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)

Lung Cancer. 2025 May:203:108543. doi: 10.1016/j.lungcan.2025.108543. Epub 2025 Apr 18.

Abstract

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.

Keywords: Atezolizumab; Carboplatin; Immune checkpoint inhibitor; Nab-paclitaxel; Nonsquamous non–small cell lung cancer; Renal impairment.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Aged, 80 and over
  • Albumins / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carboplatin / administration & dosage
  • Carboplatin / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / complications
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Female
  • Humans
  • Lung Neoplasms* / complications
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Renal Insufficiency* / complications
  • Treatment Outcome

Substances

  • Carboplatin
  • Paclitaxel
  • atezolizumab
  • 130-nm albumin-bound paclitaxel
  • Antibodies, Monoclonal, Humanized
  • Albumins