Abstract PD3-11: A randomized, open-label, phase III trial of pertuzumab re-treatment in HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab, and chemotherapy: The Japan Breast Cancer Research Group-M05 (PRECIOUS) study

Background: Patients (pts) with HER2-positive locallyadvanced/metastatic breast cancer (LA/MBC) previously treated with pertuzumab(P)-containing regimens have few therapeutic options. The efficacy of Pre-treatment combined with trastuzumab (T)+chemotherapy as 3 or 4 -line chemotherapy was examined in such pts. Methods: Pts previously treated with P-containing regimens as1st/2nd-line treatment for LA/MBC were randomly assigned 1:1 to two groups(P+T+chemotherapy based on physicians’ choice (C) (PTC), and T+C (TC)),stratified by estrogen receptor status, previous P treatment duration, numberof previous chemotherapy regimens, and presence or absence of visceralmetastasis. The primary endpoint was investigator-assessed progression-freesurvival (PFS). Superiority of PTC to TC will be tested using a stratifiedlog-rank test that accounts for all stratification factors, and a one-sidedP-value of less than 0.05 will be considered an indicator of superiority. Thedistribution of PFS will be estimated using the Kaplan-Meier method. In addition,the hazard ratio and one-sided 95% CI of the therapeutic effect between thegroups will be calculated using the Cox proportional hazard model. Secondaryendpoints included independent reviewer assessed PFS, PFS in pts treated withT-DM1 as the latest regimen (PFS after T-DM1), objective response rate (ORR),overall survival (OS), safety, and health-related quality of life (HR-QoL). Results: Of the 219 pts enrolled, 217 (108 PTC, 109 TC) wereincluded in the intent-to-treat analysis. At the data cutoff (July 31, 2019),PFS and OS events were 184 (84.8%) and 84 (38.7%), respectively. Medianfollow-up time was 14.2 months (mo). Investigator-assessed PFS wassignificantly better in the PTC group (median PFS 5.3 vs. 4.2 mo; HR = 0.755[One-sided 95%CI upper limit, 0.967]; One-sided stratified log-rank test p =0.0217). Median PFS after T-DM1 (5.3 vs. 4.2 mo; HR = 0.801 [One-sided 95%CIupper limit, 1.061]; One-sided log-rank test p = 0.0952) and OS (28.8 vs. 23.4mo; HR = 0.713, [One-sided 95%CI upper limit, 1.026], One-sided log-rank test p= 0.062) tended to be longer in the PTC group, though further follow-up isneeded. The ORR with measurable disease (PTC (n = 90) 18.9% vs. TC (n = 92)19.6%) did not differ between the groups. The serious adverse event rate didnot differ between the groups (17.9% vs. 21.3%). There were no new safetysignals included cardiac events in the groups. In the comparison of HR-QoL bytime to deterioration analysis, there was no significant difference between thegroups in FACT-B trial outcome index (PTC 2.8 mo vs. TC 4.3 mo; HR = 1.274,log-rank test p = 0.2289).Conclusions: P re-treatment as 3 or 4 -line chemotherapy wasactive and feasible. P re-treatment can be a standard treatment option forpatients with HER2-positive LA/MBC previously treated with P.(ClinicalTrials.gov number: NCT02514681) Citation Format: Yutaka Yamamoto, Hiroji Iwata, Taira Naruto, Norikazu Masuda, Masato Takahashi, Tetsuhiro Yoshinami, Takayuki Ueno, Tatsuya Toyama, Takashi Yamanaka, Toshimi Takano, Masahiro Kashiwaba, Koichiro Tsugawa, Yoshie Hasegawa, Kenji Tamura, Hiroshi Tada, Fumikata Hara, Shigehira Saji, Satoshi Morita, Masakazu Toi, Shinji Ohno, Japan Breast Cancer Research Group. A randomized, open-label, phase III trial of pertuzumab re-treatment in HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab, and chemotherapy: The Japan Breast Cancer Research Group-M05 (PRECIOUS) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-11.