Immunotherapy combined with chemotherapy versus chemotherapy alone as the first‐line treatment of PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous non‐small‐cell lung cancer: An updated systematic review and meta‐analysis

BACKGROUND: This meta‐analysis aimed to compare the efficacy of immunotherapy combined with chemotherapy versus chemotherapy alone as the first‐line therapy for patients with programmed death ligand‐1 (PD‐L1)‐negative and driver‐gene‐negative advanced nonsquamous non‐small‐cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible randomized trials were identified following the systematic search of PubMed, Cochrane Library, Embase, Web of Science, Wanfang Data, and China Knowledge Resource Integrated Database from January 2000 to June 2022. RESULTS: Seven trials involving 1132 patients with PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous NSCLC were included. Immunotherapy combined with chemotherapy showed significantly superior objective response rate (ORR) compared with chemotherapy alone (odds ratio 2.81, 95% confidence interval [CI] 1.69–4.65). Immunotherapy combined with chemotherapy also significantly prolonged the progression‐free survival (PFS) (hazard ratio [HR] 0.63, 95% CI 0.55–0.74, p < 0.001) and overall survival (OS) (HR 0.68, 95% CI 0.56–0.82, p < 0.001) of patients with PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous NSCLC compared to chemotherapy alone. In terms of ≥3 treatment‐related adverse events, patients receiving immunotherapy combined with chemotherapy were at higher risk than chemotherapy alone (OR 1.73, 95% CI 1.47–2.05). CONCLUSIONS: This meta‐analysis suggested that immunotherapy combined with chemotherapy yielded a better ORR, PFS, and OS, and a higher incidence of treatment‐related adverse events as the first‐line therapy for patients with PD‐L1‐negative and driver‐gene‐negative nonsquamous advanced NSCLC in comparison to chemotherapy alone. A rational treatment protocol should be selected according to the individual condition of the patients.