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MADRID – Treatment with a new nucleoside-analogue drug produced clinically meaningful improvements in survival and performance status in a phase III trial that enrolled 800 patients with metastatic colorectal cancer who had failed at least two prior chemotherapy regimens.
In addition to a statistically significant, 32% cut in mortality during a median follow-up of 8 months, treatment with TAS-102 was “well tolerated,” and extended the time to deterioration of performance status by more than 40% compared with patients randomized to placebo, Dr. Erik Van Cutsem said at the European Society for Medical Oncology Congress.
S-102’s ability to stabilize patient performance status, along with its benefit for the study’s primary endpoint of overall survival, is “an important clinical parameter, a real benefit” that shows the drug’s positive effect on quality of life, said Dr. Cutsem, professor and head of clinical digestive oncology at the University Hospital, Leuven, Belgium.
TAS-102 contains trifluridine, a nucleoside analogue that gets incorporated into tumor cell DNA, causing dysfunction and inhibited tumor growth. A second agent in the TAS-120 formulation, tipiracil hydrochloride, inhibits trifluridine breakdown.
The RECOURSE (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) trial randomized 800 patients with metastatic colorectal cancer who had failed at least two prior regimens at 114 sites in 13 countries from June 2012 to October 2013. More than half the patients had failed or were intolerant of at least four prior regimens, and more than three-quarters of enrolled patients had been diagnosed with metastatic disease 18 months prior to study entry. Patients’ median age was 63 years, and at entry they all had an Eastern Cooperative Oncology Group performance status rating of 0 or 1.
Patients received 35 mg/m2 oral TAS-102 b.i.d. on days 1-5 and 8-12 for one cycle, repeated every 4 weeks, or placebo in addition to best supportive care. Treatment with the active agent produced a hazard ratio of 0.68 (confidence interval, 0.58-0.81; P < .0001), Dr. Van Cutsem reported. After 1 year, 27% of the 534 patients on TAS-102 treatment remained alive, compared with 18% of the 266 patients randomized to placebo. Prespecified subgroup analyses showed a consistent benefit across all subgroups.
A multivariate analysis showed a similar impact of treatment on overall survival. Secondary analysis showed that TAS-102 treatment was linked to a significant improvement in progression-free survival (HR, 0.48; CI, 0.41-0.57; P < .0001). The median time to deterioration to a performance status rating of 2 was 5.7 months among patients who received TAS-102 and 4.0 months among placebo patients.
TAS-102 produced a low level of nonhematologic grade 3 or 4 adverse events. The most common, usually grade 1 or 2, were nausea, fatigue, diarrhea, and vomiting. It did not produce any excess cardiac or thromboembolic events, and had no effect on liver function or creatinine levels. The novel agent produced a 38% incidence of grade 3 or 4 neutropenia, but grade 3 or 4 febrile neutropenia was limited to 4% of patients, Dr. Van Cutsem noted. Grade 3 anemia occurred in 18% of patients on the combination agent, and 5% had grade 3 or 4 thrombocytopenia.
RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi.
On Twitter @mitchelzoler
The results of RECOURSE were robust and convincing and clearly in favor of TAS-102. This will be a very important drug in the future.
The efficacy of TAS-102 looks similar to what was recently reported for regorafenib in similar patients with refractory, metastatic colorectal cancer (Lancet 2013;381:303-12), which now makes these two agents competitors in the same situation. But TAS-102 and regorafenib have substantially different safety profiles. TAS-102 treatment produced many episodes of grade 3 or 4 neutropenia, but a much smaller number of patients developed febrile neutropenia. This toxicity is manageable. TAS-102 does not cause the hand-foot syndrome that regorafenib often triggers.
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| Mitchel L. Zoler/Frontline Medical News Dr. Christophe Tournigand |
The efficacy of TAS-102 in the very advanced cases enrolled in the trial raises questions about how it will perform when used on less advanced patients, and whether it has a role as first- or second-line treatment. It will also be important to determine how well TAS-102 can be used in combination with other drugs; I suspect it may be easier to combine with other agents than regorafenib. TAS-102 has a mechanism of action very similar to that of fluorouracil, and it is intriguing to imagine that perhaps someday TAS-102 will replace fluorouracil as a mainstay of colorectal cancer treatment.
Dr. Christophe Tournigand is professor and head of medical oncology at Henri Mondor University Hospital in Créteil, France. He has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer. He made these comments as designated discussant for the RECOURSE trial and in an interview.
The results of RECOURSE were robust and convincing and clearly in favor of TAS-102. This will be a very important drug in the future.
