In the phase III IMpower010 trial reported in The Lancet, Enriqueta Felip, MD, and colleagues found that the use of adjuvant atezolizumab after adjuvant platinum-based chemotherapy significantly improved disease-free survival vs best supportive care in patients with resected stage II to IIIA non–small cell lung cancer (NSCLC), with the benefit most marked among those with tumor cell PD-L1 expression ≥ 1%. Improvement in the entire population of patients with stage IB to IIIA disease did not reach significance in hierarchical testing.
Enriqueta Felip, MD
In the open-label trial, 1,005 patients with stage IB to IIIA disease from sites in 22 countries who had undergone complete resection and received one to four cycles of adjuvant platinum-based chemotherapy were randomly assigned between October 2015 and September 2018 to receive atezolizumab at 1,200 mg every 21 days for 16 cycles or 1 year (n = 507) or best supportive care (n = 498). The primary endpoint of investigator-assessed disease-free survival was tested hierarchically in the stage II to IIIA population with tumor cell PD-L1 expression ≥ 1% (n = 248 in atezolizumab group; n = 228 in control group), in all patients in the stage II to IIIA population (n = 442; n = 440), and in the intention-to-treat (ITT) population (all stage IB–IIIA).
Median follow-up was 32 to 33 months among all populations tested. In the stage II to IIIA population with tumor cell PD-L1 expression ≥ 1%, median disease-free survival was not reached (95% confidence interval [CI] = 36.1 months–not evaluable) in the atezolizumab group vs 35.3 months (95% CI = 29.0 months–not evaluable) in the control group (hazard ratio [HR] = 0.66, 95% CI = 0.50–0.88, P = .0039). In the stage II to IIIA population, median disease-free survival was 42.3 months (95% CI = 36.0 months–not evaluable) in the atezolizumab group vs 35.3 months (95% CI = 30.4–46.4 months) in the control group (HR = 0.79, 95% CI = 0.64–0.96, P = .020). In the ITT population, median disease-free survival was not reached (95% CI = 36.1 months–not evaluable) in the atezolizumab group vs 37.2 months (95% CI = 31.6 months–not evaluable) in the control group (HR = 0.81, 95% CI = 0.67–0.99, P = .040), with the prespecified boundary for statistical significance in the ITT analysis not being met.
Overall survival was not formally tested due to the absence of statistical significance in the ITT disease-free survival analysis. In the ITT population, death had occurred in 19% of the atezolizumab group vs 18% of the control group at time of analysis. Hazard ratios were 1.07 (95% CI = 0.80–1.42) in the ITT population, 0.99 (95% CI = 0.73–1.33) in the stage II to IIIA population, and 0.77 (95% CI = 0.51–1.17) in the stage II to IIIA population with PD-L1 ≥ 1%.
Grade 3 or 4 adverse events occurred in 22% of patients in the atezolizumab group vs 12% of the control group; the most common in the atezolizumab group were increased alanine aminotransferase (2%), pneumonia (1%), and increased aspartate aminotransferase (1%). Serious adverse events occurred in 18% vs 8% of patients.
Adverse events led to discontinuation of atezolizumab in 18% of patients, most commonly due to pneumonitis, hypothyroidism, and increased aspartate aminotransferase (1% each). Treatment-related death occurred in four patients in the atezolizumab group, due to myocarditis, interstitial lung disease, multiple organ dysfunction syndrome, and acute myeloid leukemia, respectively.
The investigators concluded, “IMpower010 showed a disease-free survival benefit with atezolizumab vs best supportive care after adjuvant chemotherapy in patients with resected stage II to IIIA NSCLC, with pronounced benefit in the subgroup whose tumors expressed PD-L1 on 1% or more of tumor cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC.”
Dr. Felip, of Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, is the corresponding author for The Lancet article.
Disclosure: The study was funded by F. Hoffmann-La Roche and Genentech. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.