Pembrolizumab plus chemotherapy for metastatic NSCLC with programmed cell death ligand 1 tumor proportion score <1%: pooled analysis of outcomes after five years of follow-up
Summary. Background. This study presents the results of a pooled analysis of patients with previously untreated metastatic non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) <1%. The patients participated in phase III clinical trials evaluating the use of pembrolizumab in combination with chemotherapy compared to placebo + chemotherapy. Methods. This pooled analysis included individual patient data from the global KEYNOTE-189 study (NCT02578680) and Japan extension (NCT03950674) study, which focused on metastatic non-squamous NSCLC without EGFR or ALK mutations. It also incorporated data from the KEYNOTE-407 trial (NCT02775435) and China extension (NCT03875092) study of metastatic squamous NSCLC. Patients received pembrolizumab or placebo combined with pemetrexed and cisplatin or carboplatin in the KEYNOTE-189 study. In the KEYNOTE-407 trial, patients were treated with pembrolizumab or placebo in combination with carboplatin and paclitaxel or nab-paclitaxel. PD-L1 expression levels were centrally assessed using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, USA). Results. A total of 442 patients were included in this analysis (255 patients received pembrolizumab + chemotherapy, and 187 received chemotherapy alone). The median follow-up duration was 60.7 months (range 49.9–72.0 months). The combination of pembrolizumab and chemotherapy resulted in improved overall survival (OS) (hazard ratio (HR) = 0.64; 95% confidence interval (CI) 0.51–0.79) and progression-free survival (PFS) (HR=0.66; 95% CI 0.54–0.81) compared to chemotherapy alone. The 5-year OS rates were 12.5% (95% CI 8.6–17.3%) and 9.3% (95% CI 5.6–14.1%) in the respective groups. Treatment-related adverse events (AEs) of grades 3–5 were observed in 59.1% of patients in the pembrolizumab + chemotherapy group and 61.3% in the chemotherapy-only group. Conclusion. The five-year follow-up results confirm that the combination of pembrolizumab and chemotherapy provides significant and durable survival benefits compared to chemotherapy alone for patients with previously untreated metastatic NSCLC with PD-L1 TPS <1%. These findings support the use of pembrolizumab + chemotherapy as the standard treatment approach for this patient population.
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