Clinical benefit of anti PD-1/PD-L1 plus chemotherapy versus chemotherapy alone in first-line treatment in advanced non-small cell lung cancer: A meta-analysis

Abstract

Background: First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Combination of anti-PD-1/PD-L1 to chemotherapy (CT) offers a new therapeutic option for this population. Methods: We performed a meta-analysis of randomized trials that compared PD-1/ PD-L1 inhibitor plus CT with CT alone in first line of treatment for advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. Results: The eight eligible studies included 4401 patients (3097 males, mostly smokers (81%), median age 64 years), with 3037 nonsquamous (69 %) and 1330 squamous tumours (30%). One study evaluated nivolumab+ CT (CheckMate 227), four studies evaluated atezolizumab +CT (IMpower 130,131,132 and 150), and three studies pembrolizumab +CT (Keynote 021, 189 and 407). The combination PD-1/PD-L1 inhibitor +CT was significantly associated with improvement of OS (hazards ratio [HR], 0.72; 95% CI 0.61-0.85; p<0.0001), PFS (HR, 0.63; 95% CI 0.58-0.68; p<0.0001) and ORR (relative ratio [RR], 2.08; 95% CI 1.69-2.55; p<0.0001), irrespective of PD-L1 expression level. For patients with low (<1%) or undetectable PD-L1 expression, OS benefit was statistically significant (HR, 0.75; 95% CI 0.63-0.89; p<0.0008). Conclusions: The combination of PD-1/PD-L1 inhibitor to chemotherapy, compared with chemotherapy alone, is associated with significantly improved OS, PFS, and ORR in first-line therapy in NSCLC. This strategy appears as a new standard of care for patients with untreated NSCLC, including for those with low or undetectable PD-L1 expression.