Debu Tripathy, MD: We don’t know the optimal timing to start neratinib. The study initially allowed up to 2 years. A very small number of patients were enrolled under those eligibility criteria, and then it was brought down to within 1 year. There was an exploratory analysis that was presented at the San Antonio meetings in 2017 that looked at the patients who got it within 6 months of completing trastuzumab, within 12 months, or within 2 years. There was a suggestion that the best outcomes were after using it within 6 months of completing trastuzumab. That’s my preference. That study obviously didn’t have the statistical power or design to really answer that definitively, but there’s a hint of that.

Patients who start within 6 months seem to have a better outcome in the analysis I mentioned from San Antonio. It didn’t really have rigorous statistical power, but these patients, the hormone receptor—positive subtype, derived a 5% benefit or so. That number seemed to be less, maybe around 3%, if you went out to a year and was almost negligible for the patients who were started between 1 and 2 years.

Ruta D. Rao, MD: The optimal timing for starting neratinib seems to be within 12 months of completing adjuvant trastuzumab, and this was based on the subgroup analysis from the ExteNET trial. In fact, the largest benefit was actually seen in the patients who started neratinib with 6 months of completing their adjuvant trastuzumab.

Patient subgroups were analyzed based on when they started neratinib after completing the adjuvant trastuzumab. For the patients who started within 6 months, the hazard ratio was 0.62. For the patients who started within 12 months, the hazard ratio was 0.70. For the patients who started at 12 months or later after the completion of their adjuvant trastuzumab, these patients did not seem to benefit, as the hazard ratio was 1.00. This was all based on subgroup analysis in the ExteNET trial.

Transcript Edited for Clarity