The efficacy of TAS-102 looks similar to what was recently reported for regorafenib in similar patients with refractory, metastatic colorectal cancer (Lancet 2013;381:303-12), which now makes these two agents competitors in the same situation. But TAS-102 and regorafenib have substantially different safety profiles. TAS-102 treatment produced many episodes of grade 3 or 4 neutropenia, but a much smaller number of patients developed febrile neutropenia. This toxicity is manageable. TAS-102 does not cause the hand-foot syndrome that regorafenib often triggers.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Christophe Tournigand |
The efficacy of TAS-102 in the very advanced cases enrolled in the trial raises questions about how it will perform when used on less advanced patients, and whether it has a role as first- or second-line treatment. It will also be important to determine how well TAS-102 can be used in combination with other drugs; I suspect it may be easier to combine with other agents than regorafenib. TAS-102 has a mechanism of action very similar to that of fluorouracil, and it is intriguing to imagine that perhaps someday TAS-102 will replace fluorouracil as a mainstay of colorectal cancer treatment.
Dr. Christophe Tournigand is professor and head of medical oncology at Henri Mondor University Hospital in Créteil, France. He has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer. He made these comments as designated discussant for the RECOURSE trial and in an interview.
The results of RECOURSE were robust and convincing and clearly in favor of TAS-102. This will be a very important drug in the future.
The efficacy of TAS-102 looks similar to what was recently reported for regorafenib in similar patients with refractory, metastatic colorectal cancer (Lancet 2013;381:303-12), which now makes these two agents competitors in the same situation. But TAS-102 and regorafenib have substantially different safety profiles. TAS-102 treatment produced many episodes of grade 3 or 4 neutropenia, but a much smaller number of patients developed febrile neutropenia. This toxicity is manageable. TAS-102 does not cause the hand-foot syndrome that regorafenib often triggers.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Christophe Tournigand |
The efficacy of TAS-102 in the very advanced cases enrolled in the trial raises questions about how it will perform when used on less advanced patients, and whether it has a role as first- or second-line treatment. It will also be important to determine how well TAS-102 can be used in combination with other drugs; I suspect it may be easier to combine with other agents than regorafenib. TAS-102 has a mechanism of action very similar to that of fluorouracil, and it is intriguing to imagine that perhaps someday TAS-102 will replace fluorouracil as a mainstay of colorectal cancer treatment.
Dr. Christophe Tournigand is professor and head of medical oncology at Henri Mondor University Hospital in Créteil, France. He has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer. He made these comments as designated discussant for the RECOURSE trial and in an interview.
MADRID – Treatment with a new nucleoside-analogue drug produced clinically meaningful improvements in survival and performance status in a phase III trial that enrolled 800 patients with metastatic colorectal cancer who had failed at least two prior chemotherapy regimens.
In addition to a statistically significant, 32% cut in mortality during a median follow-up of 8 months, treatment with TAS-102 was “well tolerated,” and extended the time to deterioration of performance status by more than 40% compared with patients randomized to placebo, Dr. Erik Van Cutsem said at the European Society for Medical Oncology Congress.
S-102’s ability to stabilize patient performance status, along with its benefit for the study’s primary endpoint of overall survival, is “an important clinical parameter, a real benefit” that shows the drug’s positive effect on quality of life, said Dr. Cutsem, professor and head of clinical digestive oncology at the University Hospital, Leuven, Belgium.
TAS-102 contains trifluridine, a nucleoside analogue that gets incorporated into tumor cell DNA, causing dysfunction and inhibited tumor growth. A second agent in the TAS-120 formulation, tipiracil hydrochloride, inhibits trifluridine breakdown.
The RECOURSE (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) trial randomized 800 patients with metastatic colorectal cancer who had failed at least two prior regimens at 114 sites in 13 countries from June 2012 to October 2013. More than half the patients had failed or were intolerant of at least four prior regimens, and more than three-quarters of enrolled patients had been diagnosed with metastatic disease 18 months prior to study entry. Patients’ median age was 63 years, and at entry they all had an Eastern Cooperative Oncology Group performance status rating of 0 or 1.
Patients received 35 mg/m2 oral TAS-102 b.i.d. on days 1-5 and 8-12 for one cycle, repeated every 4 weeks, or placebo in addition to best supportive care. Treatment with the active agent produced a hazard ratio of 0.68 (confidence interval, 0.58-0.81; P < .0001), Dr. Van Cutsem reported. After 1 year, 27% of the 534 patients on TAS-102 treatment remained alive, compared with 18% of the 266 patients randomized to placebo. Prespecified subgroup analyses showed a consistent benefit across all subgroups.
