Atezolizumab Extends DFS in PD-L1+ Early NSCLC

The Phase III IMpower010 study (NCT02486718) demonstrated a significant disease-free survival (DFS) advantage for adjuvant atezolizumab compared to best supportive care after platinum-based chemotherapy in patients with PD-L1 tumor cells (TC) ≥1% (by SP263) in stage II-IIIA non-small cell lung cancer (NSCLC), as reported in Lancet 2021 by Felip et al. Additionally, high tissue tumor mutational burden (TMB-H) has been linked to positive clinical responses to immune checkpoint inhibitors in various indications.

E. FELIP  and her research team aimed to present the extrapolatory report of DFS in resected  II-IIIA  NSCLC patients.

Patients underwent 1 to 4 cycles of cisplatin-based doublet chemotherapy post-resection, followed by randomization (1:1) for either 16 cycles of atezolizumab 1200 mg Q3W or best supportive care (BSC). Using whole exome sequencing data from the primary DFS analysis of IMpower010 (cutoff: January 21, 2021), tumor mutational burden (TMB) was determined, with TMB-H defined as above the median and TMB-L as below the median. PD-L1 expression levels were categorized using the SP263 immunohistochemistry assay as negative (TC <1%) or positive (TC ≥1%).

Among the TMB-evaluable patients in the stage II-IIIA population (n=549/882), baseline characteristics were well-matched (<10% difference) between treatment arms (atezolizumab: n=277; BSC: n=272). Median TMB stood at 6.23 mutations/Mb, with 273 patients having TMB-H tumors (atezolizumab: n=144; BSC: n=129) and 276 patients having TMB-L tumors (atezolizumab: n=133; BSC: n=143). 

The analysis showed that TMB-H was more prevalent in the PD-L1-positive subgroup than the PD-L1-negative subgroup (P=0.072). High TMB was prognostic for DFS in both atezolizumab (TMB-H vs TMB-L: HR, 0.53 [95% CI: 0.36, 0.78]) and BSC arms (TMB-H vs TMB-L: HR, 0.62 [95% CI: 0.44, 0.89]), with median DFS not reached for TMB-H subgroups. However, TMB did not predict atezolizumab treatment effects on DFS, as both TMB-H and TMB-L displayed similar efficacy enrichment in PD-L1-positive compared to PD-L1-negative subgroups.

The study found that despite the prognostic significance of baseline TMB in this patient cohort, the exploratory analysis indicates that adjuvant atezolizumab is linked to enhanced DFS in the PD-L1-positive stage II-IIIA population, regardless of TMB status. The research was sponsored by Hoffmann-La Roche. 

Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/918

Clinical Trial: https://clinicaltrials.gov/study/NCT02486718

Felip E, Srivastava M, Reck M., et al.(2023) “IMpower010: Exploratory Analysis of Tumour Mutational Burden and Disease-Free Survival with Adjuvant Atezolizumab in NSCLC’’ Presented at IASLC, 2023 World Conference on Lung Cancer, Singapore