Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non–small-cell lung cancer

• Published in: European journal of cancer (1990) Vol. 101; pp. 114 - 122
• Main Authors: Liu, Stephen V., Camidge, D. Ross, Gettinger, Scott N., Giaccone, Giuseppe, Heist, Rebecca S., Hodi, F. Stephen, Ready, Neal E., Zhang, Wei, Wallin, Jeffrey, Funke, Roel, Waterkamp, Daniel, Foster, Paul, Iizuka, Koho, Powderly, John
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2018; Elsevier Science Ltd
• Subjects: Adult; Aged; Aged, 80 and over; Anemia; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Atezolizumab; B7 antigen; Cancer; Cancer therapies; Carboplatin; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Cell death; Chemotherapy; Chemotherapy–immunotherapy combinations; Confidence intervals; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunomodulation; Immunotherapy; Lung cancer; Lung Neoplasms - drug therapy; Male; Middle Aged; Monoclonal antibodies; Neutropenia; Neutropenia - chemically induced; Non-small cell lung carcinoma; Non–small-cell lung cancer; Paclitaxel; Patients; PD-L1 protein; Platinum; Proteins; Survival; Survival Analysis; Targeted cancer therapy; Time Factors; Treatment Outcome; Tumors; Non–small-cell lung cancer; Chemotherapy; Immunotherapy; Chemotherapy–immunotherapy combinations; Atezolizumab
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2018.06.033

Before the availability of immunotherapy, chemotherapy was standard first-line therapy for non–small-cell lung cancer (NSCLC) lacking actionable gene alterations. Preclinical evidence suggests chemotherapy is immunomodulatory, supporting chemotherapy/immunotherapy combinations. Atezolizumab, anti-programmed death ligand-1 (PD-L1) antibody, blocks programmed cell death protein-1 and B7.1 interaction with PD-L1. GP28328 (NCT01633970) assessed atezolizumab with chemotherapy in multiple tumours; we report results for advanced, treatment-naïve NSCLC. Patients received atezolizumab plus carboplatin with paclitaxel (Arm C: atezo/cb/pac), pemetrexed (Arm D: atezo/cb/pem, maintenance pemetrexed permitted), or nab-paclitaxel (Arm E: atezo/cb/nab-pac), four–six cycles, then atezolizumab maintenance. Primary end-point was safety; secondary end-points were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Seventy-six NSCLC patients were enrolled (n = 25, 25 and 26 for Arms C, D and E, respectively). Common treatment-related grade III/IV adverse events were neutropenia (36% atezo/cb/pac, 36% atezo/cb/pem, 42% atezo/cb/nab-pac) and anaemia (16% atezo/cb/pac, 16% atezo/cb/pem, 31% atezo/cb/nab-pac). Confirmed ORRs were 36% atezo/cb/pac, 68% atezo/cb/pem (one complete response [CR]) and 46% atezo/cb/nab-pac (four CRs). Median PFS was 7.1 months, (95% confidence interval [CI]: 4.2–8.3), 8.4 months (95% CI: 4.7–11) and 5.7 months (95% CI: 4.4–14.8), respectively. Median OS was 12.9 months (95% CI: 8.8–21.3), 18.9 months (95% CI: 9.9–27.4) and 17.0 months (95% CI: 12.7–not evaluable), respectively. Atezolizumab with chemotherapy was well tolerated with encouraging efficacy, though the analysis was limited by small numbers. NSCLC chemotherapy combination studies are ongoing. NCT01633970. •Atezolizumab in combination with platinum-doublet chemotherapy was well tolerated.•Median progression-free survival ranged from 5.7 to 8.4 months.•Overall survival ranged from 12.9 to 18.9 months.•Despite small numbers, efficacy supports further investigation.