For metastatic NSCLC patients without actionable mutations, oncology experts say PD-L1 expression level, tumor histology, and side effect profiles — not just efficacy — should drive immune checkpoint inhibitor (ICI) selection. At a recent OncLive workshop, faculty favored cemiplimab monotherapy at PD-L1 ≥80%, citing its notably lower rash rates. Meanwhile, KEAP1-mutated disease remains a critical unmet need with near-zero response rates across all regimens.
When it comes to picking the right immunotherapy for metastatic non–small cell lung cancer (NSCLC), oncology experts are increasingly looking beyond survival curves. At a recent OncLive Scientific Interchange and Workshop, faculty agreed that PD-L1 expression level, tumor histology, and adverse effect profiles should all factor into frontline immune checkpoint inhibitor (ICI) selection — especially for patients without actionable driver mutations.
For high PD-L1 expressers (TPS ≥80%), the panel largely favored cemiplimab monotherapy, pointing to 6-year EMPOWER-Lung 1 data showing a median overall survival of 26.1 months and a strikingly low rash rate of just 1.1% — compared to 11% with pembrolizumab and 18.5% with atezolizumab. For PD-L1–negative disease, CTLA-4 inhibitor–based combinations (CheckMate 227/9LA) were preferred, though KEAP1 and STK11 mutations were flagged as prognostic rather than validated predictive biomarkers.
Key Takeaways:
Why it matters: As more ICI options reach the frontline, individualized treatment selection — driven by biomarkers, histology, and tolerability — is becoming the standard. Closing the gap for KEAP1-mutated and biomarker-negative never-smokers remains one of thoracic oncology's most pressing challenges.
