Abstract P3-11-05: Three-year efficacy and safety of neoadjuvant chemotherapy with pertuzumab, atezolizumab, docetaxel, and trastuzumab in patients with stage II/III ERBB2-positive breast cancer (NeoPATH): a nonrandomized, multi-institutional, phase 2 trial

Abstract Background: In the primary analysis of the NeoPATH trial, neoadjuvant pertuzumab, atezolizumab, docetaxel, and trastuzumab (PATH) led to 61% of patients with stage II/III ERBB2-positive breast cancer having a pathological complete response (pCR; defined as no invasive cancer cells in the breast and regional lymph nodes [ypT0/isN0] and the absence of lymphovascular cancer invasion). Here, we report the analysis of secondary endpoints, including a 3-year event-free survival rate, overall survival, and long-term safety. Methods: In this nonrandomized, multi-institutional, single-arm phase 2 trial, patients with stage II/III ERBB2-positive breast cancer received up to six cycles of neoadjuvant PATH, followed by definitive surgery. Patients achieving pCR received 12 cycles of adjuvant atezolizumab, trastuzumab, and pertuzumab (AHP) every 3 weeks, while those without pCR received 14 cycles of atezolizumab plus trastuzumab emtansine (T-DM1) every 3 weeks. Results: Of the 67 enrolled patients, 65 (97%) completed six cycles of neoadjuvant therapy, and 41 (61%) achieved pCR, all completing 12 cycles of adjuvant AHP. Among the 26 patients without pCR (including one with disease progression that precluded surgery), 21 (81%) completed the 14 cycles of adjuvant atezolizumab plus T-DM1. The median follow-up was 39.4 months. The estimated 3-year event-free survival rate was 89% (95% confidence interval [CI], 81–98) in the intention-to-treat population, with rates of 97% and 75% for patients with and without pCR, respectively (hazard ratio [HR], 0.1; 95% CI, 0.01–0.83). Five events occurred: one local disease progression that precluded surgery, two distant breast cancer recurrences, and two second primary malignancies (thymic carcinoma and glioblastoma). Only two patients died; the estimated 3-year overall survival rate was 98% (95% CI, 96–100). Grade 3 or higher adverse events occurred in 29 patients (43%), primarily during the neoadjuvant phase, most commonly neutropenia (n=11) and febrile neutropenia (n=6). Grade 3 or higher immune-related adverse events (n=4) occurred exclusively during the neoadjuvant phase, and one patient died of sepsis during adjuvant treatment. Conclusion: In patients with stage II/III ERBB2-positive breast cancer, replacing carboplatin with atezolizumab in neoadjuvant therapy and adding atezolizumab to adjuvant therapy shows promising long-term efficacy and acceptable safety profile. Citation Format: Junghoon Shin, Hee Kyung Ahn, Sung Hoon Sim, Koung Jin Suh, Min Hwan Kim, Jae Ho Jeong, Ji-Yeon Kim, Dae-Won Lee, Jin-Hee Ahn, Heejung Chae, Kyung-Hun Lee, Jee Hyun Kim, Keun Seok Lee, Joo Hyuk Sohn, Yoon-La Choi, Seock-Ah Im, Kyung Hae Jung, Yeon Hee Park. Three-year efficacy and safety of neoadjuvant chemotherapy with pertuzumab, atezolizumab, docetaxel, and trastuzumab in patients with stage II/III ERBB2-positive breast cancer (NeoPATH): a nonrandomized, multi-institutional, phase 2 trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-11-05.