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

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSION:

Atezolizumab with chemotherapy was well tolerated with encouraging efficacy, though the analysis was limited by small numbers. NSCLC chemotherapy combination studies are ongoing. CLINICALTRIALS.

GOV IDENTIFIER:

NCT01633970.

• Authors: Stephen V Liu, D Ross Camidge, Scott N Gettinger, Giuseppe Giaccone, Rebecca S Heist, F Stephen Hodi, Neal E Ready, Wei Zhang, Jeffrey Wallin, Roel Funke, Daniel Waterkamp, Paul Foster, Koho Iizuka, John Powderly
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 101 Pg. 114-122 (09 2018) ISSN: 1879-0852 [Electronic] England
• PMID: 30053670 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• atezolizumab
• Carboplatin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Neutropenia (chemically induced)
• Survival Analysis
• Time Factors
• Treatment Outcome