Does atezolizumab improve OS in patients with resected NSCLC and PD-L1 ≥1 percent?

The first interim analysis of the phase III IMpower010 trial suggests an overall survival (OS) benefit with atezolizumab compared with best supportive care (BSC) in patients with resected non-small cell lung cancer (NSCLC) with PD-L1* tumour cell expression ≥1 percent.

“OS benefit favouring atezolizumab was not seen in the all-randomized stage II–IIIA or ITT** populations,” presented study author Dr Enriqueta Felip from the Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain.

“[However,] this OS analysis shows a promising trend in favour of atezolizumab over BSC in the PD-L1 tumour cell ≥1 percent, stage II–IIIA population and a clinically meaningful improvement in the PD-L1 tumour cell ≥50 percent, stage II–IIIA population, with the OS improvements observed across most subgroups,” she highlighted at WCLC 2022.

Participants (n=1,005) had completely resected stage IB (tumours ≥4 cm)–IIIA NSCLC and an ECOG performance status of 0–1. Following receipt of one to four 21-day cycles of cisplatin-based doublet chemotherapy***, they were randomized 1:1 to receive 16 cycles of atezolizumab 1,200 mg Q3W or BSC.

At a median follow-up of 45.3 months, there was a trend toward improved OS with atezolizumab compared with BSC in patients with stage II–IIIA disease and PD-L1 tumour cell ≥1 percent (median not reached [NR] in both groups; hazard ratio [HR], 0.71, 95 percent confidence interval [CI], 0.49–1.03), with 60-month OS of 76.8 percent vs 67.5 percent. [WCLC 2022, session PL03.09; abstract 2332]

This OS benefit was not observed in the overall population of patients with stage II–IIIA NSCLC (median NR in both groups; HR, 0.95, 95 percent CI, 0.74–1.24) or in the ITT population of all patients with stage IB–IIIA NSCLC (median NR in both groups; HR, 0.995, 95 percent CI, 0.78–1.28).

The greatest OS benefit with atezolizumab vs BSC was observed in patients with stage II–IIIA disease and PD-L1 tumour cell ≥50 percent (median NR in both groups; HR, 0.42, 95 percent CI, 0.23–0.78; estimated 60-month OS: 84.8 percent vs 67.5 percent [excluding EGFR+ and ALK+]; HR, 0.43, 95 percent CI, 0.24–0.78 [including EGFR+ and ALK+]).

“After an additional 13 months of follow-up, the safety profile remains broadly unchanged, with no new or unexpected safety signals, and is consistent with the known safety profile of atezolizumab,” noted Felip.

In this updated analysis, grade 3–4 adverse events (AEs) were reported in 22.0 percent vs 11.5 percent of atezolizumab vs BSC recipients and were considered treatment related in 10.7 percent vs 0 percent. Serious AEs occurred in 17.8 percent vs 8.5 percent and were considered treatment related in 7.5 percent vs 0 percent. Grade 5 treatment-related AEs occurred in 0.8 percent vs 0 percent. In atezolizumab recipients, AEs led to treatment interruption in 28.7 percent and withdrawal of any treatment in 18.2 percent. Grade 3–4 AEs of special interest occurred in 7.9 percent vs 0.6 percent of atezolizumab vs BSC recipients.

“These data support the previously reported positive benefit-risk profile of adjuvant atezolizumab in PD-L1+ resected NSCLC and contribute to evidence supporting standard of care use,” said Felip. [Lancet 2021;398:1344-1357]

“With an event to patient ratio of 25 percent in the ITT population, the OS data are not mature, but are of clinical interest in this curative setting,” remarked Felip. Further follow-up of the population will continue for OS as well as DFS analysis.