Abstract GS1-11: Sacituzumab Govitecan (SG) vs Treatment of Physician’s Choice (TPC): Efficacy by Trop-2 Expression in the TROPiCS-02 Study of Patients (Pts) With HR+/HER2– Metastatic Breast Cancer (mBC)

Abstract

Abstract Background: HR+/HER2– mBC, the most common subset of breast cancer, is treated with sequential endocrine therapy + targeted agents followed by sequential single-agent chemotherapy (CT), with increasingly shorter benefit duration with each subsequent treatment. High Trop-2 expression is observed in breast cancer regardless of subtype. SG is a Trop-2-directed antibody-drug conjugate approved for pre-treated metastatic triple-negative breast cancer. In the phase 3 TROPiCS-02 study, SG showed both significant progression-free survival (PFS) benefit (HR, 0.66; P<0.001; median 5.5 vs 4.0 mo; JCO 2022) at the primary analysis and overall survival (OS) benefit (median 14.4 vs 11.2 mo; HR, 0.79; P=0.02; ESMO 2022) at the 2nd planned interim OS analysis vs TPC in pretreated HR+/HER2- mBC. Here we compare efficacy outcomes for SG and TPC by Trop-2 expression. Methods: Eligible pts had HR+/HER2- locally recurrent inoperable or mBC; received ≥1 prior taxane, endocrine therapy, a CDK4/6 inhibitor; and received 2-4 prior CT regimens for mBC. Pts were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (eribulin, gemcitabine, capecitabine, or vinorelbine) until disease progression or unacceptable toxicity. The primary endpoint was PFS by independent review per RECIST v1.1; OS and objective response rate (ORR) were key secondary endpoints. ORR was assessed by blinded independent central review per RECIST v1.1. Membrane Trop-2 expression on archival tumor tissue was assessed by immunohistochemistry and expressed as a histochemical score (H-score; range, 0-300); efficacy outcomes were assessed in H-score <100 and ≥100 groups. The H-score <100 group was further divided into H-score ≤10 and >10- <100 subgroups to assess the activity of SG in pts with very low Trop-2 expression. Results: Data cut-off was January 3, 2022 for PFS (median follow-up, 10.2 mo) and July 1, 2022 for OS (median follow-up, 12.5 mo). In total, 543 pts were randomized to receive SG (n=272) vs TPC (n=271). Pts had a median of 3 prior CT regimens for mBC; 95% had visceral metastases. There were 238 (88%) vs 224 (83%) Trop-2-evaluable pts in the SG vs TPC groups, respectively; of these, 95% had tumors with Trop-2 H-score >0. Of Trop-2-evaluable pts, 192 (42%) and 270 (58%) had H-scores <100 and ≥100, respectively. Demographics and baseline characteristics were generally consistent across H-score groups. PFS and OS benefit was observed for SG vs TPC across both Trop-2 groups (Table). Median PFS was 5.3 vs 4.0 mo (HR, 0.77; 95% CI, 0.54-1.09) and 6.4 vs 4.1 mo (HR, 0.60; 95% CI, 0.44-0.81) in the H-score <100 and ≥100 groups; median OS was 14.6 vs 11.3 mo (HR, 0.75; 95% CI, 0.54-1.04) and 14.4 vs 11.2 mo (HR, 0.83; 95% CI, 0.62-1.11), respectively. Disease response was observed in the 34 pts with H-score ≤10 who received SG. In pts who received SG, those with H-score ≤10, >10- <100, and ≥100 had ORRs of 24%, 18%, and 23%, respectively. The safety profile for SG by Trop-2 H-score was consistent with previous reports. Conclusions: In this TROPiCS-02 post-hoc analysis, improved efficacy with SG vs TPC was observed regardless of Trop-2 expression, and there was no clear level of Trop-2 expression at which a better treatment effect for SG was observed. These results support SG as an effective novel treatment option for patients with pretreated, endocrine-resistant HR+/HER2- mBC, and reinforce that Trop-2 testing is not required for SG treatment. Table Citation Format: Hope Rugo, Aditya Bardia, Frederik Marmé, Javier Cortés, Peter Schmid, Delphine Loirat, Olivier Trédan, Eva Ciruelos, Florence Dalenc, Patricia Gómez Pardo, Komal Jhaveri, Monica Motwani, Oh Kyu Yoon, Hao Wang, Wendy Verret, Sara Tolaney. Sacituzumab Govitecan (SG) vs Treatment of Physician’s Choice (TPC): Efficacy by Trop-2 Expression in the TROPiCS-02 Study of Patients (Pts) With HR+/HER2– Metastatic Breast Cancer (mBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-11.