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Chemoradiotherapy does not improve overall or progression-free survival in patients with advanced pancreatic cancer, compared with chemotherapy alone. Gemcitabine plus erlotinib also does not improve overall or progression-free survival when compared with patients who received only gemcitabine.
“This open-label, randomized clinical trial showed no survival benefit of chemoradiotherapy compared with chemotherapy in patients with locally advanced pancreatic cancer... the addition of erlotinib to gemcitabine, despite excellent adherence (92%), failed to improve survival and yet was associated with increased grade 3 hematologic, digestive, and skin toxicities,” wrote Dr. Pascal Hammel of Beaujon Hospital, France, and associates (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4324).
“This suggests that in patients with locally advanced pancreatic cancer, more efficient systemic treatments are needed to treat any early micrometastatic spread and to downstage tumors,” they said.
Investigators enrolled 449 patients with advanced pancreatic cancer in the international, LAP07 phase III trial; 442 met the demographic criteria and were randomly divided into two groups, 223 of which received gemcitabine and 219 of which received gemcitabine plus erlotinib, during the first of two randomization steps. Patients in both groups received their designated drug regime intravenously for three weeks followed by a one week resting period for a total of four cycles.
During step one, 135 of the 223 patients who received gemcitabine, and 134 of the 219 patients who received gemcitabine plus erlotinib, survived the 16-week period progression free and were eligible for step two randomization; 136 patients were then randomly selected to receive chemotherapy and 133 patients were randomly selected to receive chemoradiotherapy.
After the two randomization steps, 68 patients received gemcitabine with chemotherapy, 68 patients received gemcitabine plus erlotinib with chemotherapy, 67 patients received gemcitabine with chemoradiotherapy, and 66 patients received gemcitabine plus erlotinib with chemoradiotherapy.
By the end of the clinical trial, 379 patients had died and 385 had experienced tumor progression. There was no significant difference in overall survival between patients receiving gemcitabine or gemcitabine plus erlotinib (hazard ratio, 1.19; 95% confidence interval, 0.97-1.45; P = .09), and there was no significant difference in progression-free survival (HR, 1.12; 95% CI, 0.92-1.36; P = .26). Patients who received erlotinib were at a significantly elevated risk for experiencing anemia, neutropenia, diarrhea, and acneiform rash when compared with patients who did not receive erlotinib.
There was no significant difference in overall survival between patients receiving chemotherapy or chemoradiotherapy (HR, 1.03; 95% CI, 0.79-1.34; P = .83), and there was no significant difference in progression-free survival (HR, .78; 95% CI, 0.61-1.01; P = .06).
There was also no significant difference in survival when first-step randomization status was combined with second-randomization status (P = .24).
This study was supported by Roche and the French National Institute of Cancer. Dr. Hammel reported receiving consulting fees from Celgene. Seven of the other thirteen investigators reported receiving personal fees, nonfinancial support, grant support, personal fees, or honoraria from Amgen, Merck Serono, Eli Lilly, Roche, Celgene, Sanofi, Novartis, Integragen, Eisai, Invectys, or Nestle.
On Twitter @jess_craig94
Clinical trials that find no difference between groups never garner as much excitement as trials with positive findings. However, clear negative results chart the path forward by informing the design of next-generation studies and hastening retirement of ineffective therapies.
The results of the LAP07 trial are persuasive that contemporary chemoradiation does not add a survival advantage to chemotherapy alone. However, the heterogeneity in response to both chemotherapy and radiation is unclear. What if any features distinguished tumors resistant to treatment and, conversely, those that responded? What features distinguish tumors with propensity to spread locally versus diffusely? Tumors in the former category stand to benefit from regionally focused treatment such as chemoradiation.
The LAP07 trial is progress, but it does not achieve the goal of precision medicine.
The LAP07 trial contributes important new information to help guide treatment decisions for patients with locally advanced pancreas cancer. Ideally, future pancreatic cancer trials will identify molecular markers that better predict responsiveness to specific treatments including radiation and will allow for more focused approaches to treatment selection. In the meantime, chemoradiation need not constitute an essential component of the therapeutic backbone.
Dr. Deborah Schrag is at the Dana Farber Cancer Institute in Boston. Dr. Schrag made these remarks in an editorial accompanying Dr. Hammel’s report (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4284), and she reported having no conflict of interest disclosures.
Clinical trials that find no difference between groups never garner as much excitement as trials with positive findings. However, clear negative results chart the path forward by informing the design of next-generation studies and hastening retirement of ineffective therapies.
The results of the LAP07 trial are persuasive that contemporary chemoradiation does not add a survival advantage to chemotherapy alone. However, the heterogeneity in response to both chemotherapy and radiation is unclear. What if any features distinguished tumors resistant to treatment and, conversely, those that responded? What features distinguish tumors with propensity to spread locally versus diffusely? Tumors in the former category stand to benefit from regionally focused treatment such as chemoradiation.
