Adjuvant atezolizumab in Japanese patients with resected stage IB-IIIA non-small cell lung cancer (IMpower010)

Abstract

The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in patients with resected stage IB-IIIA non-small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)-IIIA NSCLC. Upon completing 1-4 cycles of adjuvant cisplatin-based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator-assessed disease-free survival, tested hierarchically first in patients with stage II-IIIA NSCLC whose tumors expressed programmed death-ligand 1 (PD-L1) on ≥1% of tumor cells, then in all randomized patients with stage II-IIIA NSCLC, and finally in the intention-to-treat (ITT) population (stage IB-IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all-randomized stage II-IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD-L1 tumor cells ≥1% stage II-IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease-free survival improvement with atezolizumab vs BSC was observed in the PD-L1 tumor cells ≥1% stage II-IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25-1.08), all-randomized stage II-IIIA (unstratified HR, 0.62; 95% CI, 0.35-1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34-1.10) populations. Atezolizumab-related grade 3/4 adverse events occurred in 16% of patients; no treatment-related grade 5 events occurred. Adjuvant atezolizumab showed disease-free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.

Keywords: Japanese; PD-L1 inhibitor; PD-L1 protein; atezolizumab; non-small cell lung cancer.

FIGURE 1

IMpower010 patient profile in the Japanese subpopulation. Screening, enrollment, and randomization of patients enrolled at Japanese sites of the global IMpower010 study. BSC, best supportive care; ITT, intention‐to‐treat; NSCLC, non‐small cell lung cancer; PD‐L1, programmed death‐ligand 1; TC, tumor cells

FIGURE 2

Disease‐free survival in the Japanese PD‐L1 TC ≥ 1% stage II–IIIA population. Kaplan–Meier estimates of disease‐free survival in the atezolizumab and best supportive care arms are shown for Japanese patients in the stage II–IIIA population whose tumors expressed PD‐L1 on ≥1% of tumor cells (TC). DFS, disease‐free survival; NR, not reached; NSCLC, non‐small cell lung cancer; PD‐L1, programmed death‐ligand 1; TC, tumor cells

FIGURE 3

Disease‐free survival in key patient subgroups of the Japanese PD‐L1 TC ≥1% stage II–IIIA population. Forest plots of disease‐free survival in patient subgroups of the Japanese stage II–IIIA population with PD‐L1 expression on ≥1% of TC. ALK, anaplastic lymphoma kinase; BSC, best supportive care; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; NR, not reached; OS, overall survival; PD‐L1, programmed death‐ligand 1; TC, tumor cells. ^aPer electronic case report form