Which anti-PD-1 regimen showed the best survival for non-squamous non-small cell lung cancer?
For advanced non-squamous non-small cell lung cancer (nsNSCLC) without EGFR or ALK alterations, several anti-PD-1 regimens are available. A 2025 network meta-analysis and a phase III trial suggest that prolgolimab plus chemotherapy may offer the best overall survival, though pembrolizumab and cemiplimab plus chemotherapy also perform well. The choice depends on individual factors and drug availability.
What the research says
A 2025 network meta-analysis of 15 phase III trials found that prolgolimab + chemotherapy, pembrolizumab + chemotherapy, and cemiplimab + chemotherapy had the highest probability of being the best for overall survival (SUCRA 0.80-0.94) regardless of PD-L1 expression 1. For progression-free survival, nivolumab + bevacizumab + chemotherapy and atezolizumab + bevacizumab + chemotherapy ranked highest (SUCRA 0.91-0.96) 1. The phase III DOMAJOR trial specifically tested prolgolimab + pemetrexed + platinum chemotherapy versus placebo + chemotherapy in 292 patients with advanced non-squamous NSCLC. Median overall survival was not reached in the prolgolimab group versus 14.6 months in the placebo group (HR 0.51; p=0.0001), and the benefit was independent of PD-L1 status 7. The PERLA phase II trial directly compared dostarlimab + chemotherapy versus pembrolizumab + chemotherapy in 243 patients with metastatic non-squamous NSCLC. Overall response rate was 45% for dostarlimab and 39% for pembrolizumab, with median progression-free survival 8.8 vs 6.7 months (HR 0.70) and median overall survival 19.4 vs 15.9 months (HR 0.75), though the OS difference was not statistically significant 6. A real-world retrospective study of four PD-1 inhibitors in nonsquamous NSCLC found that second-line or later camrelizumab was associated with a higher risk of disease progression (HR 2.29) and death (HR 3.14) compared to pembrolizumab 3. For patients with EGFR-mutated non-squamous NSCLC who progressed on EGFR tyrosine-kinase inhibitors, the ORIENT-31 trial showed that sintilimab plus bevacizumab biosimilar plus chemotherapy improved progression-free survival compared to chemotherapy alone 5.
What to ask your doctor
- Which anti-PD-1 regimen has the best evidence for my specific PD-L1 expression level and tumor genetics?
- Would prolgolimab plus chemotherapy be available to me, and what are its potential side effects?
- How do the survival benefits of pembrolizumab or cemiplimab plus chemotherapy compare with prolgolimab in my case?
- If I have an EGFR mutation, is sintilimab plus bevacizumab and chemotherapy a suitable option after tyrosine-kinase inhibitor failure?
- What are the risks of adding bevacizumab to an anti-PD-1 regimen, especially regarding bleeding or blood clots?
This question is drawn from common patient questions about this topic and answered using cited medical research. We do not provide individualized advice.