The most important new paradigm in the field of systemic breast cancer treatment is the concept of treatment intensifcation with trastuzumab emtansine in case of poor response to neoadjuvant chemotherapy in HER2+ disease. In the phase 3 KATHERINE study, 1,486 patients who did not achieve pathological complete response after standard neoadjuvant chemotherapy in combination with trastuzumab +/- pertuzumab were randomly assigned to 14 cycles of trastuzumab or 14 cycles of trastuzumab emtansine. The patients treated with the latter treatment had a 50% reduction in the risk of invasive breast cancer recurrence or death, with a probability of being free of invasive cancer at 3 years of 88.3% in the trastuzumab emtansine arm and 77.0% in the trastuzumab arm. Neoadjuvant treatment is now de facto the standard of care for HER2+ disease, except for patients who are candidates for the Tolaney regimen. In hormone receptor positive metastatic disease, further studies have positioned the CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib as the treatment of choice in first or second line. After PALOMA-3 showed a trend towards an improved OS of the same magnitude as the improvement shown for PFS, concerns about accelerated post-treatment progression are receding.
In the same disease setting, the SOLAR-1 study showed a PFS benefit of adding alpelisib (a PI3K inhibitor) to fulvestrant in patients with tumors harboring a PIK3CA mutation (median PFS of 11.0 vs 5.7 months). The identification of PIK3CA mutations on the tumor and/or cfDNA will soon become a standard in this context. Finally, the IMPASSION130 study, a phase 3 study in which 451 first line metastatic triple negative breast cancer patients were randomly assigned to nab-paclitaxel + atezolizumab or nab-paclitaxel + placebo, showed a modest PFS benefit in the ITT population, with a median PFS of 7.2 months in the immunotherapy arm and 5.5 months in the placebo arm. Although the statistical plan did not allow for the analysis of this endpoint, it was reported that in the subgroup of patients whose tumor was PD-L1 positive, the median OS in the atezolizumab arm reached 25.0 months, vs 15.5 months in the placebo arm (no p-value).
