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Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
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Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
|
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
|
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
FROM A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Median overall survival in patients with metastatic pancreatic cancer increased from 6.7 months on gemcitabine to 8.5 months on nab-paclitaxel plus gemcitabine.
Data Source: International phase III clinical trial of first-line therapy in 861 patients.
Disclosures: Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
