Curie Brief
Turn on cookies to sign in
Signing in saves your progress to your Curie account. We can only do that with cookies on — turn them on to continue.
News
A large phase III trial (EVOKE-03) found that adding the antibody-drug conjugate sacituzumab govitecan to pembrolizumab did not significantly improve survival in metastatic non-small cell lung cancer. Despite a 4-month PFS improvement, the result missed its statistical threshold, and overall survival trended slightly in favor of the control arm. Experts say pembrolizumab monotherapy remains the standard of care for PD-L1-high patients.
The EVOKE-03 trial set out to answer whether adding the antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy) to pembrolizumab (Keytruda) could improve outcomes for patients with metastatic non-small cell lung cancer (NSCLC) and high PD-L1 expression. The answer, presented at the World Conference on Lung Cancer in Seoul, was not encouraging — at least for now.
While median progression-free survival (PFS) improved from 7.7 to 11.8 months with the combination, the difference fell short of the prespecified statistical bar (p=0.0250 vs. required p=0.007). An interim overall survival (OS) analysis slightly favored the control arm (22.8 vs. 21.5 months), making a future OS benefit highly unlikely. Adverse events — including serious and fatal ones — were more common in the sacituzumab group.
Discussants noted that the phase II EVOKE-02 trial's promising 66.7% response rate came from just 30 patients, setting up an overestimation that the larger trial couldn't replicate. The combination's effect appeared more chemotherapy-like than transformative, converting some non-responders into short-term responders without extending the survival tail.
Key Takeaways:
Why it matters: With more than half of metastatic NSCLC patients failing initial pembrolizumab therapy, the field urgently needs better first-line options. EVOKE-03 is a reminder that promising phase II signals don't always translate — and that raising the bar for trial design is essential before adding toxicity to an already-effective regimen.