The LAP07 trial is progress, but it does not achieve the goal of precision medicine.
The LAP07 trial contributes important new information to help guide treatment decisions for patients with locally advanced pancreas cancer. Ideally, future pancreatic cancer trials will identify molecular markers that better predict responsiveness to specific treatments including radiation and will allow for more focused approaches to treatment selection. In the meantime, chemoradiation need not constitute an essential component of the therapeutic backbone.
Dr. Deborah Schrag is at the Dana Farber Cancer Institute in Boston. Dr. Schrag made these remarks in an editorial accompanying Dr. Hammel’s report (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4284), and she reported having no conflict of interest disclosures.
Clinical trials that find no difference between groups never garner as much excitement as trials with positive findings. However, clear negative results chart the path forward by informing the design of next-generation studies and hastening retirement of ineffective therapies.
The results of the LAP07 trial are persuasive that contemporary chemoradiation does not add a survival advantage to chemotherapy alone. However, the heterogeneity in response to both chemotherapy and radiation is unclear. What if any features distinguished tumors resistant to treatment and, conversely, those that responded? What features distinguish tumors with propensity to spread locally versus diffusely? Tumors in the former category stand to benefit from regionally focused treatment such as chemoradiation.
The LAP07 trial is progress, but it does not achieve the goal of precision medicine.
The LAP07 trial contributes important new information to help guide treatment decisions for patients with locally advanced pancreas cancer. Ideally, future pancreatic cancer trials will identify molecular markers that better predict responsiveness to specific treatments including radiation and will allow for more focused approaches to treatment selection. In the meantime, chemoradiation need not constitute an essential component of the therapeutic backbone.
Dr. Deborah Schrag is at the Dana Farber Cancer Institute in Boston. Dr. Schrag made these remarks in an editorial accompanying Dr. Hammel’s report (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4284), and she reported having no conflict of interest disclosures.
Chemoradiotherapy does not improve overall or progression-free survival in patients with advanced pancreatic cancer, compared with chemotherapy alone. Gemcitabine plus erlotinib also does not improve overall or progression-free survival when compared with patients who received only gemcitabine.
“This open-label, randomized clinical trial showed no survival benefit of chemoradiotherapy compared with chemotherapy in patients with locally advanced pancreatic cancer... the addition of erlotinib to gemcitabine, despite excellent adherence (92%), failed to improve survival and yet was associated with increased grade 3 hematologic, digestive, and skin toxicities,” wrote Dr. Pascal Hammel of Beaujon Hospital, France, and associates (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4324).
“This suggests that in patients with locally advanced pancreatic cancer, more efficient systemic treatments are needed to treat any early micrometastatic spread and to downstage tumors,” they said.
Investigators enrolled 449 patients with advanced pancreatic cancer in the international, LAP07 phase III trial; 442 met the demographic criteria and were randomly divided into two groups, 223 of which received gemcitabine and 219 of which received gemcitabine plus erlotinib, during the first of two randomization steps. Patients in both groups received their designated drug regime intravenously for three weeks followed by a one week resting period for a total of four cycles.
During step one, 135 of the 223 patients who received gemcitabine, and 134 of the 219 patients who received gemcitabine plus erlotinib, survived the 16-week period progression free and were eligible for step two randomization; 136 patients were then randomly selected to receive chemotherapy and 133 patients were randomly selected to receive chemoradiotherapy.
After the two randomization steps, 68 patients received gemcitabine with chemotherapy, 68 patients received gemcitabine plus erlotinib with chemotherapy, 67 patients received gemcitabine with chemoradiotherapy, and 66 patients received gemcitabine plus erlotinib with chemoradiotherapy.
By the end of the clinical trial, 379 patients had died and 385 had experienced tumor progression. There was no significant difference in overall survival between patients receiving gemcitabine or gemcitabine plus erlotinib (hazard ratio, 1.19; 95% confidence interval, 0.97-1.45; P = .09), and there was no significant difference in progression-free survival (HR, 1.12; 95% CI, 0.92-1.36; P = .26). Patients who received erlotinib were at a significantly elevated risk for experiencing anemia, neutropenia, diarrhea, and acneiform rash when compared with patients who did not receive erlotinib.
There was no significant difference in overall survival between patients receiving chemotherapy or chemoradiotherapy (HR, 1.03; 95% CI, 0.79-1.34; P = .83), and there was no significant difference in progression-free survival (HR, .78; 95% CI, 0.61-1.01; P = .06).
There was also no significant difference in survival when first-step randomization status was combined with second-randomization status (P = .24).
