SABCS 2016. P4-22-13. Everolimus plus trastuzumab and paclitaxel as first-line therapy in women with HER2+ advanced breast cancer: Overall survival results from BOLERO-1

Yardley D, Hurvitz S, Jiang Z-f, Toi M, Burris H, Buyse M, Slamon D, Makhson A, Elsaid A, Lerzo G, Hellerstedt B, Nuzzo F, Sohn J, Manzyuk L, Cabaribere D, Lincy J, Weimann A, Noel-Baron F, Pacaud L, Andre F
Results: At data cutoff (Dec 31, 2015), the median duration of exposure was 40.8 weeks (range: 0.6-320.4) in the EVE arm and 48.1 weeks (range: 1.1-308.0) in the PBO arm. After a median follow-up of 60.3 mo, 350 deaths were recorded in the full population, 238 (49.6%) in the EVE arm and 112 (46.9%) pts in the PBO arm. In the full population, the median OS was comparable in the EVE vs PBO arms (48.6 mo vs 50.0 mo respectively; HR = 1.13; 95% CI: 0.90-1.42). In the HR- subpopulation, 138 deaths were recorded; 88 (42.3%) pts in the EVE arm and 50 (48.5%) pts in the PBO arm. In the HR- subpopulation, the median OS in the EVE arm was longer compared to PBO arm (57.0 mo vs 41.6 mo respectively; HR = 0.83; 95% CI: 0.59-1.18). Stomatitis, diarrhea, alopecia, cough, rash, pyrexia, neutropenia, and fatigue were the most frequent adverse events (AEs) reported in EVE arm (≥35%). AEs leading to dose interruption and/or change were reported in 441 (93.4%) pts in EVE arm and 165 (69.3%) pts in the PBO arm respectively. Overall, AEs leading to treatment discontinuation were reported in 262 (55.5%) pts in EVE arm and 98 (41.2%) pts in PBO arm. Serious AEs were reported in 171 (36.2%) pts in the EVE arm and 40 (16.8%) pts in the PBO arm respectively. On treatment AE related deaths were reported for 3.6% pts in the EVE arm and 0% pts in the PBO arm.

Conclusions: The median OS was similar in the EVE vs PBO arms for overall population. However, a prolongation of 15.4 mo in median OS of HR- subpopulation was observed in the EVE arm vs PBO arm in this exploratory analysis. Pts in the EVE arm had a manageable safety, consistent with the safety profile of EVE and no new safety signals were identified.

 CARE™ Faculty Perspective: The addition of everolimus, a mTOR inhibitor, to paclitaxel and trastuzumab did not significantly improve PFS in women with metastatic HER-2 + breast cancer (BOLERO-1: 15.0 vs 14.5 months). Overall survival was an exploratory endpoint for this study. At a median follow-up of 60 months, there was no statistically significant difference in median OS (48.6 vs 50 months; HR = 1.13) although women with HR – metastatic breast cancer appeared to benefit from the addition of everolimus (median OS 57 vs 41.6 months; NS) to paclitaxel/trastuzumab. More toxicity (e.g.  stomatitis, diarrhea, rash) was reported in the combination arm. These results do not support the addition of everolimus to standard therapy in this patient population. Prospective studies are needed to explore any potential benefit from the addition of everolimus to standard therapy in women with HER2 +, HR- disease.

Related Abstract of Interest:

SABCS 2016. P6-16-03. Phase 2 trial of everolimus and/or trastuzumab in hormone refractory, hormone receptor (HR)-positive, HER2-normal metastatic breast cancer (MBC)
Paplomata E et al.