IMpower133 update: First-line atezolizumab plus chemo continues to show OS benefit in ES-SCLC
At a median follow-up of 22.9 months, atezolizumab plus carboplatin and etoposide (CP/ET), given as a first-line treatment, continued to demonstrate an improvement in overall survival (OS) vs placebo plus CP/ET in patients with extensive-stage small-cell lung cancer (ES-SCLC), according to updated results of the IMpower133 trial presented at the American Association for cancer Research (AACR) 2020 Virtual Annual Meeting II.
Patients in the atezolizumab plus CP/ET arm achieved a median OS of 12.3 months vs 10.3 months in the placebo plus CP/ET arm (hazard ratio [HR], 0.76; 95 percent confidence interval [CI], 0.60 to 0.95; p=0.0154). At 18 months, the OS rate was 13 percent higher among patients on atezolizumab plus CP/ET than those receiving placebo plus CP/ET (34 percent vs 21 percent). [Horn L, et al, AACR 2020 Virtual Meeting II, abstract 9759]
“At a median follow-up of 13.9 months, results of the pivotal IMpower133 trial demonstrated a significant improvement in progression-free survival and OS, which led to atezolizumab plus CP/ET becoming the first PD-L1/PD-1 inhibitor–containing regimen to gain US and EU regulatory approvals as first-line treatment for ES-SCLC,” said presenter, Dr Leora Horn of Vanderbilt University Medical Center, Nashville, Tennessee, US. [N Engl J Med 2018;379:2220-2229; Ann Oncol 2020;31:310-317] “Present updated results further support first-line atezolizumab plus CP/ET for patients with untreated ES-SCLC in an all-comer population.”
The addition of atezolizumab to CP/ET led to a consistent OS benefit vs placebo plus CP/ET across a majority of subgroups. “An OS benefit was observed in both the blood-based tumour mutational burden [bTMB]-high and bTMB-low subgroups, using the prespecified cut-offs of bTMB 10 and bTMB 16,” noted the researchers.
Post-hoc exploratory analysis was conducted for OS by PD-L1 expression. Results showed an OS benefit with atezolizumab plus CP/ET across all PD-L1 subgroups vs the placebo plus CP/ET arm. “Therefore, bTMB and PD-L1 status are not predictive of outcomes and should not be used for patient selection for this regimen,” commented the researchers.
“PD-L1 analysis was based on a limited data set [34 percent of the intention-to-treat population], partially due to the poor quality of tissue sample collection methods that may have damaged tissue architecture and limited the immunohistochemistry analyses,” explained Horn. “Further studies are needed to evaluate potential biomarkers and their association with outcomes.”
Confirmed objective response rate was 60.2 percent (95 percent CI, 53.1 to 67.0) in the atezolizumab plus CP/ET arm vs 64.4 percent (95 percent CI, 57.3 to 71.0) in the placebo plus CP/ET arm, while median duration of response was 4.2 months (95 percent CI, 4.1 to 4.5) vs 3.9 months (95 percent CI, 3.1 to 4.2) (HR, 0.67; 95 percent CI, 0.51 to 0.88).
Patterns of progression in specific organs were generally similar between arms. The most common sites for new lesions (≥10 percent of patients) were the central nervous system, lung, lymph nodes, and liver. “No differences in the incidence of new brain metastases were observed between arms,” highlighted Horn.
Adverse events (AEs) were comparable with the safety results reported from the primary analysis. Immune-related AEs of any grade were observed in 41.4 percent of patients on atezolizumab plus CP/ET vs 24.5 percent of patients on placebo plus CT/ET. Grade 3/4 rash, hepatitis and colitis occurred in 2.0 percent, 1.5 percent and 1.0 percent of patients on atezolizumab plus CP/ET, respectively, vs no patients on placebo plus CP/ET.