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Neratinib plus paclitaxel was found not superior to trastuzumab plus paclitaxel as first-line therapy for ERBB2-positive metastatic breast cancer in an international phase II trial, according to investigators.
Recent research had suggested that small-molecule ERBB2 kinase inhibitors might be particularly effective against CNS metastases in such cases, so investigators performed the open-label randomized clinical trial in 479 women at 188 medical centers. After a median follow-up of 23 months, the primary endpoint – median progression-free survival – was 12.9 months for both neratinib-paclitaxel and trastuzumab-paclitaxel, said Dr. Ahmad Awada of the Medical Oncology Clinic, Jules Bordet Institute, Brussels, and his associates.
This outcome was consistent across all subgroups of patients, regardless of age, race, area of residence, hormone receptor status, or prior exposure to trastuzumab. Neratinib also was not superior to trastuzumab in any of the secondary study endpoints, including objective response rate, duration of response, and clinical benefit rate. These findings suggest that the two agents have similar efficacy in this patient population, the investigators said (JAMA Oncol. 2016 April 14. [doi: 10.1001/jamaoncol.2016.0237).
However, neratinib was associated with a reduced frequency of symptomatic or progressive CNS recurrences (RR, 0.48), as well as a delayed onset of such recurrences (HR, 0.45), compared with trastuzumab. This finding warrants further investigation in a larger trial with predefined CNS end points, they noted.
Neratinib was associated with more frequent adverse effects than trastuzumab, chiefly diarrhea (92.5% vs 33.3%) and nausea (44.2% vs 30.3%). Grade 3 diarrhea developed in 30.4% of patients receiving neratinib, compared with 3.8% of those receiving trastuzumab, and diarrhea accounted for discontinuation of study treatment in 3.8% of patients receiving neratinib, compared with 0.4% of those receiving trastuzumab. Aggressive primary prophylaxis of diarrhea should now be required for the first cycle of neratinib therapy, Dr. Awada and his associates added.
Neratinib’s benefits regarding CNS progression could prove to be an important therapeutic advance, given the debilitating sequelae of brain metastases and the especially poor prognosis associated with CNS progression.
However, the agent’s toxic effects are considerable. Grade 2-3 diarrhea, which developed in 65.4% of the neratinib arm of this study and 11.1% of the trastuzumab arm, should be considered clinically unacceptable.
Dr. Mark D. Pegram is at Stanford (Calif.) University’s Women’s Cancer Center. He reported serving as a consultant to Pfizer and Genentech/Roche, on the data and safety monitoring committee for a trial of neratinib monotherapy, and on the steering committee for a trial sponsored by Oncothyreon. Dr. Pegram made these remarks in an editorial accompanying Dr. Awada’s report (JAMA Oncol. 2016 April 14. doi: 10.1001/jamaoncol.2016.0238).
Neratinib’s benefits regarding CNS progression could prove to be an important therapeutic advance, given the debilitating sequelae of brain metastases and the especially poor prognosis associated with CNS progression.
However, the agent’s toxic effects are considerable. Grade 2-3 diarrhea, which developed in 65.4% of the neratinib arm of this study and 11.1% of the trastuzumab arm, should be considered clinically unacceptable.
Dr. Mark D. Pegram is at Stanford (Calif.) University’s Women’s Cancer Center. He reported serving as a consultant to Pfizer and Genentech/Roche, on the data and safety monitoring committee for a trial of neratinib monotherapy, and on the steering committee for a trial sponsored by Oncothyreon. Dr. Pegram made these remarks in an editorial accompanying Dr. Awada’s report (JAMA Oncol. 2016 April 14. doi: 10.1001/jamaoncol.2016.0238).
Neratinib’s benefits regarding CNS progression could prove to be an important therapeutic advance, given the debilitating sequelae of brain metastases and the especially poor prognosis associated with CNS progression.
However, the agent’s toxic effects are considerable. Grade 2-3 diarrhea, which developed in 65.4% of the neratinib arm of this study and 11.1% of the trastuzumab arm, should be considered clinically unacceptable.
Dr. Mark D. Pegram is at Stanford (Calif.) University’s Women’s Cancer Center. He reported serving as a consultant to Pfizer and Genentech/Roche, on the data and safety monitoring committee for a trial of neratinib monotherapy, and on the steering committee for a trial sponsored by Oncothyreon. Dr. Pegram made these remarks in an editorial accompanying Dr. Awada’s report (JAMA Oncol. 2016 April 14. doi: 10.1001/jamaoncol.2016.0238).
