Atezolizumab Before and After Chemoradiation: Novel Plan for Unresectable Stage III NSCLC

By: Celeste L. Dixon
Posted: Wednesday, August 28, 2024

Neoadjuvant use of the monoclonal antibody atezolizumab with chemoradiotherapy may prove to be even more clinically effective than adjuvant immunotherapy in treating unresectable stage III non–small cell lung cancer (NSCLC). Thomas E. Stinchcombe, MD, of Duke Cancer Institute, Durham, North Carolina, and colleagues reported the results of their 62-patient, single-cohort, nonrandomized phase II AFT-16 trial in JAMA Oncology. They suggested further study in this area using randomized clinical trials.

The disease control rate for neoadjuvant atezolizumab at 12 weeks, the primary endpoint, was 74.2%. The median progression-free survival was 30 months; the median overall survival was not reached. The 24-month overall survival rate was 73.7%, and the overall response rate was 66.2%.

Regarding safety, 17 patients (27.4%) experienced grade 3 or higher immune-related adverse events; this included one with grade 5 pneumonitis and one with grade 4 Guillain-Barré syndrome. A total of 30 patients (48.4%) experienced grade 3 or higher treatment-related adverse events.

All patients (median age, 63.9 years) enrolled between 2018 and 2019; data were locked in March 2023. They were treatment-naive, had a good performance status, and received four 21-day cycles of atezolizumab (1,200 mg intravenously on day 1 of each cycle). If they had no tumor progression, they continued to chemoradiotherapy (60 Gy to involved fields) concurrently with weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m²). That was followed by planned consolidation carboplatin (AUC = 6) and paclitaxel (200 mg/m²) for two 21-day cycles. If no disease progression occurred, they continued on atezolizumab to complete 1 year of therapy.

Furthermore, the authors added, a hypothesis-generating analysis comparing the findings from AFT-16 with those of the monoclonal antibody durvalumab in the PACIFIC trial (in patients after chemoradiotherapy who were eligible for immunotherapy) “may support ongoing development of the neoadjuvant immune checkpoint inhibitor strategy in unresectable stage III NSCLC.”

Disclosure: For full disclosures of the study authors, visit JAMANetwork.com.

JAMA Oncology

---