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.