Oncology Advances: Adjuvant Atezolizumab Improves Survival Outcomes for Non-Small Cell Lung Cancer Regardless of Disease Stage, Regional Lymph Node Status

According to the 5-year follow-up data from the IMpower010 trial, atezolizumab continued to provide greater improvement to disease-free survival (DFS) and overall survival (OS) than best supportive care for patients with stage II to IIIA non-small cell lung cancer (NSCLC), and these improvements were seen regardless of disease stage or regional lymph node status.

The randomized, multicenter, open-label, phase 3 IMpower010 study enrolled 1280 patients with completely resected stage IB to IIIA NSCLC, between October 2015 and September 2018. After receiving adjuvant platinum-based chemotherapy for 1 to 4 cycles, patients were randomized on a 1-to-1 basis to receive either 1200mg adjuvant atezolizumab every 21 days for 16 cycles or 1 year (n = 507), or best supportive care, consisting of observation and regular scans for disease recurrence (n = 498). In each arm, 495 patients received treatment. The primary end point of IMpower010 was investigator-assessed DFS and was tested first among patients in the stage II-IIIA population subgroup with a PD-L1 ≥ 1%, then among all patients in the stage II-IIA population, and finally among the intention-to-treat population.

IMpower010 met its primary end point, with a DFS benefit seen among patients who received atezolizumab in the subgroup of patients with stage II-IIIA NSCLC and a “pronounced benefit” seen in the PD-L1 ≥ 1% subgroup. These was also an “enhanced benefit” seen among patients with PD-L1 ≥ 50%. There were no new safety signals at the initial reporting.

In this 5-year follow-up update (data cutoff date January 16, 2024), study authors report on outcomes by disease and regional lymph node status. Also included are descriptive analyses of sites of relapse and post-relapse treatments. Among patients with PD-L1 ≥ 1%, the DFS unstratified hazard ratio was the following for subgroups: stage II disease, 0.77; stage IIIA disease, 0.66; regional lymph node status N0, 0.82; regional lymph node status N1, 0.65; regional lymph node status N2, 0.74. For patients with PD-L1 ≥ 50%, the DFS unstratified HR was the following for subgroups: stage II, 0.57; stage IIIA, 0.42; regional lymph node status N0, 0.89; regional lymph node status N1, 0.40; regional lymph node status N2, 0.42. These patterns of improvement were similar for OS, and for DFS and OS when patients with EGFR or ALK alterations were excluded from the PD-L1 ≥ 50% population.

Among patients who relapsed after receiving atezolizumab, there were 43 locoregional only relapses, 33 distant only relapses, 9 central nervous system (CNS) only relapses, 12 locoregional and distant relapses, and 2 second primary lung only relapses in the PD-L1 ≥ 1% group. In the PD-L1 ≥ 50% group, there were 18 locoregional only relapses, 9 distant only, 2 CNS only, 4 locoregional and distant, and 1 second primary lung only. Among patients who relapses after receiving best supportive care, there were 48 locoregional only relapses, 45 distant only relapses, 12 central nervous system (CNS) only relapses, 18 locoregional and distant relapses, and 3 second primary lung only relapses in the PD-L1 ≥ 1% group. In the PD-L1 ≥ 50% group, there were 19 locoregional only relapses, 23 distant only, 7 CNS only, 8 locoregional and distant, and 3 second primary lung only.

Lead author Enriqueta Felip, MD, Vall d'Hebron University Hospital, Barcelona, Spain, and coauthors concluded, after over 5 years of follow-up, “patients in the atezolizumab arm had greater DFS and OS improvements than those in the [best supportive care] arm, regardless of disease stage or [regional lymph node] status, favoring N1/N2.” They went on to add that “overall recurrence rates were lower in the atezolizumab arm” regardless of PD-L1 ≥ 1% or PD-L1 ≥ 50% status, and that while the numbers were small, the distant and central nervous system relapse rates were higher in the best supportive care than in the atezolizumab arm for patients with PD-L1 ≥ 50%.

Source:

Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): A randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-1357. doi:10.1016/S0140-6736(21)02098-5.

Felip E, Wakelee HA, Vallieres E, et al. IMpower010 5-y subgroup analysis and relapse patterns: Phase 3 study of atezolizumab vs BSC in stage II-IIIA NSCLC. Presented at 2024 IASLC WCLC; September 7-10, 2024. San Diego, California.