Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study. (September 2018)

• Record Type: Journal Article
• Authors: Horn, Leora; Gettinger, Scott N.; Gordon, Michael S.; Herbst, Roy S.; Gandhi, Leena; Felip, Enriqueta; Sequist, Lecia V.; Spigel, David R.; Antonia, Scott J.; Balmanoukian, Ani; Cassier, Philippe A.; Liu, Bo; Kowanetz, Marcin; O'Hear, Carol; Fassò, Marcella; Grossman, William; Sandler, Alan; Soria, Jean-Charles
• Is Part Of: European journal of cancer. Volume 101(2018)
• Page Start: 201
• Page End: 209
• Publication Date: 2018-09
• Subjects: Atezolizumab -- Non-small-cell lung cancer -- PD-L1 -- Immune checkpoint inhibitor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.06.031
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Introduction: Atezolizumab, an anti-programmed death-ligand 1 (PD-L1) antibody, inhibits PD-L1:PD-1 and PD-L1:B7.1 interactions, restoring anticancer immunity. Here, we report final analyses from the non-small-cell lung cancer (NSCLC) cohort of the first atezolizumab phase I study. Methods: Patients with NSCLC received atezolizumab 1–20 mg/kg or 1200 mg intravenously every 3 weeks. Baseline PD-L1 expression on tumour cells (TCs) and tumour-infiltrating immune cells (ICs) was assessed (VENTANA SP142 immunohistochemistry assay). Exploratory subgroup analyses investigated responses by baseline PD-L1 expression and oncogenic mutational status. Results: Eighty-nine patients, 98% of whom had received previous systemic therapy, were evaluable for safety and antitumour activity. Atezolizumab was well tolerated, with grade III/IV treatment-related adverse events (TRAEs) observed in 10 patients (11%). All-grade TRAEs occurring in >10% of patients were fatigue, nausea and decreased appetite; grade III/IV TRAEs occurring in >2% of patients were fatigue, dyspnoea, hyponatremia and hypoxia. One patient died from treatment-unrelated pneumonia. Objective response rate (ORR) was 50% (95% confidence interval [CI], 28%–72%), 33% (20%–48%), 29% (18%–41%) and 11% (1%–35%) for the TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3 and TC0 and IC0 subgroups, respectively. All-patient ORR was 23% (95% CI, 14%–33%). Median duration of response was 16.4 months (range, 7.2–53.4+). One-, 2-, and 3-year survival rates were 63% (95% CI, 53%–73%), 37% (26%–47%) and 28% (18%–38%), respectively. Conclusions: Single-agent atezolizumab was well tolerated with long-term clinical benefits, including durable responses and survival, in pretreated NSCLC. Improved responses and survival rates were seen with increasing baseline PD-L1 expression. ClinicalTrials.gov identifier: NCT01375842 . Highlights: Five-year follow-up of patients with NSCLC receiving single-agent atezolizumab. Atezolizumab continued to be well tolerated with a favourable safety profile. Responses with atezolizumab were durable with sustained survival benefit. PD-L1 expression enriches for clinical benefit with atezolizumab. Patients with no-to-low PD-L1 tumour expression derive benefit with atezolizumab.