Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

Abstract

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer

“…Yang et al found that the OS and ORR of the chemotherapy plus cetuximab group were markedly better than those of the chemotherapy alone group, but the difference in PFS was not remarkable [3] . In another meta-analysis, Ilic [23] found that the OS of the chemotherapy plus necitumumab group was notably better than that of the chemotherapy alone group, but there were no notable differences in PFS or ORR, which is consistent with the results of our subgroup analysis. Consequently, the combination of an anti-EGFR-mAb with a platinum-based dual chemotherapy regimen is a reasonable strategy for the clinical treatment of advanced NSCLC.…”

“…Another meta-analysis to determine the efficacy of chemotherapy combined with cetuximab showed that cetuximab plus chemotherapy had more benefits for NSCLC than chemotherapy alone [22] . Moreover, a meta-analysis showed that the OS of necitumumab plus chemotherapy was significantly better than that of chemotherapy alone, but there were no remarkable differences in objective response rate (ORR) and PFS [23] . The limitations of these meta-analyses include that the trials included only one anti-EGFR-mAb, the sample sizes of patients were too small, and analysis of publication bias was lacking.…”