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Thursday, September 22, 2022

​Overall Survival Benefit in Resected Non-Small Cell Lung Cancer

By Mark L. Fuerst

Non-small cell lung cancer (NSCLC) patients treated with atezolizumab show a trend toward overall survival (OS) benefit, particularly those who have high programmed death ligand-1 (PD-L1) expression, according to a new interim analysis presented at the IASLC 2022 World Conference on Lung Cancer (Abstract PL03.09). An OS trend favored atezolizumab over best supportive care (BSC) in those with PD-L1 level of more than 1 percent Stage II-IIIA population (OS HR=0.71). The highest magnitude of OS improvement was observed in patients with Stage II-IIIA disease whose tumors expressed PD-L1 in 50 percent or higher (HR=0.43). 

“This OS analysis shows a promising trend in favor of atezolizumab over BSC in the PD-L1 ≥1 percent, Stage II–IIIA population and a clinically meaningful improvement in the PD-L1 ≥50 percent, Stage II–IIIA population, with the OS improvements observed across most subgroups. No separation was observed for the intent-to-treat (ITT) population or the all-randomized, Stage II–IIIA populations. We will continue to follow patients in this study as data mature," said lead author Enriqueta Felip, MD, PhD, Head of the Lung Cancer Unit in the Oncology Department at Vall d'Hebron University Hospital, Barcelona, Spain.

Previously, the IMpower010 trial showed a statistically significant disease-free survival (DFS) benefit with adjuvant atezolizumab compared with BSC in patients with resected NSCLC following platinum-based chemotherapy (2021; doi: 10.1200/JCO.2021.39.15_suppl.8500). Based on these findings, atezolizumab was approved as adjuvant treatment after complete resection and platinum-based chemotherapy in patients with PD-L1 ≥1 percent Stage II-IIIA NSCLC in the United States, China, and other countries, as well as in PD-L1 ≥50 percent Stage II-IIIA NSCLC in the European Union (excluding EGFR/ALK-positive tumors) and other countries.

The key secondary OS endpoint was not mature at the IMpower010 DFS interim analysis. Felip presented data evaluating OS and safety with 13 months of additional follow-up. At the clinical cutoff date of April 18, 2022, median follow-up was 45 months and 25 percent of patients had died. The new analysis constitutes the first pre-specified OS interim analysis; OS in the ITT population will only be formally tested if DFS in that population reaches statistical significance at the final DFS analysis. 

Eligible patients had completely resected Stage IB-IIIA NSCLC (AJCC/UICC v7) and ECOG PS 0-1. They received 1-4, 21-day cycles of cisplatin-based doublet chemotherapy (enrollment phase) and were subsequently randomized to receive 16 cycles of atezolizumab 1,200 mg once every 3 weeks or BSC (randomization phase).

The primary endpoint was DFS hierarchically tested in three prespecified populations (PD-L1 ≥1% Stage II-IIIA population, all randomized Stage II-IIIA population, and ITT population (Stage IB-IIIA); secondary endpoints included OS among the ITT population and safety outcomes.

Adverse events of Grade 3-4 occurred in 22 percent of the atezolizumab arm and 11.5 percent of the BSC arm and led to atezolizumab discontinuation in 18.2 percent of patients. Grade 5 treatment-related adverse events occurred in 0.8 percent of patients who received atezolizumab and none in the BSC arm. Adverse events of special interest occurred in 52.1 percent of atezolizumab-treated patients; 7.9 percent were Grades 3-4.

“In a prespecified interim analysis of OS from the Phase III IMpower010 trial, adjuvant atezolizumab following complete resection and adjuvant chemotherapy suggests a trend toward OS benefit in patients with Stage II-IIIA NSCLC with PD-L1 ≥1 percent versus BSC in this patient population. A trend toward OS benefit was also seen in patients with Stage II-IIIA NSCLC with PD-L1 ≥50 percent. No OS benefit was observed in all-randomized Stage II-IIIA or ITT (Stage IA-III) patient populations," Felip noted. “The safety profile of adjuvant atezolizumab at median follow-up of 45 months was similar to earlier data; no new or unexpected adverse events were observed after an additional 13 months of follow-up."

These data continue to support previous findings and the currently approved use of atezolizumab as adjuvant treatment for patients with Stage II-IIIA NSCLC that is PD-L1 positive after complete resection and adjuvant chemotherapy, she said. “Additional follow-up is required for final DFS analysis and subsequent hierarchical OS analysis," Felip concluded.

Mark L. Fuerst is a contributing writer.