In the Phase III ASCENT-04/KEYNOTE-D19 study in 443 patients with newly diagnosed, PD-L1–positive, inoperable locally advanced or metastatic triple-negative breast cancer, Trodelvy plus Keytruda improved PFS2 versus Keytruda plus chemotherapy, with median time to second subsequent therapy not yet reached vs. 21 months and a hazard ratio of 0.67. The ASCO 2025 update adds to prior results showing first-line PFS of 11.2 months vs. 7.8 months, a 35% reduction in risk of progression or death.

Why It Matters To Oncology

• PFS2 is an exploratory but clinically relevant readout in metastatic TNBC, especially when overall survival is immature and crossover can blur longer-term benefit.

• Here, the regimen showed durable benefit beyond first progression despite substantial crossover: 81% of control-arm patients who received second-line therapy went on to Trodelvy monotherapy.

• If regulators are persuaded, Trodelvy plus Keytruda could strengthen its case to become a new first-line option for PD-L1–positive advanced TNBC.

The Financials

• Gilead is awaiting an FDA decision on Trodelvy in certain first-line TNBC patients, a potential label expansion beyond its current later-line metastatic TNBC and pre-treated HR-positive/HER2-negative metastatic breast cancer uses.

• A first-line approval could materially expand Trodelvy’s addressable market and reinforce the strategic value of ADC-immunotherapy combinations in breast cancer.

• Merck also has a stake via Keytruda, already a backbone therapy in PD-L1–positive TNBC.

What They're Saying

• Investigator Kevin Kalinsky said the findings “demonstrate an improved clinical benefit” for patients assigned to front-line Trodelvy plus Keytruda, with a 33% reduction in risk of a PFS2 event.

• Kalinsky also noted regulatory tension: FDA has recently questioned PFS2 as a regulatory endpoint, while European regulators have been more willing to use it as supportive evidence.

• ASCO expert Eleonora Teplinsky said the analysis “really supports the long-term clinical benefit” and could help establish a new standard of care for PD-L1–positive untreated advanced TNBC.

What's Next

• The immediate watchpoint is the FDA’s review of Trodelvy in first-line TNBC and whether the agency gives any weight to the PFS2 dataset.

• Clinicians will also want longer follow-up for overall survival and additional detail on how post-progression therapies affected outcomes.

• More broadly, the case may influence how sponsors position PFS2 in oncology filings when crossover is common and survival readouts remain immature.