Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial

• Published in: Journal of thoracic oncology Vol. 15; no. 8; pp. 1351 - 1360
• Main Authors: Jotte, Robert, Cappuzzo, Federico, Vynnychenko, Ihor, Stroyakovskiy, Daniil, Rodríguez-Abreu, Delvys, Hussein, Maen, Soo, Ross, Conter, Henry J., Kozuki, Toshiyuki, Huang, Kuan-Chieh, Graupner, Vilma, Sun, Shawn W., Hoang, Tien, Jessop, Helen, McCleland, Mark, Ballinger, Marcus, Sandler, Alan, Socinski, Mark A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2020; Copyright by the International Association for the Study of Lung Cancer
• Subjects: Albumins; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Atezolizumab; Carboplatin; Carcinoma, Squamous Cell - drug therapy; Humans; IMpower131; Lung Neoplasms - drug therapy; Nab-paclitaxel; Paclitaxel - therapeutic use; Squamous NSCLC; Carboplatin; IMpower131; Squamous NSCLC; Nab-paclitaxel; Atezolizumab
• ISSN: 1556-0864; 1556-1380; 1556-1380
• DOI: 10.1016/j.jtho.2020.03.028

Cytotoxic agents have immunomodulatory effects, providing a rationale for combining atezolizumab (anti-programmed death-ligand 1 [anti–PD-L1]) with chemotherapy. The randomized phase III IMpower131 study (NCT02367794) evaluated atezolizumab with platinum-based chemotherapy in stage IV squamous NSCLC. A total of 1021 patients were randomized 1:1:1 to receive atezolizumab+carboplatin+paclitaxel (A+CP) (n = 338), atezolizumab+carboplatin+nab-paclitaxel (A+CnP) (n = 343), or carboplatin+nab-paclitaxel (CnP) (n = 340) for four or six 21-day cycles; patients randomized to the A+CP or A+CnP arms received atezolizumab maintenance therapy until progressive disease or loss of clinical benefit. The coprimary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS) in the intention-to-treat (ITT) population. The secondary end points included PFS and OS in PD-L1 subgroups and safety. The primary PFS (January 22, 2018) and final OS (October 3, 2018) for A+CnP versus CnP are reported. PFS improvement with A+CnP versus CnP was seen in the ITT population (median, 6.3 versus 5.6 mo; hazard ratio [HR] = 0.71, 95% confidence interval [CI]: 0.60–0.85; p = 0.0001). Median OS in the ITT population was 14.2 and 13.5 months in the A+CnP and CnP arms (HR = 0.88, 95% CI: 0.73–1.05; p = 0.16), not reaching statistical significance. OS improvement with A+CnP versus CnP was observed in the PD-L1–high subgroup (HR = 0.48, 95% CI: 0.29–0.81), despite not being formally tested. Treatment-related grade 3 and 4 adverse events and serious adverse events occurred in 68.0% and 47.9% (A+CnP) and 57.5% and 28.7% (CnP) of patients, respectively. Adding atezolizumab to platinum-based chemotherapy significantly improved PFS in patients with first-line squamous NSCLC; OS was similar between the arms.