reported online March 16 in the Journal of Clinical Oncology.
“Our results support the use of trastuzumab over lapatinib in the HER2 treatment-naive first-line metastatic setting,” wrote Dr. Karen A. Gelmon of the BC Cancer Agency, Vancouver, and her colleagues (J. Clin. Oncol. 2015 Mar. 16 doi:10.1200/JCO.2014.56.9590]).
For patients taking lapatinib plus taxane, the median progression-free survival was 9.0 months vs. 11.3 months for those taking trastuzumab plus taxane (hazard ratio, 1.37; 95% CI, 1.13-1.65; P = .001). Among patients with centrally confirmed HER2-positive disease, those receiving lapatinib had worse overall survival (HR, 1.47; 95% CI, 1.03-2.09; P = .03), the investigators reported.
From 2008 to 2011 the NCIC Clinical Trials Group MA.31 enrolled patients in 21 countries, and evaluated 537 patients with centrally confirmed HER2-postive disease; 61% had an Eastern Cooperative Oncology Group performance status of 0, 82% had no prior anti-HER2 therapy, 70% had no prior taxane therapy, 65% were estrogen-receptor positive, and 42% had metastatic disease at diagnosis. The median follow up was 21.5 months.
Treatment discontinuation because of toxicity was more frequent with lapatinib (15%) than trastuzumab (8%). Grade 3 or 4 rash occurred in 8% of patients in the lapatinib arm, compared with 0% in the trastuzumab group (P < .001). Grade 3 or 4 diarrhea occurred in 19% vs. 1% of the lapatinib and trastuzumab arms, respectively (P < .001).
The authors noted that these results “have implications for the treatment of patients with advanced HER2-positive breast cancer, where dual therapy or newer agents are not available but where the older agents or biosimilars may be available and affordable.”
In patients with human epidermal growth factor receptor 2–positive advanced breast cancer, the combination of lapatinib plus taxane resulted in poorer progression-free survival and more toxicity than trastuzumab plus taxane, according to final clinical trial results reported online March 16 in the Journal of Clinical Oncology.
“Our results support the use of trastuzumab over lapatinib in the HER2 treatment-naive first-line metastatic setting,” wrote Dr. Karen A. Gelmon of the BC Cancer Agency, Vancouver, and her colleagues (J. Clin. Oncol. 2015 Mar. 16 doi:10.1200/JCO.2014.56.9590]).
For patients taking lapatinib plus taxane, the median progression-free survival was 9.0 months vs. 11.3 months for those taking trastuzumab plus taxane (hazard ratio, 1.37; 95% CI, 1.13-1.65; P = .001). Among patients with centrally confirmed HER2-positive disease, those receiving lapatinib had worse overall survival (HR, 1.47; 95% CI, 1.03-2.09; P = .03), the investigators reported.
From 2008 to 2011 the NCIC Clinical Trials Group MA.31 enrolled patients in 21 countries, and evaluated 537 patients with centrally confirmed HER2-postive disease; 61% had an Eastern Cooperative Oncology Group performance status of 0, 82% had no prior anti-HER2 therapy, 70% had no prior taxane therapy, 65% were estrogen-receptor positive, and 42% had metastatic disease at diagnosis. The median follow up was 21.5 months.
Treatment discontinuation because of toxicity was more frequent with lapatinib (15%) than trastuzumab (8%). Grade 3 or 4 rash occurred in 8% of patients in the lapatinib arm, compared with 0% in the trastuzumab group (P < .001). Grade 3 or 4 diarrhea occurred in 19% vs. 1% of the lapatinib and trastuzumab arms, respectively (P < .001).
The authors noted that these results “have implications for the treatment of patients with advanced HER2-positive breast cancer, where dual therapy or newer agents are not available but where the older agents or biosimilars may be available and affordable.”
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Lapatinib is inferior to trastuzumab for treating patients with advanced HER2-positive breast cancer.
Major finding: The median progression-free survival was 9.0 months for lapatinib and 11.3 months for trastuzumab.
