Progression-free survival after next line of treatment (PFS2) and subsequent therapies (subs tx) in the ASCENT-04 study of participants (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) plus pembrolizumab (pembro) vs chemotherapy (chemo) plus pembro.

Abstract

LBA1000 Background: In ASCENT-04, first-line (1L) SG + pembro led to a statistically significant and clinically meaningful improvement in PFS vs chemo + pembro (median, 11.2 vs 7.8 mo; hazard ratio [HR], 0.65; 95% CI, 0.51-0.84; P < .001) in pts with previously untreated PD-L1+ mTNBC. Overall survival (OS) data are immature. PFS2 is more strongly associated with OS than PFS and can be used to measure long-term clinical benefit in the absence of mature OS data or when OS may be impacted by crossover. We report PFS2 and subs tx from ASCENT-04. Methods: Pts (N = 443) were randomized 1:1 to SG (10 mg/kg IV, days 1 & 8) + pembro (200 mg, day 1, max 35 cycles) in 21-day cycles or chemo (gemcitabine + carboplatin, paclitaxel, or nab-paclitaxel) + pembro; the primary end point was PFS by blinded independent central review (BICR). Eligible pts in the chemo + pembro group could receive 2L SG provided on study via crossover following BICR-verified progressive disease (PD) or in any subs line commercially; other subs txs per local practice were also permitted. PFS2 was defined as the time from randomization to first documented PD on next-line therapy per investigator assessment or death due to any cause, whichever occurred first. Results: Median follow-up for OS was 14.0 mo; 95 (43%) pts remained on study tx in the SG + pembro group (n = 221) and 52 (23%) in the chemo + pembro group (n = 222). Of the 125 pts in the SG + pembro group who discontinued tx, 69 received any subs tx, the most frequent of which were taxanes (42%), platinum chemo (33%), and capecitabine (33%). Of the 170 pts in the chemo + pembro group who discontinued tx, 119 received any subs tx, the most frequent of which were SG (81%), taxanes (9%), and capecitabine (9%). Median PFS2 and PFS2 rates are in the Table. Median (95% CI) time to first subs tx was 17.3 mo (12.7-not reached [NR]) for SG + pembro and 9.8 mo (8.7-10.9) for chemo + pembro; median (95% CI) time to second subs tx was NR (22.9 mo-NR) and 21.0 mo (16.6-NR). Conclusions: PFS2 was improved in the SG + pembro group vs chemo + pembro group despite crossover tx, with most pts who initiated subs tx in the chemo + pembro group receiving SG. In pts with previously untreated PD-L1+ mTNBC, SG + pembro provided clinically relevant continued benefit beyond first progression, further supporting SG + pembro as a potential new standard of care. Clinical trial information: NCT05382286 . SG + pembro Chemo + pembro Pts with PFS2 events, n/N (%) 55/221 (25) 83/222 (37) Median PFS2 (95% CI), mo NR (NR-NR) 21.0 (16.0-NR) Stratified HR a (95% CI) 0.67 (0.48-0.95) Stratified log-rank nominal P -value a .0224 PFS2 rate (95% CI), % 12 mo 80.0 (73.8-84.9) 75.7 (69.1-81.1) 18 mo 71.9 (64.5-78.0) 53.0 (44.5-60.8) 24 mo 63.7 (51.1-73.9) 45.6 (35.6-55.1) a SG + pembro vs chemo + pembro.