SG plus pembrolizumab improved PFS2 versus chemotherapy plus pembrolizumab, despite high crossover to SG in the control arm.
touchONCOLOGY coverage of ASCO 2026
New data from ASCENT-04, presented during a late-breaking abstract session at ASCO 2026, evaluated progression-free survival after next line of treatment (PFS2) and subsequent therapies in patients with previously untreated PD-L1-positive metastatic triple-negative breast cancer (mTNBC).
The analysis builds on the primary ASCENT-04 results (NCT05382286), in which first-line sacituzumab govitecan (SG) plus pembrolizumab significantly improved progression-free survival (PFS) versus chemotherapy plus pembrolizumab.¹ At the time of the initial analysis, overall survival (OS) data were promising but immature. In this context, PFS2 may provide an additional measure of longer-term clinical benefit, particularly in ASCENT-04, where subsequent therapy or crossover may influence the interpretation of OS.
What did the data show?
In ASCENT-04, 443 patients with previously untreated PD-L1-positive mTNBC were randomized 1:1 to sacituzumab govitecan (SG) plus pembrolizumab or chemotherapy plus pembrolizumab.
PFS2 was defined as the time from randomization to first documented disease progression on next-line therapy, or death from any cause. Eligible patients in the chemotherapy plus pembrolizumab arm could receive SG after confirmed disease progression, either through on-study crossover or in a subsequent line.
At a median follow-up of 14.0 months for OS, 95 patients (43%) remained on study treatment in the SG plus pembrolizumab group and 52 patients (23%) remained on treatment in the chemotherapy plus pembrolizumab group.
Among patients who discontinued treatment, 69 of 125 in the SG plus pembrolizumab group received subsequent therapy. The most frequent subsequent therapies were taxanes (42%), platinum chemotherapy (33%), and capecitabine (33%). In the chemotherapy plus pembrolizumab group, 119 of 170 patients who discontinued treatment received subsequent therapy, most commonly SG (81%), followed by taxanes (9%) and capecitabine (9%).
PFS2 favored SG plus pembrolizumab despite crossover to SG in the chemotherapy plus pembrolizumab arm. PFS2 events occurred in 55 of 221 patients (25%) receiving SG plus pembrolizumab and 83 of 222 patients (37%) receiving chemotherapy plus pembrolizumab. Median PFS2 was not reached with SG plus pembrolizumab and was 21.0 months with chemotherapy plus pembrolizumab (stratified HR 0.67; 95% CI 0.48–0.95).
PFS2 rates were also higher with SG plus pembrolizumab at later time points. At 12 months, PFS2 rates were 80.0% versus 75.7%, respectively. At 18 months, rates were 71.9% versus 53.0%, and at 24 months, 63.7% versus 45.6%.
Median time to first subsequent therapy was longer with SG plus pembrolizumab than with chemotherapy plus pembrolizumab, at 17.3 months versus 9.8 months (stratified HR 0.59; 95% CI 0.46-0.76). Median time to second subsequent therapy was not reached with SG plus pembrolizumab and was 21.0 months with chemotherapy plus pembrolizumab (stratified HR 0.82; 95% CI 0.59-1.14).
Key clinical takeaway
In this exploratory post-hoc analysis of ASCENT-04, SG plus pembrolizumab improved PFS2 versus chemotherapy plus pembrolizumab in patients with previously untreated PD-L1-positive mTNBC suggesting a sustained long-term benefit beyond first progression.
Reporting the results at the meeting, study investigator Dr Kevin Kalinsky, Winship Cancer Institute of Emory University, Atlanta, GA, USA, added: “Despite the high rate of crossover from the control arm to monotherapy SG, time to first and second subsequent therapies demonstrate that participants receiving front-line SG and pembrolizumab experienced a longer initial disease control and delayed need for the initiation of subsequent therapy.” He concluded: “These results from ASCENT-04 further support the combination of front-line SG and pembrolizumab use for patients with PD-L1-positive advanced triple-negative breast cancer.”
References
- Tolaney SM, de Azambuja E, Kalinsky K, et al. ASCENT-04/KEYNOTE-D19 Clinical Trial Investigators. Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer. N Engl J Med. 2026 Jan 22;394(4):354-366.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (ChatGPT 5.5 [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: ASCENT-04: Further data supports front-line sacituzumab govitecan for PD-L1-positive advanced triple-negative breast cancer. touchONCOLOGY. 16th June 2026.
Editor: Gina Furnival
