Atezolizumab efficacious across high PD-L1 expressers with stage II-IIIA NSCLC

A recent sub-analysis from the pivotal phase III IMpower 010 study demonstrates that patients with PD-L1 TC ≥ 50% stage II-IIIA non-small cell lung cancer derive a disease-free survival (DFS) benefit with atezolizumab versus best supportive care (BSC). Numerically, more distant and CNS relapses were seen with BSC. The tolerability profile of atezolizumab was in line with the overall population, demonstrating a positive benefit-risk profile.

IMpower010 is the first phase III immunotherapy study to demonstrate a significant disease-free survival (DFS) improvement in the adjuvant setting after platinum-based chemotherapy. At the interim DFS analysis, atezolizumab demonstrated a significant DFS benefit versus best supportive care (BSC) in the stage II-IIIA PD-L1 TC ≥1% population (stratified HR, 0.66; 95%CI: 0.50-0.88), with greatest benefit in the PD-L1 TC ≥50% subgroup (unstratified HR, 0.43; 95%CI: 0.27-0.68). At ELCC 2022, further analyses in the PD-L1 TC ≥50% stage II-IIIA NSCLC population were presented.

IMpower010 study design

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 BSC. All eligible patients had completely resected (4-12 weeks prior to enrolment) stage IB (≥4 cm)-IIIA NSCLC (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% (per 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. DFS in PD-L1 TC ≥50% (VENTANA SP263 assay) stage II-IIIA patients was a prespecified secondary endpoint; additional subgroup data reported are exploratory.

Results

Baseline characteristics were generally balanced for patients with PD-L1 TC ≥50% stage II-IIIA NSCLC as compared to the ITT population; median age was 62 years, 14% were never smokers, 46% had stage IIIA disease and an EGFR mutation was detected in approximately 6% of the cases. Furthermore, roughly 75% of the patients underwent a lobectomy. The median DFS in the PD-L1 TC ≥50% stage II-IIIA NSCLC population treated with atezolizumab was not reached and was 35.7 months for those patients in the control arm (HR[95%CI]: 0.43[0.27-0.68]). At three years, 73.8% of patients in the atezolizumab arm were still disease-free, as compared to only 48.6% in the BSC arm. Overall, the majority of patient subgroups benefitted from adjuvant atezolizumab. Furthermore, also when patients with known EGFR or ALK alterations were excluded from the analysis, DFS outcomes remain similar. Currently, exploratory OS data in these populations were immature and further follow-up is needed. Safety in PD-L1 TC ≥50% stage II-IIIA patients was consistent with that of the overall study population and the known safety profile of atezolizumab. No grade 5 adverse events (AEs) were reported in this population. AEs leading to discontinuation of atezolizumab were observed in 21 patients (19%).

A reduced overall risk of relapse was seen with atezolizumab (22% of patients) versus BSC (44% of patients), with some differences in relapse pattern by site. Initial disease relapse in this population was locoregional-only in 13% of patients in the atezolizumab-arm versus 15% in the BSC-arm and distant-only in 5% vs. 18%. Initial CNS-only relapse was seen in respectively 1% and 6% of patients. The median time to relapse was 18.1 months in the atezolizumab arm and 10.1 months in the BSC arm. Overall, in the PD-L1 TC ≥50% stage II-IIIA population, 19 relapsing atezolizumab-arm patients (76%) vs. 30 BSC-arm patients (60%) received subsequent systemic therapy (mostly chemotherapy, 60% vs. 32% and immunotherapy, 16% vs. 38%).

Conclusion

IMpower010 demonstrated a 57% reduction in the risk of disease recurrence or death with adjuvant atezolizumab versus BSC in the PD-L1 TC ≥50% stage II-IIIA population. The safety profile of atezolizumab in the PD-L1 TC ≥50% stage II-IIIA population was consistent with that of the stage I-IIIA population. More patients experienced relapse as their earliest DFS event with BSC than with atezolizumab in the PD-L1 TC ≥50% stage II-IIIA population. These findings in the PD-L1 TC ≥50% stage II-IIIA population build on the positive benefit-risk profile for atezolizumab in PD-L1 expressing NSCLC and support its use as adjuvant treatment.

Reference

Felip E, et al. Atezolizumab (atezo) vs best supportive care (BSC) in stage II-IIIA NSCLC with high PD-L1 expression: sub-analysis from the pivotal phase III IMpower010 study. Presented at ELCC 2022; Abstract 80O.