Abstract PS2-08-27: Final Analysis of a Prospective Observational Study to Evaluate the Impact of Comprehensive Genome Profiling on Treatment Decision Making in Metastatic or Recurrent Breast Cancer in Japan: JBCRG-C07 REIWA Study

Abstract Background: Comprehensive genome profiling (CGP) has been covered by insurance in Japan since June 2019. We conducted a prospective observational study (JBCRG-C07 (REIWA study), UMIN000038065) to determine the proportion of patients with stage IV or recurrent breast cancer (MBC) who received matched therapy (MT) identified by CGP since January 2020. Methods: A total of 602 patients with stage IV or recurrent MBC who consented to FoundationOne® CDx (F1CDx) or FoundationOne® Liquid CDx (F1LCDx) testing were prospectively enrolled. After excluding cases without valid testing or expert panel review, 576 patients comprised the per-protocol set (PPS). The primary endpoint was the rate of receiving MT, and the secondary endpoints included the clinical utility of panel testing, such as overall survival (OS). Results: Among the 576 patients in the PPS, 490 underwent F1CDx and 86 underwent F1LCDx. The median age was 56 years, and 25.7% of patients had de novo stage IV disease. The median number of pretreatment regimens before testing was five in the luminal subtype (n = 310), two in the triple-negative subtype (n = 173), and four in the HER2-positive subtype (n = 93). MT was recommended for 362 patients (62.8%) and administered to 93 patients (16.1%). Accordingly, the primary endpoint—the proportion of patients receiving MT among those for whom MT was recommended—was 25.7% (93/362). The most frequently administered MT within clinical trials was HER2 tyrosine kinase inhibitor therapy for ERBB2-mutated luminal breast cancer, whereas the most common off-trial MTs were immune checkpoint inhibitors (31.9%) primarily for TMB-high tumors and mTOR inhibitors (24.6%) primarily for tumors harboring PIK3CA mutations.During the follow-up period (median, 13.5 months), 412 deaths (71.5%) occurred. OS was significantly longer in the MT group than in the non-MT group (median 21.1 vs. 14.4 months; HR 0.651, 95% CI 0.494-0.857; P = 0.002).Subtype-specific analysis showed a significant OS benefit in the luminal subtype (22.3 vs. 15.1 months; HR 0.565, 95% CI 0.396-0.809; P = 0.002), whereas no significant benefit was observed in the triple-negative (14.0 vs. 11.8 months; HR 0.758, 95% CI 0.428-1.345; P = 0.342) or HER2-positive subtype (25.6 vs. 23.9 months; HR 1.057, 95% CI 0.530-2.107; P = 0.874). Conclusions: Among MBC patients recommended for targeted therapy through CGP, approximately one-quarter received MT and demonstrated an improved OS. An OS benefit was observed in the luminal subtype but not in the triple-negative or HER2-positive subtypes, highlighting the need for effective MT options and expanded early line clinical trials for these groups in Japan. Citation Format: H. Tada, H. Masuda, Y. Sagara, Y. Adachi, T. Iwatani, Y. Uemoto, O. Yoko, Y. Kajiwara, D. Kitagawa, T. Kogawa, T. Shien, Y. Tanabe, M. Tanioka, F. Hara, H. Yasojima, K. Yoshimura, H. Iwata, S. Saji, N. Masuda. Final Analysis of a Prospective Observational Study to Evaluate the Impact of Comprehensive Genome Profiling on Treatment Decision Making in Metastatic or Recurrent Breast Cancer in Japan: JBCRG-C07 REIWA Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-08-27.