While overall survival (OS) could not yet be formally tested in the intent-to- treat (ITT) population, the first interim analysis of OS with deaths in 25% of patients included in the IMpower010 study, showed OS improvement in favour of atezolizumab versus best supportive care (BSC) in the stage II-IIIA resected non-small cell lung cancer (NSCLC). The OS benefit with atezolizumab versus BSC was strongest in the stage II-IIIA PD-L1 TC ≥50% population.
No new safety signals were identified with 13 months’ additional follow-up. The results from the first pre-specified interim analysis of OS in the IMpower010 study are reported by Dr. Enriqueta Felip of the Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital in Barcelona, Spain, and colleagues in the Annals of Oncology on 17 July 2023.
The authors wrote in the background that recommended treatment for patients with early-stage resectable NSCLC is surgery, which has been associated with 5-year survival rates ranging from 41% in patients with stage IIIA NSCLC to 92% in those with stage IA1 disease. To improve these outcomes, adjuvant treatment is given to treat micrometastatic disease and prevent recurrence.
Adjuvant cisplatin-based doublet chemotherapy became the standard of care for resected early-stage NSCLC in 2004, but the 5-year survival rates with adjuvant chemotherapy are only 4-5% higher than with observation. In patients with EGFR mutations, osimertinib is now the standard-of-care adjuvant treatment, as monotherapy or after adjuvant chemotherapy. Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of advanced NSCLC and subsequently, interest has turned to evaluating their safety and efficacy in neoadjuvant and adjuvant settings.
IMpower010 demonstrated significantly improved primary endpoint, disease-free survival (DFS) with adjuvant atezolizumab versus BSC following platinum-based chemotherapy in the PD-L1-positive and all stage II-IIIA NSCLC populations, at the DFS interim analysis. Results of the first interim analysis of OS are reported in the latest article published in the Annals of Oncology.
IMpower010 is a phase III, open-label, 1:1 randomised study with 16 cycles of atezolizumab 1200 mg q3w versus BSC after 1-4 cycles of adjuvant platinum-based chemotherapy in adult patients with completely resected stage IB (≥4 cm)-IIIA NSCLC. Key secondary endpoints included OS in the stage IB-IIIA ITT population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay).
At a median of 45.3 months’ follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 patients (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable. The stratified hazard ratio (HR) was 0.995 (95% confidence interval [CI] 0.78-1.28). The stratified OS HRs were 0.95 (95% CI 0.74-1.24) in the stage II-IIIA, 0.71 (95% CI 0.49-1.03) in the stage II-IIIA PD-L1 TC ≥1%, and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% populations.
When the patients with known EGFR or ALK alterations were excluded from the stage II-IIIA PD-L1 TC ≥50% subpopulation, the OS results remained consistent. No OS improvement in favour of atezolizumab was seen versus BSC in the ITT or stage II-IIIA populations, and no OS benefit was seen with atezolizumab in the stage II-IIIA PD-L1 TC <1% population. However, due to the exploratory nature of the subgroup analyses and lack of formal testing, these data should be interpreted with caution.
Atezolizumab-related adverse event incidences remained unchanged since the previous analysis with grade 3/4 observed in 10.7% and grade 5 in 0.8% of patients.
The authors commented that although OS data remain immature for the ITT population and IMpower010 was not powered to show differences in treatment effects in patient subgroups, these exploratory OS data indicate a positive trend in favour of atezolizumab versus BSC in patients with resected stage II-IIIA PD-L1 TC ≥1% NSCLC, primarily driven by the PD-L1 TC ≥50% subgroup. No new safety signals were identified with 13 months’ additional follow-up. IMpower010 will continue until the final DFS analysis, with further OS follow-up and analyses in the ITT and other subpopulations planned.
Several other phase III clinical studies of adjuvant PD1/PD-L1 inhibitors in resectable stage IB-IIIA NSCLC are in progress, including PEARLS/KEYNOTE-091 testing pembrolizumab versus placebo, BR.31 testing durvalumab versus placebo, ANVIL testing nivolumab, and ALCHEMIST testing pembrolizumab plus platinum doublet chemotherapy versus pembrolizumab following chemotherapy versus observation following chemotherapy. Unlike in IMpower010, adjuvant chemotherapy before ICI is permitted, but not mandatory in the first three studies.
IMpower010 study was funded by F. Hoffmann-La Roche.
Felip E, Altorki N, Zhou C, et al. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Annals of Oncology; Published online 17 July 2023. DOI: https://doi.org/10.1016/j.annonc.2023.07.001