Progression-free survival after next line of treatment (PFS2) and subsequent therapies (subs tx) in the ASCENT-03 study of participants (pts) with previously untreated metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) vs chemotherapy (chemo).

Abstract

1001 Background: In ASCENT-03, first-line (1L) SG led to a clinically meaningful improvement in PFS vs chemo (median, 9.7 vs 6.9 months [mo]; hazard ratio [HR], 0.62; 95% CI, 0.50-0.77; P < .0001) in previously untreated pts with mTNBC who were not candidates for PD-(L)1 inhibitors. Since overall survival data are immature, PFS2 can be used to assess long-term benefit as it accounts for the impact of initial and subs tx, including trial crossovers. We report PFS2 and subs tx from ASCENT-03. Methods: Pts (N = 558) were randomized 1:1 to SG (10 mg/kg IV, days 1 & 8 in 21-day cycles) or chemo (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin); primary end point was PFS by blinded independent central review (BICR). Eligible pts in the chemo group could receive 2L SG provided on study via crossover following BICR-verified progressive disease or in any subs line commercially; other subs txs per local practice were also permitted. PFS2 was defined as the time from randomization to the first documented progression on next-line therapy per investigator assessment or death due to any cause, whichever occurred first. Results: Median follow-up for OS was 13.2 mo; 75 (27%) pts remained on study treatment in the SG group (n = 279) and 39 (14%) in the chemo group (n = 279). Of the 204 pts in the SG group who discontinued tx, 126 received any subs tx, the most frequent of which were platinum chemo (40%), taxanes (29%), and gemcitabine (19%). Of 240 pts in the chemo group who discontinued tx, 179 received any subs tx, the most frequent of which were SG (82%), capecitabine (16%), platinum chemo (9%), and trastuzumab deruxtecan (9%). Median (95% CI) PFS2 was 18.2 mo (15.9-not reached [NR]) in the SG group and 14.0 mo (12.5-17.4) in the chemo group (stratified HR, 0.70; 95% CI, 0.55-0.90). PFS2 rates are in the Table. Median (95% CI) time to first subs tx was 11.2 mo (10.0-13.0) and 7.9 mo (7.2-9.0) for SG and chemo, respectively; median (95% CI) time to second subs tx was 17.3 mo (15.2- NR) and 16.6 mo (13.6-18.5). Conclusions: PFS2 was improved in the SG group compared with the chemo group despite crossover tx, with most pts who initiated subs tx in the chemo group receiving SG. The benefit of first-line SG is clinically relevant and sustained until the next line of therapy, which further supports SG as a potential new standard of care in pts with previously untreated mTNBC who are not candidates for PD-(L)1 inhibitors. Clinical trial information: NCT05382299 . SG Chemo Pts with PFS2 events, n/N (%) 114/279 (41) 143/279 (51) Median PFS2 (95% CI), mo 18.2 (15.9-NR) 14.0 (12.5-17.4) Stratified HR a (95% CI) 0.70 (0.55-0.90) Stratified log-rank nominal P -value a .0051 PFS2 rate (95% CI), % 12 mo 71 (65-76) 59 (53-65) 18 mo 52 (45-59) 41 (33-48) a SG vs chemo.