Data source: The NCIC Clinical Trials Group MA.31, a randomized, open-label phase III trial that evaluated 537 patients from 21 countries from 2008 to 2011.
Disclosures: Dr. Karen A. Gelmon reported having consulting or advisory roles with Novartis, Roche/Genentech, Pfizer, and GlaxoSmithKline. Many of her coauthors reported ties to several industry sources.
HSCT recipients face increased fracture risk
The risk of fracture among patients who have undergone hematopoietic stem-cell transplantation was seven to nine times higher among recipients aged 45-64 years compared with the age- and sex-matched subjects in the general U.S. population, according to a study published online March 16 in the Journal of Clinical Oncology.
The retrospective chart review followed 7,620 patients who underwent hematopoietic stem-cell transplantation (HSCT) from 1997 to 2011 at the University of Texas MD Anderson Cancer Center for a median 85 months. The researchers found that 8% developed a fracture. Autologous transplant recipients were 45% more likely to have a fracture than were allogeneic transplant recipients (11% vs. 5%). Factors associated with higher risk included age older than 50 years at the time of HSCT, multiple myeloma, solid organ tumors, and autologous HSCT.
“We discovered an increased risk of fracture at almost all ages in both males and females compared with the corresponding U.S. general population. To the best of our knowledge, this study is the first to quantify the increased incidence of fractures in patients with cancer who undergo HSCT,” wrote Dr. Xerxes Pundole and colleagues at the University of Texas MD Anderson Cancer Center, Houston.
The researchers compared the fracture rates of HSCT recipients to those of the U.S. general population using the 1994 National Health Interview (representing 89,100 individuals) and the 2004 National Hospital Discharge Survey (representing 270,000 patients discharged from hospitals).
Female HSCT recipients aged 45-64 years were eight times more likely to develop a fracture than were age-matched females in the general population, and male HSCT recipients aged 45-64 years were seven to nine times more likely to have a fracture than were age-matched males in the general population, the investigators reported (J. Clin. Oncol. 2015 March 16 [doi:10.1200/JCO.2014.57.8195]).
The current study did not assess comorbid conditions, although these likely influence fracture risk. HSCT transplant recipients often undergo intensive chemotherapy, total-body irradiation, and posttransplantation glucocorticoid use, all of which may contribute to bone loss. The authors noted that increased rates of fractures also occur in patients undergoing solid organ (e.g., kidney, liver, and heart) transplantation.
“This similarity suggests that transplantation and the associated supportive therapies administered may play a key role in this increased risk of fracture,” they wrote.
Dr. Pundole reported having no financial disclosures. One author disclosed ties with Takeda Pharmaceuticals, Celgene, Amgen, Alexion Pharmaceuticals, AiCuris, and Actinium Pharmaceuticals.
The risk of fracture among patients who have undergone hematopoietic stem-cell transplantation was seven to nine times higher among recipients aged 45-64 years compared with the age- and sex-matched subjects in the general U.S. population, according to a study published online March 16 in the Journal of Clinical Oncology.
The retrospective chart review followed 7,620 patients who underwent hematopoietic stem-cell transplantation (HSCT) from 1997 to 2011 at the University of Texas MD Anderson Cancer Center for a median 85 months. The researchers found that 8% developed a fracture. Autologous transplant recipients were 45% more likely to have a fracture than were allogeneic transplant recipients (11% vs. 5%). Factors associated with higher risk included age older than 50 years at the time of HSCT, multiple myeloma, solid organ tumors, and autologous HSCT.
“We discovered an increased risk of fracture at almost all ages in both males and females compared with the corresponding U.S. general population. To the best of our knowledge, this study is the first to quantify the increased incidence of fractures in patients with cancer who undergo HSCT,” wrote Dr. Xerxes Pundole and colleagues at the University of Texas MD Anderson Cancer Center, Houston.
The researchers compared the fracture rates of HSCT recipients to those of the U.S. general population using the 1994 National Health Interview (representing 89,100 individuals) and the 2004 National Hospital Discharge Survey (representing 270,000 patients discharged from hospitals).
