A final analysis of a phase 3 trial showed a sustained overall survival (OS) benefit with the combination of atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP), compared with bevacizumab-carboplatin-paclitaxel (BCP), in patients with chemotherapy-naive metastatic non-squamous non-small cell lung cancer (NSCLC).
The analysis, published in the Journal of Thoracic Oncology, also showed that atezolizumab-carboplatin-paclitaxel (ACP) provided a numerical, but not statistically significant, improvement in OS compared with BCP.
The randomized, phase 3 IMpower150 trial (ClinicalTrials.gov Identifier: NCT02366143) was designed to compare ABCP or ACP with BCP in patients with metastatic non-squamous NSCLC. The study enrolled 1202 patients (intention-to-treat [ITT] population) at 240 medical centers in 26 countries. The participants were randomly assigned to ABCP (400 patients), ACP (402 patients), or BCP (400 patients).
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PD-L1–positive tumors were identified in 213 (53%) patients in the ACP arm, 209 (52.3%) patients in the ABCP arm, and 195 (48.8%) patients in the BCP arm. The ITT-wild type (WT) population (no EGFR or ALK alterations) included 1047 patients.
The median follow-up was 39.8 months in the ABCP arm, 38.8 months in the ACP arm, and 40.0 months in the BCP arm, with a minimum follow-up duration of 32.4 months in the ITT-WT population.
In the ITT-WT population, the median OS was 19.0 months with ACP and 14.7 months with BCP (hazard ratio [HR], 0.84; 95% CI, 0.71-1.00). The median OS was 19.5 months in the ABCP arm compared with 14.7 months in the BCP arm (HR, 0.80; 95% CI, 0.67-0.95). The median PFS was 6.3 months in the ACP arm and 8.4 months in the ABCP arm compared with 6.8 months in the BCP arm.
Exploratory analyses based on PD-L1 subgroups showed longer median OS among ITT patients with PD-L1-high tumors in the ACP arm (median 26.3 months; HR, 0.76; 95% CI, 0.49-1.17) and the ABCP arm (median 30.0 months; HR, 0.70; 95% CI, 0.46-1.08) than in the BCP arm (median 15.0 months). Likewise, patients with PD-L1–positive tumors had longer median OS with ABCP and ACP compared with BCP.
Conversely, among patients with PD-L1-negative tumors in the ITT-WT population, the median OS was similar in the ACP arm (14.8 months) compared with the BCP arm (14.1 months; HR, 0.96; 95% CI, 0.76-1.22), and there was limited OS improvement in the ABCP arm (16.9 months) compared with the BCP arm (14.1 months; HR, 0.90; 95% CI, 0.71-1.14).
Grade 3 to 4 adverse events occurred in 172 (43.0%) patients in the ACP arm, 225 (57.3%) patients in the ABCP arm, and 193 (49.0%) patients in the BCP arm. Grade 5 adverse events were reported in 4 (1.0%) patients treated with ACP, 12 (3.1%) patients treated with ABCP, and 10 (2.5%) patients treated with BCP.
AEs led to discontinuation of treatment in 14.5% of the patients in the ACP arm, 41.2% of the patients in the ABCP arm, and 26.4% of the patients in the BCP arm
“Although ACP showed only a numerical improvement in OS compared with BCP, both atezolizumab-containing regimens indicated an OS benefit in PD-L1–positive populations,” the authors wrote. “This report confirms and extends earlier analyses supporting ABCP as an efficacious first-line treatment option in patients with metastatic nonsquamous NSCLC based on its strong OS benefit versus BCP, and which led to its regulatory approval and inclusion as a standard of care in National Comprehensive Network and European Society of Medical Oncology guidelines.”
Disclosure: This research was supported by F. Hoffmann-La Roche Ltd./Genentech, Inc., a member of the Roche Group. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Socinski MA, Nishio M, Jotte RM, et al. IMpower150 final overall survival analyses for atezolizumab plus bevacizumab and chemotherapy in first-line metastatic nonsquamous non-small cell lung cancer. J Thorac Oncol. Published July 23, 2021. doi:10.1016/j.jtho.2021.07.009
