Immune checkpoint inhibitors, including atezolizumab, have been evaluated in several phase II trials for neoadjuvant therapy in resectable lung cancer, both with and without chemotherapy, such as the LCMC3 trial and CheckMate 816. Ongoing studies, including the IMpower030 trial, are further exploring their potential in early-stage disease. However, the application of these inhibitors as a neoadjuvant strategy prior to chemoradiation therapy (CRT) for unresectable non–small cell lung cancer (NSCLC) has not been extensively studied.
The clinical outcomes of administering atezolizumab both before and after CRT in patients with unresectable stage III NSCLC were evaluated in a phase II nonrandomized controlled trial published by Ross et al in JAMA Oncology.
Prof. Kouhen Fadila
Study Protocols
This phase II, single-cohort, nonrandomized controlled trial was conducted at 11 sites in the United States and enrolled 62 treatment-naive patients with pathologically confirmed, unresectable stage III NSCLC and a good performance status. Enrollment took place from January 2018, to July 2019, with data locked in March 2023. Participants received four cycles of atezolizumab (1,200 mg intravenously on day 1 of each 21-day cycle). Patients who did not experience tumor progression proceeded to CRT, consisting of 60 Gy to involved fields in combination with weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m²). Those without disease progression after CRT continued with consolidation therapy, including carboplatin (AUC = 6) and paclitaxel (200 mg/m²) for two additional 21-day cycles, followed by atezolizumab (1,200 mg every 21 days) for up to 1 year.
The primary endpoint of the study was the disease control rate at 12 weeks, with secondary endpoints including progression-free survival, overall survival, overall response rate, safety, and translational science outcomes.
Key Findings
The study included 62 patients with a median age of 63.9 years, of whom 51.6% were female. The disease control rate at 12 weeks was 74.2% (80% confidence interval [CI] = 65.7%–81.4%). The median progression-free survival was 30.0 months (95% CI = 15.8 months to not evaluable), and the median overall survival has not yet been reached. At the 24-month mark, the overall survival rate was 73.7% (95% CI = 63.4%–85.7%), with an overall response rate of 66.2%.
The authors observed that 27.4% of patients experienced grade 3 or higher immune-related adverse events, including one case of grade 5 pneumonitis and one case of grade 4 Guillain-Barré syndrome. Additionally, 48.4% of patients had grade 3 or higher treatment-related adverse events.
Despite these adverse events, the authors concluded that the neoadjuvant use of atezolizumab shows promising efficacy and a manageable safety profile. They advocated for further research through randomized clinical trials to better evaluate its potential benefits in this treatment context.
Prof. Kouhen Fadila is affiliated with Mohammed VI University of Sciences and Health (UM6SS), Casablanca, Morocco; the Radiotherapy Department, International University Hospital Sheikh Khalifa; and the Laboratory of Neurosciences and Oncogenetics, Neurooncology and Oncogenetic Team, Mohammed VI Center for Research & Innovation.
Disclosure: This study was supported by the Alliance Foundation Trials. For full disclosures of the study authors, visit jamanetwork.com.
