Research in context
Evidence before this study
We searched PubMed from Jan 1, 2010, to May 11, 2020, for clinical trials published in English using the search terms “neoadjuvant”, “lung cancer”, and “PD-L1” or “PD-1”. Our search yielded two studies. The first study described neoadjuvant nivolumab treatment in patients with stage I–IIIA non-small-cell lung cancer (NSCLC) with the primary endpoints of safety and feasibility; however, no survival data were reported. The second study assessed neoadjuvant atezolizumab plus chemotherapy for patients with stage II–IIIA NSCLC, and the authors identified no association between major pathological response and survival after a median of 1-year follow-up. Additionally, using the same search terms and date restrictions, we examined the websites of three major international conferences (American Society of Clinical Oncology, European Society for Medical Oncology, and World Conference on Lung Cancer) and ClinicalTrials.gov, and identified several ongoing phase 2 and phase 3 trials of different neoadjuvant immunotherapy approaches with estimated primary completion dates ranging from 2020 to 2024.
Added value of this study
To our knowledge, our study is the first published trial to assess the feasibility, safety, antitumour activity, and survival outcomes of neoadjuvant nivolumab plus standard chemotherapy in patients with resectable stage IIIA NSCLC. One of the main concerns regarding neoadjuvant therapy is risk of preoperative complications; however, we showed that treatment was well tolerated, was not associated with delays in surgery, and led to complete resection in all patients who had surgery. Our results showed that in this high-risk patient group, which included a high proportion of patients with multiple stage IIIA (N2) disease, favourable pathological responses and downstaging, and progression-free survival and overall survival at 24 months were observed after neoadjuvant nivolumab plus standard chemotherapy.
Implications of all the available evidence
Our results combined with existing evidence could support the addition of neoadjuvant nivolumab to platinum-based chemotherapy in patients with resectable stage IIIA NSCLC, and encourage the use of pathological response as an early surrogate endpoint for survival, while considering specific somatic mutations that might limit its survival-predictive value. These observations have important implications for future clinical trial design and could improve outcomes for patients with resectable stage IIIA NSCLC.