Efficacy and safety of immunotherapy in driver mutation-negative advanced non-small cell lung cancer: A systematic review and meta-analysis
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Jogender Kumar1, Shuvadeep Ganguly2, Parminder Kaur1
1Department of Pediatrics (Advanced Pediatrics Centre), Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
Background and objectives Despite substantial research on immunotherapy, its efficacy and safety in treating advanced non-small cell lung cancer (NSCLC) without identifiable driver mutations remain unclear. The objective of this review was to examine the efficacy and safety of immunotherapy, used as monotherapy or alongside chemotherapy, vs. chemotherapy alone in patients with advanced driver mutation-negative NSCLC. Methods A comprehensive literature search of PubMed, Embase, Scopus, and CENTRAL databases was conducted until December 2024. The protocol was registered in PROSPERO (CRD42024585050). Randomised controlled trials (RCTs) evaluating the efficacy and safety of immunotherapy, either as monotherapy or in combination with chemotherapy, compared with chemotherapy alone, were included. A random-effects meta-analysis was performed. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Results Twenty-three RCTs (n=14605 participants) were included. Immunotherapy (± chemotherapy) significantly improved overall survival [22 RCTs; 14,375 participants, hazard ratio (HR): 0.77; 95% Confidence interval (CI): 0.72-0.83] and progression-free survival (22 RCTs; 14,003 participants, HR: 0.67; 95% CI: 0.58-0.76) compared with chemotherapy alone. The objective response rate was also higher with immunotherapy (23 RCTs; 12,967 participants, RR 1.38, 95% CI: 1.24-1.54). No statistically significant differences were observed between the groups in terms of overall adverse event rates. Interpretation and conclusions Immunotherapy, whether administered alone or in combination with chemotherapy, provides significant survival benefits in patients with advanced driver mutation-negative NSCLC.
Insights
Immunotherapy, with or without chemotherapy, significantly improves survival for advanced non-small cell lung cancer (NSCLC) patients lacking driver mutations. This treatment approach demonstrates enhanced overall and progression-free survival with comparable safety to chemotherapy alone.
Area of Science:
- Oncology
- Immunotherapy
- Pulmonology
Background:
- Efficacy and safety of immunotherapy in advanced driver mutation-negative non-small cell lung cancer (NSCLC) are not fully understood.
- Immunotherapy is a promising treatment modality for various cancers, including NSCLC.
Purpose of the Study:
- To evaluate the efficacy and safety of immunotherapy (monotherapy or combination) versus chemotherapy alone in advanced driver mutation-negative NSCLC.
- To synthesize evidence from randomized controlled trials (RCTs) for robust conclusions.
Main Methods:
- Comprehensive literature search of major databases (PubMed, Embase, Scopus, CENTRAL) until December 2024.
- Random-effects meta-analysis of 23 RCTs (14,605 participants) comparing immunotherapy-based regimens with chemotherapy.
- Risk of bias and certainty of evidence assessed using Cochrane RoB 2 and GRADE frameworks.
Main Results:
- Immunotherapy (± chemotherapy) significantly improved overall survival (HR: 0.77; 95% CI: 0.72-0.83) and progression-free survival (HR: 0.67; 95% CI: 0.58-0.76).
- Higher objective response rates were observed with immunotherapy (RR: 1.38; 95% CI: 1.24-1.54).
- No significant differences in overall adverse event rates between immunotherapy and chemotherapy groups.
Conclusions:
- Immunotherapy, as monotherapy or in combination with chemotherapy, offers significant survival benefits for advanced driver mutation-negative NSCLC.
- The findings support immunotherapy as a valuable treatment option for this patient population.
- Safety profiles appear comparable between immunotherapy-based treatments and chemotherapy alone.
