Combination Therapy Proves More Effective in NSCLC Compared With Chemotherapy

Combination therapies are promising methods of treating non–small cell lung cancer (NSCLC), with meta-analyses presented at the CHEST 2025 Annual Meeting, held in Chicago, Illinois, from October 19 to October 22, 2025, proving that combination therapies that include nivolumab or amivantamab are more effective in improving overall survival (OS) and progression-free survival (PFS) in those living with NSCLC.

The efficacy of nivolumab plus ipilimumab compared with chemotherapy alone was evaluated through a meta-analysis,1 using HRs to determine the efficacy. A random-effects model was utilized to pool all data, and heterogeneity was evaluated to assess variability.

Combination therapies featuring immune checkpoint inhibitors were more effective in NSCLC in meta-analyses | Image credit: Sebastian Kaulitzki - stock.adobe.com

A significant survival benefit was found with nivolumab plus ipilumumab when comparing the combination therapy to chemotherapy alone. The pooled HR was 0.70 (95% CI, 0.60-0.82), which indicates a 30% reduction in risk of death. The risk of disease progression was also found to be reduced when using the combination therapy, with an HR of 0.62 (95% CI, 0.53-0.72). Significant heterogeneity was not observed between the studies.

The researchers concluded that the combination of nivolumab plus ipilimumab was more effective in improving OS and PFS in patients with NSCLC. They noted that these results could point to the potential of controlling the disease for a prolonged period of time and indicate that immune checkpoint inhibitors should be considered first-line therapy for patients with NSCLC.

Similar results were found when evaluating a separate combination therapy of amivantamab plus lazertinib compared with osimertinib plus chemotherapy.2 Patients treated with this combination therapy had EGFR-mutated NSCLC. The researchers performed a systematic review due to previous promising results in treating the condition with tyrosine kinase inhibitors like lazertinib.

PubMed, Embase, and Cochrane Library were searched before including 4 studies that were published through December 2024. PFS, OS, and objective response rate (ORR) were evaluated alongside the safety of the combination therapy.

PFS was greatly improved when using lazertinib in combination with amivantamab with an HR of 0.64 (95% CI, 0.57-0.72) compared with osimertinib plus chemotherapy. OS was also significantly improved in those who took the combination therapy, with an HR of 0.58 (95% CI, 0.49-0.68). The ORR in the combination arm was 0.97 (95% CI, 0.86-1.08), significantly higher than that seen in the comparator arm. Rash, fatigue, anemia, and hepatotoxicity were the only grade 3 and 4 adverse events reported by the participants of the study.

The researchers concluded that the combination of both amivantamab and lazertinib was more effective at improving OS, PFS, and ORR when compared with the monotherapy of osimertinib plus chemotherapy, specifically in patients with the EGFR mutation and NSCLC. Although they warned of the higher toxicity profile that comes with this treatment and urged physicians to monitor and manage adverse events closely, the researchers reaffirmed that these results could redefine how physicians approach first-line treatment in these patients.

References

1. Bacha Z, Henna F, Muhammad UA, et al. Efficacy of nivolumab plus ipilimumab vs chemotherapy in non–small cell lung cancer: a systematic review and meta-analysis. Presented at: CHEST 2025 Annual Meeting; October 19-22, 2025; Chicago, IL.

2. Elemian S, Habbas A, Touza M, et al. Efficacy and safety of amivantamab plus Lazertinib vs Osimertinib and chemotherapy in EGFR-mutant non–small cell lung cancer: a systematic review and meta-analysis. Presented at: CHEST 2025 Annual Meeting; October 19-22, 2025; Chicago, IL.