Atezolizumab with carboplatin plus nab-paclitaxel combination therapy for advanced nonsquamous non-small cell lung cancer with impaired renal function: A multicenter, single-arm phase 2 trial (RESTART, LOGiK 2002)

Background: The current standard of care for advanced non–small cell lung cancer (NSCLC) without driver oncogenes is platinum-based chemotherapy together with immune checkpoint inhibition. However, most phase 3 trials of such combination therapy have excluded patients with renal impairment, with prospective data on its efficacy and safety in such patients thus being limited. Methods: This multicenter, single-arm phase 2 study enrolled chemotherapy-naïve individuals with advanced nonsquamous NSCLC and renal impairment defined as a creatinine clearance (CCr) of 15 to <45 mL/min. Patients received four cycles of atezolizumab in combination with carboplatin plus nab-paclitaxel, followed by atezolizumab alone. The primary endpoint of the study was objective response rate as determined by Response Evaluation Criteria in Solid Tumors. Results: Twenty-five patients were enrolled from 13 centers. The median age was 78 years (range, 63–83 years). Median CCr was 38.0 mL/min (range, 19.0–44.3 mL/min). There were no treatment-related deaths or cases requiring hemodialysis. Worsening of chronic kidney disease to grade 4, defined as a CCr of <15 mL min⁻¹ 1.73 m⁻², occurred in two patients (8 %), with the decreases in CCr being transient and both patients subsequently recovering. The objective response rate was 36.0 % (60 % confidence interval, 28.4–44.4 %), and the study did not meet its primary endpoint. Median progression-free survival and overall survival were 7.1 and 19.9 months, respectively. Conclusions: Carboplatin plus nab-paclitaxel with atezolizumab is a potentially feasible treatment option for advanced nonsquamous NSCLC with renal impairment.