Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC.

Abstract

BACKGROUND:

The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those of platinum-based chemotherapy, as first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC) with PD-L1 expression are not known.

METHODS:

We conducted a randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay. Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. Overall survival (primary end point) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with respect to EGFR mutations or ALK translocations. Within the population with EGFR and ALK wild-type tumors, overall survival and progression-free survival were also prospectively assessed in subgroups defined according to findings on two PD-L1 assays as well as by blood-based tumor mutational burden.

RESULTS:

Overall, 572 patients were enrolled. In the subgroup of patients with EGFR and ALK wild-type tumors who had the highest expression of PD-L1 (205 patients), the median overall survival was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P = 0.01). Among all the patients who could be evaluated for safety, adverse events occurred in 90.2% of the patients in the atezolizumab group and in 94.7% of those in the chemotherapy group; grade 3 or 4 adverse events occurred in 30.1% and 52.5% of the patients in the respective groups. Overall and progression-free survival favored atezolizumab in the subgroups with a high blood-based tumor mutational burden.

CONCLUSIONS:

Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type. (Funded by F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).

• Authors: Roy S Herbst, Giuseppe Giaccone, Filippo de Marinis, Niels Reinmuth, Alain Vergnenegre, Carlos H Barrios, Masahiro Morise, Enriqueta Felip, Zoran Andric, Sarayut Geater, Mustafa Özgüroğlu, Wei Zou, Alan Sandler, Ida Enquist, Kimberly Komatsubara, Yu Deng, Hiroshi Kuriki, Xiaohui Wen, Mark McCleland, Simonetta Mocci, Jacek Jassem, David R Spigel
• Journal: The New England journal of medicine (N Engl J Med) Vol. 383 Issue 14 Pg. 1328-1339 (10 01 2020) ISSN: 1533-4406 [Electronic] United States
• PMID: 32997907 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Massachusetts Medical Society.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• B7-H1 Antigen
• CD274 protein, human
• Deoxycytidine
• atezolizumab
• Carboplatin
• Cisplatin
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• B7-H1 Antigen (metabolism)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, metabolism, mortality)
• Carcinoma, Squamous Cell (drug therapy)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Humans
• Lung Neoplasms (drug therapy, genetics, metabolism, mortality)
• Male
• Middle Aged
• Mutation
• Survival Analysis
• Gemcitabine