Neratinib plus paclitaxel was found not superior to trastuzumab plus paclitaxel as first-line therapy for ERBB2-positive metastatic breast cancer in an international phase II trial, according to investigators.
Recent research had suggested that small-molecule ERBB2 kinase inhibitors might be particularly effective against CNS metastases in such cases, so investigators performed the open-label randomized clinical trial in 479 women at 188 medical centers. After a median follow-up of 23 months, the primary endpoint – median progression-free survival – was 12.9 months for both neratinib-paclitaxel and trastuzumab-paclitaxel, said Dr. Ahmad Awada of the Medical Oncology Clinic, Jules Bordet Institute, Brussels, and his associates.
This outcome was consistent across all subgroups of patients, regardless of age, race, area of residence, hormone receptor status, or prior exposure to trastuzumab. Neratinib also was not superior to trastuzumab in any of the secondary study endpoints, including objective response rate, duration of response, and clinical benefit rate. These findings suggest that the two agents have similar efficacy in this patient population, the investigators said (JAMA Oncol. 2016 April 14. [doi: 10.1001/jamaoncol.2016.0237).
However, neratinib was associated with a reduced frequency of symptomatic or progressive CNS recurrences (RR, 0.48), as well as a delayed onset of such recurrences (HR, 0.45), compared with trastuzumab. This finding warrants further investigation in a larger trial with predefined CNS end points, they noted.
Neratinib was associated with more frequent adverse effects than trastuzumab, chiefly diarrhea (92.5% vs 33.3%) and nausea (44.2% vs 30.3%). Grade 3 diarrhea developed in 30.4% of patients receiving neratinib, compared with 3.8% of those receiving trastuzumab, and diarrhea accounted for discontinuation of study treatment in 3.8% of patients receiving neratinib, compared with 0.4% of those receiving trastuzumab. Aggressive primary prophylaxis of diarrhea should now be required for the first cycle of neratinib therapy, Dr. Awada and his associates added.
Neratinib plus paclitaxel was found not superior to trastuzumab plus paclitaxel as first-line therapy for ERBB2-positive metastatic breast cancer in an international phase II trial, according to investigators.
Recent research had suggested that small-molecule ERBB2 kinase inhibitors might be particularly effective against CNS metastases in such cases, so investigators performed the open-label randomized clinical trial in 479 women at 188 medical centers. After a median follow-up of 23 months, the primary endpoint – median progression-free survival – was 12.9 months for both neratinib-paclitaxel and trastuzumab-paclitaxel, said Dr. Ahmad Awada of the Medical Oncology Clinic, Jules Bordet Institute, Brussels, and his associates.
This outcome was consistent across all subgroups of patients, regardless of age, race, area of residence, hormone receptor status, or prior exposure to trastuzumab. Neratinib also was not superior to trastuzumab in any of the secondary study endpoints, including objective response rate, duration of response, and clinical benefit rate. These findings suggest that the two agents have similar efficacy in this patient population, the investigators said (JAMA Oncol. 2016 April 14. [doi: 10.1001/jamaoncol.2016.0237).
However, neratinib was associated with a reduced frequency of symptomatic or progressive CNS recurrences (RR, 0.48), as well as a delayed onset of such recurrences (HR, 0.45), compared with trastuzumab. This finding warrants further investigation in a larger trial with predefined CNS end points, they noted.
Neratinib was associated with more frequent adverse effects than trastuzumab, chiefly diarrhea (92.5% vs 33.3%) and nausea (44.2% vs 30.3%). Grade 3 diarrhea developed in 30.4% of patients receiving neratinib, compared with 3.8% of those receiving trastuzumab, and diarrhea accounted for discontinuation of study treatment in 3.8% of patients receiving neratinib, compared with 0.4% of those receiving trastuzumab. Aggressive primary prophylaxis of diarrhea should now be required for the first cycle of neratinib therapy, Dr. Awada and his associates added.
FROM JAMA ONCOLOGY
Key clinical point: Neratinib plus paclitaxel was found not superior to trastuzumab plus paclitaxel for ERBB2-positive metastatic breast cancer.
Major finding: Median progression-free survival was 12.9 months for both neratinib-paclitaxel and trastuzumab-paclitaxel.
Data source: An international randomized controlled open-label phase II trial involving 479 patients followed for 2 years.
Disclosures: This trial was sponsored by Wyeth, Pfizer, and Puma Biotechnology, which were involved in the design and conduct of the study; the collection, analysis, and interpretation of the data; and the preparation of the report. Dr. Awada reported receiving an honorarium from Wyeth; his associates reported ties to numerous industry sources.