Abstract PD3-06: Association of intrinsic subtypes with pathological complete response (pCR) in the KRISTINE neoadjuvant phase 3 clinical trial in HER2-positive early breast cancer (EBC)

Introduction: Previous studies have shown that HER2+ breast cancer is biologically heterogenous and intrinsic subtypes can be identified (luminal A, luminal B, HER2-enriched [HER2-E] and basal-like). HER2-E predominates and is associated with higher response rates following anti-HER2-based chemotherapy or dual HER2 blockade (only with lapatinib and trastuzumab). We explored the ability of intrinsic subtypes to predict pCR in pts treated with anti-HER2 neoadjuvant therapy. Methods: KRISTINE (NCT02131064) is an open-label, phase 3 study of neoadjuvant trastuzumab emtansine + pertuzumab (T-DM1+P) vs docetaxel + carboplatin + trastuzumab + pertuzumab (TCH+P) in pts with HER2+ EBC. Treatment-naive pts with stage II–IIIC HER2+ EBC were randomized to receive 6 cycles of T-DM1+P or TCH+P and assessed for the primary endpoint, pCR (ypT0/is, ypN0). HER2 and hormone receptor (HR) status were centrally assessed. Gene expression (RNA) was assessed by a custom 800-gene codeset on the nCounter platform. Intrinsic subtypes were assessed with the research-based PAM50 classifier. Results: KRISTINE randomized 444 pts (data cutoff, Dec 3, 2015; TCH+P, n=221; T-DM1+P, n=223). PAM50 results were available for 354 pts (79.7% of the intent-to-treat [ITT] population). Baseline characteristics and efficacy in the PAM50 population were similar to that of the ITT population. The HER2-E subtype represented 54.8% of the samples (Table 1). Differences were observed by HR status. Almost all luminal tumors (131/132) were identified within HR+ disease. Of HR+ tumors, 32% were identified as HER2-E. In the TCH+P arm, the pCR rate was 72.1% for HER2-E vs 32.8% in the other subtypes combined (Table 2.) In the T-DM1+P arm, the pCR rate was 62.2% for HER2-E vs 26.9% in the other subtypes combined. No major differences were observed in pCR rates within the HER2-E subtype according to HR status. Further multivariable analyses assessing differences between treatment arms and treatment benefit across subtypes is ongoing. Conclusions: In this analysis from the KRISTINE study, HER2-E was the most common intrinsic subtype and was associated with the highest pCR rate with both regimens. Results are consistent with previous findings. The luminal A and B subtypes were well associated with HR+ status. A sizeable subgroup of the HER2-E subtype was HR+ (32%), and pCR rates within the HER2-E subtype seemed independent of HR status. Citation Format: Prat A, Slamon D, Hurvitz SA, Press MF, Lewis Phillips G, Lopez Valverde V, Kiermaier A, Helms H-J, Martin M, de Haas SL. Association of intrinsic subtypes with pathological complete response (pCR) in the KRISTINE neoadjuvant phase 3 clinical trial in HER2-positive early breast cancer (EBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD3-06.