389P Efficacy and safety analyses by prior lines of chemotherapy from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC)

SG is a Trop-2–directed antibody-drug conjugate approved for pretreated HR+/HER2- (IHC 0, 1+, or 2+/ISH-) mBC in the US. In the TROPiCS-02 study, SG treatment showed statistically significant improvement in progression-free survival (PFS; hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.53-0.83) and overall survival (OS; HR 0.79; 95% CI 0.65-0.96) vs TPC with manageable safety in pts with pretreated HR+/HER2- mBC (Rugo et al. ESMO 2022 ). Outcomes worsen with multiple prior lines of chemotherapy (LoT). We present a post-hoc analysis of outcomes with SG vs TPC by prior LoT from TROPiCS-02. Pts with HR+/HER2- mBC and ≥ 1 endocrine therapy, taxane, and CDK4/6 inhibitor, and 2 to 4 prior LoT for mBC, were randomized to SG (10 mg/kg IV Days 1 and 8, Q3W) or TPC. The primary endpoint was PFS; secondary endpoints included OS, objective response rate (ORR), clinical benefit rate (CBR), and safety. This analysis included pts with 2 vs ≥ 3 prior LoT in the metastatic setting. 543 pts were randomized to SG (n = 272; 113 (42%) had 2 prior LoT, 159 (58%) had ≥ 3) and TPC (n = 271; 120 (44%) had 2 prior LoT, 151 (56%) had ≥ 3). Baseline characteristics were similar in pts with 2 and ≥ 3 prior LoT and across treatments. Median PFS and OS were improved with SG vs TPC irrespective of prior LoT, with HR of 0.61 and 0.82 in pts with 2 prior LoT and 0.72 and 0.78 in pts with ≥ 3 prior LoT, respectively (Table). CBR was improved with SG vs TPC in pts with 2 and ≥ 3 prior LoT, ORR was improved in pts with 2 prior LoT, and the safety profile was similar in both subgroups (Table).Table: 389PEfficacy, ITT2 Prior LoT≥3 Prior LoTSG (n=113)TPC (n=113)SG (n=159)TPC (n=158)Median PFSa,b (95% CI), mo5.7 (4.2-8.5)4.1 (2.8-5.6)5.3 (4.0-6.9)4.0 (2.9-4.4)HR (95% CI)0.61 (0.44-0.84)0.72 (0.54-0.97)Median OSc (95% CI), mo15.3 (12.7-19.8)12.4 (10.4-14.9)13.9 (12.3-15.5)10.3 (8.7-12.4)HR (95% CI)0.82 (0.60-1.12)0.78 (0.61-1.01)ORRa,c(95% CI), %30 (22-39)16 (10-24)14 (9-21)13 (8-19)CBRa,c(95% CI), %41 (32-50)25 (17-34)29 (22-37)20 (14-27)Safety, all treated, n (%)SG (n=112)TPC (n=109)SG (n=156)TPC (n=140)Any grade TEAEsc112 (100)106 (97)156 (100)133 (95)Grade 3/479 (71)58 (53)113 (72)92 (66)aPer independent central review. bData cutoff: Jan 3, 2022; cJul 1, 2022. Open table in a new tab aPer independent central review. bData cutoff: Jan 3, 2022; cJul 1, 2022. Regardless of number of prior LoT, SG demonstrated improved efficacy vs TPC in pts with HR+/HER2- mBC, with manageable safety across subgroups. Findings are consistent with the ITT population, demonstrating the potential for pts to benefit from SG in earlier LoT. Table