Comparative Efficacy of Neoadjuvant Nivolumab Plus Chemotherapy versus Conventional Comparator Treatments in Resectable Non-Small-Cell Lung Cancer: A Systematic Literature Review and Network Meta-Analysis

Simple Summary Lung cancer is the leading cause of cancer deaths worldwide. Surgery, with or without neoadjuvant or adjuvant chemotherapy has historically been the mainstay of treatment for resectable non-small-cell lung cancer (rNSCLC). However, as many as half of those treated still die of the disease. Immune checkpoint inhibitors are changing the landscape of treatment both in the neoadjuvant and adjuvant rNSCLC settings in many countries. In this review and analysis, outcomes among patients treated in the neoadjuvant setting (i.e., prior to surgery) with the immune checkpoint inhibitor nivolumab combined with chemotherapy were compared to those of patients treated with the historical standard of care treatments, using data from published studies. The results of this evidence synthesis show that neoadjuvant nivolumab when combined with chemotherapy improves the likelihood of event-free survival and a pathological complete response for patients relative to traditional treatments, specifically, surgery, alone or in combination with neoadjuvant or adjuvant (i.e., after surgery) chemotherapy, and neoadjuvant chemoradiotherapy.Abstract Background: This study aimed to estimate the relative efficacy of neoadjuvant nivolumab in combination with chemotherapy (neoNIVO + CT) compared to relevant treatments amongst resectable non-metastatic non-small-cell lung cancer (rNSCLC) patients. Methods: Treatment comparisons were based on a network meta-analysis (NMA) using randomized clinical trial data identified via systematic literature review (SLR). The outcomes of interest were event-free survival (EFS) and pathological complete response (pCR). NeoNIVO + CT was compared to neoadjuvant chemotherapy (neoCT), neoadjuvant chemoradiotherapy (neoCRT), adjuvant chemotherapy (adjCT), and surgery alone (S). Due to the potential for effect modification by stage, all-stage and stage-specific networks were considered. Fixed-effect (FE) and random-effects Bayesian NMA models were run (EFS = hazard ratios [HR]; pCR = odds ratios [OR]; 95% credible intervals [CrI]). Results: Sixty-one RCTs were identified (base case = 9 RCTs [n = 1978 patients]). In the all-stages FE model, neoNIVO + CT had statistically significant EFS improvements relative to neoCT (HR = 0.68 [95% CrI: 0.49, 0.94]), S (0.59 [0.42, 0.82]), adjCT (0.66 [0.45, 0.96]), but not relative to neoCRT (HR = 0.77 [0.52, 1.16]). NeoNIVO + CT (5 RCTs) had statistically significant higher odds of pCR relative to neoCT (OR = 12.53 [5.60, 33.82]) and neoCRT (7.15 [2.31, 24.34]). Stage-specific model findings were consistent. CONCLUSIONS: This NMA signals improved EFS and/or pCR of neoNIVO + CT relative to comparators among patients with rNSCLC.