IMpower010 highlights trend towards an overall survival benefit with atezolizumab in resected stage II-IIIA NSCLC
At the first interim analysis of overall survival (OS) in the IMpower010 study, presented at the IASLC WCLC 2022 meeting, an OS trend in favour of atezolizumab was observed in the PD-L1 TC ≥1% stage II-IIIA non-small cell lung cancer (NSCLC) population, but not in the all-randomised stage II-IIIA or intention-to-treat populations. No new safety signals were observed with an additional 13 months of follow-up of this study.
In IMpower010, adjuvant atezolizumab demonstrated a statistically significant disease-free survival (DFS) benefit versus best-supportive care (BSC) in resected non-small cell lung cancer (NSCLC) following platinum-based chemotherapy at the DFS interim analysis. Based on these findings, atezolizumab was approved in Europe as adjuvant treatment after resection and platinum-based chemotherapy in patients with PD-L1 TC≥50% stage II-IIIA NSCLC (excluding EGFR/ALK+). The key secondary overall survival (OS) endpoint was not mature at the IMpower010 DFS interim analysis but is of considerable clinical interest in this curative setting. The first pre-specified interim analysis of overall survival (OS) and safety has now been conducted at a median follow-up of 45.3 months.
IMpower010 enrolled 1,280 patients of whom 1,269 received up to four 21-day cycles of adjuvant chemotherapy (cisplatin, partnered with either pemetrexed, docetaxel, gemcitabine or vinorelbine). In total, 1,005 of these patients were subsequently randomised (1:1) to sixteen cycles of atezolizumab (1,200 mg Q3W), or best supportive care (BSC). All eligible patients had completely resected (4-12 weeks prior to enrolment) stage IB (≥4 cm)-IIIA NSCLC (per AJCC/UICC v7) and had an ECOG performance status of 0-1. The primary endpoint of investigator-assessed DFS and secondary endpoint of overall survival (OS) were tested hierarchically: first DFS in the PD-L1 tumour cell (TC) ≥1% (SP263) subgroup with Stage II-IIIA disease, if positive DFS in all randomised patients with stage II-IIIA disease, and finally DFS in the ITT population (stage IB-IIIA). Only if the latter analysis was positive, the OS could be tested in the ITT population.
At the clinical cut-off date (18 April 2022), median follow-up was 45 months and 25% of patients had died (ITT population; N= 1,005). An overall survival trend in favour of atezolizumab was observed in the PD-L1 TC ≥1% stage II-IIIA population (HR[95%CI]: 0.71[0.49-1.03]). The OS rates at 36 months and 60 months were 82.1% and 76.8% in the atezolizumab group, respectively, compared with 78.9% and 67.5% in the best supportive care group. Furthermore, there was a clinically meaningful improvement in the PD-L1 TC ≥50% population (HR[95%CI]: 0.43[0.24-0.78]). However, this trend in favour of atezolizumab was not observed in the all randomised stage II-IIIA population (HR[95%CI]: 0.95[0.74-1.24]) or the ITT population (HR[95%CI]: 0.995[0.78-1.28], p= 0.9661).
Treatment-related adverse events (TRAEs) of grade 3-4 occurred in 10.7% of patients the atezolizumab arm and 0% of the best supportive care arm. Grade 5 TRAEs occurred in 0.8% of patients who received atezolizumab and 0% in the best supportive care arm. Adverse events of special interest occurred in 52.1% of atezolizumab-treated patients, 7.9% were grades 3-4. Additionally, 28.7% and 18.2% of patients in the atezolizumab arm required a dose interruption or treatment withdrawal due to AEs vs. no patients in the control group.
At the time of this first pre-specified interim OS analysis, an OS trend in favour of atezolizumab was seen in the PD-L1 TC ≥1% stage II-IIIA population. This OS benefit favouring atezolizumab was not seen in the all-randomised stage II-IIIA or ITT populations. 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. 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. IMpower010 will continue to the final DFS analysis, with further OS follow-up and analyses.
Felip E, Altorki N, Vallieres E, et al. IMpower010: Overall Survival Interim Analysis of a Phase III Study of Atezolizumab vs Best Supportive Care in Resected NSCLC. Presented at IASLC WCLC 2022; Abstract PL03.09.