A multivariate analysis showed a similar impact of treatment on overall survival. Secondary analysis showed that TAS-102 treatment was linked to a significant improvement in progression-free survival (HR, 0.48; CI, 0.41-0.57; P < .0001). The median time to deterioration to a performance status rating of 2 was 5.7 months among patients who received TAS-102 and 4.0 months among placebo patients.
TAS-102 produced a low level of nonhematologic grade 3 or 4 adverse events. The most common, usually grade 1 or 2, were nausea, fatigue, diarrhea, and vomiting. It did not produce any excess cardiac or thromboembolic events, and had no effect on liver function or creatinine levels. The novel agent produced a 38% incidence of grade 3 or 4 neutropenia, but grade 3 or 4 febrile neutropenia was limited to 4% of patients, Dr. Van Cutsem noted. Grade 3 anemia occurred in 18% of patients on the combination agent, and 5% had grade 3 or 4 thrombocytopenia.
RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi.
On Twitter @mitchelzoler
MADRID – Treatment with a new nucleoside-analogue drug produced clinically meaningful improvements in survival and performance status in a phase III trial that enrolled 800 patients with metastatic colorectal cancer who had failed at least two prior chemotherapy regimens.
In addition to a statistically significant, 32% cut in mortality during a median follow-up of 8 months, treatment with TAS-102 was “well tolerated,” and extended the time to deterioration of performance status by more than 40% compared with patients randomized to placebo, Dr. Erik Van Cutsem said at the European Society for Medical Oncology Congress.
S-102’s ability to stabilize patient performance status, along with its benefit for the study’s primary endpoint of overall survival, is “an important clinical parameter, a real benefit” that shows the drug’s positive effect on quality of life, said Dr. Cutsem, professor and head of clinical digestive oncology at the University Hospital, Leuven, Belgium.
TAS-102 contains trifluridine, a nucleoside analogue that gets incorporated into tumor cell DNA, causing dysfunction and inhibited tumor growth. A second agent in the TAS-120 formulation, tipiracil hydrochloride, inhibits trifluridine breakdown.
The RECOURSE (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) trial randomized 800 patients with metastatic colorectal cancer who had failed at least two prior regimens at 114 sites in 13 countries from June 2012 to October 2013. More than half the patients had failed or were intolerant of at least four prior regimens, and more than three-quarters of enrolled patients had been diagnosed with metastatic disease 18 months prior to study entry. Patients’ median age was 63 years, and at entry they all had an Eastern Cooperative Oncology Group performance status rating of 0 or 1.
Patients received 35 mg/m2 oral TAS-102 b.i.d. on days 1-5 and 8-12 for one cycle, repeated every 4 weeks, or placebo in addition to best supportive care. Treatment with the active agent produced a hazard ratio of 0.68 (confidence interval, 0.58-0.81; P < .0001), Dr. Van Cutsem reported. After 1 year, 27% of the 534 patients on TAS-102 treatment remained alive, compared with 18% of the 266 patients randomized to placebo. Prespecified subgroup analyses showed a consistent benefit across all subgroups.
A multivariate analysis showed a similar impact of treatment on overall survival. Secondary analysis showed that TAS-102 treatment was linked to a significant improvement in progression-free survival (HR, 0.48; CI, 0.41-0.57; P < .0001). The median time to deterioration to a performance status rating of 2 was 5.7 months among patients who received TAS-102 and 4.0 months among placebo patients.
TAS-102 produced a low level of nonhematologic grade 3 or 4 adverse events. The most common, usually grade 1 or 2, were nausea, fatigue, diarrhea, and vomiting. It did not produce any excess cardiac or thromboembolic events, and had no effect on liver function or creatinine levels. The novel agent produced a 38% incidence of grade 3 or 4 neutropenia, but grade 3 or 4 febrile neutropenia was limited to 4% of patients, Dr. Van Cutsem noted. Grade 3 anemia occurred in 18% of patients on the combination agent, and 5% had grade 3 or 4 thrombocytopenia.
RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi.
On Twitter @mitchelzoler
AT ESMO 2014
Key clinical point: TAS-102 treatment significantly boosted overall survival with good tolerability in patients with metastatic colorectal cancer refractory to at least two prior treatments in a phase III study.
Major finding: TAS-102 treatment improved overall survival by a hazard ratio of 0.68 compared with placebo.
Data source: RECOURSE, a randomized study with 800 patients at 114 centers in 13 countries.
Disclosures: RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi. Dr. Tournigand has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer.