Female HSCT recipients aged 45-64 years were eight times more likely to develop a fracture than were age-matched females in the general population, and male HSCT recipients aged 45-64 years were seven to nine times more likely to have a fracture than were age-matched males in the general population, the investigators reported (J. Clin. Oncol. 2015 March 16 [doi:10.1200/JCO.2014.57.8195]).
The current study did not assess comorbid conditions, although these likely influence fracture risk. HSCT transplant recipients often undergo intensive chemotherapy, total-body irradiation, and posttransplantation glucocorticoid use, all of which may contribute to bone loss. The authors noted that increased rates of fractures also occur in patients undergoing solid organ (e.g., kidney, liver, and heart) transplantation.
“This similarity suggests that transplantation and the associated supportive therapies administered may play a key role in this increased risk of fracture,” they wrote.
Dr. Pundole reported having no financial disclosures. One author disclosed ties with Takeda Pharmaceuticals, Celgene, Amgen, Alexion Pharmaceuticals, AiCuris, and Actinium Pharmaceuticals.
The risk of fracture among patients who have undergone hematopoietic stem-cell transplantation was seven to nine times higher among recipients aged 45-64 years compared with the age- and sex-matched subjects in the general U.S. population, according to a study published online March 16 in the Journal of Clinical Oncology.
The retrospective chart review followed 7,620 patients who underwent hematopoietic stem-cell transplantation (HSCT) from 1997 to 2011 at the University of Texas MD Anderson Cancer Center for a median 85 months. The researchers found that 8% developed a fracture. Autologous transplant recipients were 45% more likely to have a fracture than were allogeneic transplant recipients (11% vs. 5%). Factors associated with higher risk included age older than 50 years at the time of HSCT, multiple myeloma, solid organ tumors, and autologous HSCT.
“We discovered an increased risk of fracture at almost all ages in both males and females compared with the corresponding U.S. general population. To the best of our knowledge, this study is the first to quantify the increased incidence of fractures in patients with cancer who undergo HSCT,” wrote Dr. Xerxes Pundole and colleagues at the University of Texas MD Anderson Cancer Center, Houston.
The researchers compared the fracture rates of HSCT recipients to those of the U.S. general population using the 1994 National Health Interview (representing 89,100 individuals) and the 2004 National Hospital Discharge Survey (representing 270,000 patients discharged from hospitals).
Female HSCT recipients aged 45-64 years were eight times more likely to develop a fracture than were age-matched females in the general population, and male HSCT recipients aged 45-64 years were seven to nine times more likely to have a fracture than were age-matched males in the general population, the investigators reported (J. Clin. Oncol. 2015 March 16 [doi:10.1200/JCO.2014.57.8195]).
The current study did not assess comorbid conditions, although these likely influence fracture risk. HSCT transplant recipients often undergo intensive chemotherapy, total-body irradiation, and posttransplantation glucocorticoid use, all of which may contribute to bone loss. The authors noted that increased rates of fractures also occur in patients undergoing solid organ (e.g., kidney, liver, and heart) transplantation.
“This similarity suggests that transplantation and the associated supportive therapies administered may play a key role in this increased risk of fracture,” they wrote.
Dr. Pundole reported having no financial disclosures. One author disclosed ties with Takeda Pharmaceuticals, Celgene, Amgen, Alexion Pharmaceuticals, AiCuris, and Actinium Pharmaceuticals.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Patients who underwent hematopoietic stem-cell transplantation were significantly more likely to develop a fracture compared with individuals in the general population.
Major finding: Overall, 8% of patients developed a fracture: 11% after autologous and 5% after allogeneic transplantation.
Data source: A retrospective chart review of 7,620 patients who underwent hematopoietic stem-cell transplantation at the University of Texas MD Anderson Cancer Center from 1997 to 2011.
Disclosures: Dr. Pundole reported having no financial disclosures. One author disclosed ties with Takeda Pharmaceuticals, Celgene, Amgen, Alexion Pharmaceuticals, AiCuris, and Actinium Pharmaceuticals.