This study was supported by Roche and the French National Institute of Cancer. Dr. Hammel reported receiving consulting fees from Celgene. Seven of the other thirteen investigators reported receiving personal fees, nonfinancial support, grant support, personal fees, or honoraria from Amgen, Merck Serono, Eli Lilly, Roche, Celgene, Sanofi, Novartis, Integragen, Eisai, Invectys, or Nestle.
On Twitter @jess_craig94
Chemoradiotherapy does not improve overall or progression-free survival in patients with advanced pancreatic cancer, compared with chemotherapy alone. Gemcitabine plus erlotinib also does not improve overall or progression-free survival when compared with patients who received only gemcitabine.
“This open-label, randomized clinical trial showed no survival benefit of chemoradiotherapy compared with chemotherapy in patients with locally advanced pancreatic cancer... the addition of erlotinib to gemcitabine, despite excellent adherence (92%), failed to improve survival and yet was associated with increased grade 3 hematologic, digestive, and skin toxicities,” wrote Dr. Pascal Hammel of Beaujon Hospital, France, and associates (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4324).
“This suggests that in patients with locally advanced pancreatic cancer, more efficient systemic treatments are needed to treat any early micrometastatic spread and to downstage tumors,” they said.
Investigators enrolled 449 patients with advanced pancreatic cancer in the international, LAP07 phase III trial; 442 met the demographic criteria and were randomly divided into two groups, 223 of which received gemcitabine and 219 of which received gemcitabine plus erlotinib, during the first of two randomization steps. Patients in both groups received their designated drug regime intravenously for three weeks followed by a one week resting period for a total of four cycles.
During step one, 135 of the 223 patients who received gemcitabine, and 134 of the 219 patients who received gemcitabine plus erlotinib, survived the 16-week period progression free and were eligible for step two randomization; 136 patients were then randomly selected to receive chemotherapy and 133 patients were randomly selected to receive chemoradiotherapy.
After the two randomization steps, 68 patients received gemcitabine with chemotherapy, 68 patients received gemcitabine plus erlotinib with chemotherapy, 67 patients received gemcitabine with chemoradiotherapy, and 66 patients received gemcitabine plus erlotinib with chemoradiotherapy.
By the end of the clinical trial, 379 patients had died and 385 had experienced tumor progression. There was no significant difference in overall survival between patients receiving gemcitabine or gemcitabine plus erlotinib (hazard ratio, 1.19; 95% confidence interval, 0.97-1.45; P = .09), and there was no significant difference in progression-free survival (HR, 1.12; 95% CI, 0.92-1.36; P = .26). Patients who received erlotinib were at a significantly elevated risk for experiencing anemia, neutropenia, diarrhea, and acneiform rash when compared with patients who did not receive erlotinib.
There was no significant difference in overall survival between patients receiving chemotherapy or chemoradiotherapy (HR, 1.03; 95% CI, 0.79-1.34; P = .83), and there was no significant difference in progression-free survival (HR, .78; 95% CI, 0.61-1.01; P = .06).
There was also no significant difference in survival when first-step randomization status was combined with second-randomization status (P = .24).
This study was supported by Roche and the French National Institute of Cancer. Dr. Hammel reported receiving consulting fees from Celgene. Seven of the other thirteen investigators reported receiving personal fees, nonfinancial support, grant support, personal fees, or honoraria from Amgen, Merck Serono, Eli Lilly, Roche, Celgene, Sanofi, Novartis, Integragen, Eisai, Invectys, or Nestle.
On Twitter @jess_craig94
FROM JAMA
Key clinical point: Compared with chemotherapy, chemoradiotherapy did not improve survival outcomes in patients with advanced pancreatic cancer. Supplementing gemcitabine with erlotinib also did not improve survival outcomes.
Major finding: There was no significant difference in overall survival between patients receiving gemcitabine or gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09) nor was there a significant difference in progression-free survival (HR, 1.12; 95% CI, 0.92-1.36; P = .26). There was also no significant difference in overall survival between patients receiving chemotherapy or chemoradiotherapy (HR, 1.03; 95% CI, 0.79-1.34; P = .83), and there was no significant difference in progression-free survival (HR, 0.78; 95% CI, 0.61-1.01; P = .06).
Data source: An international, multicenter, open-label, unblinded, randomized phase III clinical trial involving 449 patients with advanced pancreatic cancer.
Disclosures: This study was supported by Roche and the French National Institute of Cancer. Dr. Hammel reported receiving consulting fees from Celgene. Dr. Hammel’s associates reported receiving personal fees, nonfinancial support, grant support, personal fees, or honoraria from Amgen, Merck Serono, Lilly, Roche, Celgene, Sanofi, Novartis, Integragen, Eisai, Invectys, and Nestle.