Results from an exploratory analysis of the Phase II LCMC3 trial showed that patients with resectable Stage IB-IIIB non-small cell lung cancer (NSCLC) who received adjuvant atezolizumab following neoadjuvant atezolizumab and resection had improved disease-free survival compared with those who were not administered adjuvant atezolizumab. These findings, presented during the 2023 European Lung Cancer Congress, also demonstrated a trend toward improved overall survival among patients who underwent adjuvant atezolizumab (Abstract 145MO).
"Neoadjuvant chemoimmunotherapy (IO) treatment without adjuvant treatment in CheckMate 816 has shown to improve pathologic responses and event-free survival outcomes," noted study author David P. Carbone, MD, PhD, the Barbara J. Bonner Chair in Lung Cancer Research and Director of the James Thoracic Center at The James Ohio State University Comprehensive Cancer Center. "However, it is completely unclear what the role of adjuvant immunotherapy is after neoadjuvant immunotherapy and there is no current study testing the role of adjuvant IO."
LCMC3 (NCT02927301) is an open-label, single-arm, Phase II study of neoadjuvant followed by optional adjuvant atezolizumab (anti-PD-L1) in resectable NSCLC. The primary endpoint-major pathological response (MPR)-was met with an observed MPR rate of 20 percent after neoadjuvant atezolizumab in patients without EGFR or ALK alterations who underwent surgery (Nature Med 2022; doi: 10.1038/s41591-022-01962-5).
Carbone and colleagues report updated disease-free survival, overall survival, and safety data from patients who received adjuvant atezolizumab versus those who did not.
Methods & Findings
Patients eligible for this study included those 18 years or older who had Stage IB-IIIA or select IIIB NSCLC, as well as an ECOG performance status of 0-1. The primary endpoint was major pathologic response (<=10% viable tumor cells). Secondary endpoints included pathologic response by PD-L1 and radiographic response by PD-L1, TMB, neoantigen, and GEP. Disease-free survival, overall survival, and biomarkers were exploratory endpoints. Safety was also examined during the adjuvant phase.
Study participants received neoadjuvant atezolizumab (1,200 mg IV for <=2 cycles) followed by surgery. Individuals without disease progression had the option to undergo adjuvant atezolizumab every 3 weeks for <=12 months. With a data cutoff of October 21, 2022, the primary efficacy population included 137 patients without EGFR/ALK alterations who had surgery and MPR assessment. Of those, 53 (39%) received adjuvant atezolizumab and 84 (61%) did not.
The baseline characteristics between these two groups were generally well-balanced, according to Carbone. However, he did note that patients who received adjuvant atezolizumab had a higher rate of squamous NSCLC (47% vs. 31%). They were also more likely to have a PD-L1 tumor proportion score (TPS) of 50 percent or higher (40% vs. 27%) and MPR status (42% vs. 8%) when compared to their counterparts who did not receive adjuvant atezolizumab. Study authors reported an updated 3-year disease-free survival and overall survival rate for the entire cohort of 72 percent and 82 percent, respectively. Disease-free and overall survival rates for Stage I/II were 75 percent and 82 percent, and 68 percent and 81 percent for Stage III.
In the MPR-evaluable population, the 3-year disease-free survival rate was 83 percent for those who were given adjuvant atezolizumab versus 64 percent for those who did not receive this treatment. Among patients without MPR (n=108), Carbone reported a 3-year disease-free survival of 80 percent for individuals who underwent adjuvant atezolizumab compared with 62 percent for those who did not. Three-year overall survival was 87 percent and 75 percent, respectively.
Carbone reported no unexpected safety findings. Among patients in the adjuvant atezolizumab safety population (n=57), any-grade adverse events (AEs) were observed in 96 percent of patients, including Grade 3/4 (40%) and Grade 5 (5%) adverse events. Treatment-related adverse events of any grade were reported in 63 percent of patients. Twenty-one percent had a Grade 3 treatment-related adverse event. Study authors reported that 23 percent of patients experienced any-grade AEs that led to treatment discontinuation, including 19 percent with Grade 3/4 (19%) and Grade 5 (2%) adverse events.
Immune-mediated adverse events were seen in 46 percent of patients treated with adjuvant atezolizumab. This included 16 percent with a Grade 3/4 event. Study authors reported that 33 percent of patients experienced any-grade immune-mediated treatment-related adverse events with 16 percent being Grade 3/4.
Significance & Implications
This exploratory analysis suggests that LCMC3 patients with resectable NSCLC who received adjuvant atezolizumab may have improved disease-free survival and showed a trend toward improved overall survival when compared with those who did not receive adjuvant atezolizumab, according to Carbone.
"The non-MPR subgroup also showed a trend toward improved disease-free survival and overall survival in patients who received adjuvant atezolizumab," he said, while also emphasizing that adjuvant atezolizumab was well-tolerated with no new safety concerns. "This single-arm study showed that outcomes were better than anticipated in patients who received adjuvant atezolizumab, which may prompt further studies of IO monotherapy," Carbone concluded.
Catlin Nalley is a contributing writer.