Phase II study of carboplatin/nab-paclitaxel/atezolizumab combination therapy for advanced nonsquamous non-small cell lung cancer patients with impaired renal function: RESTART trial

BMC Cancer. 2022 Sep 8;22(1):964. doi: 10.1186/s12885-022-10056-x.

Abstract

Background: First-line treatment of nonsquamous non-small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with immune checkpoint inhibitors (ICIs). However, phase III studies of combinations of cytotoxic chemotherapy and ICIs have included only patients with maintained organ function, not those with renal impairment.

Methods: Cytotoxic chemotherapy-naïve advanced nonsquamous NSCLC patients aged 20 years or older with impaired renal function (creatinine clearance of 15 to 45 mL/min) are prospectively registered in this single-arm phase II study and receive combination therapy with carboplatin, nanoparticle albumin-bound (nab-) paclitaxel, and atezolizumab. Individuals with known genetic driver alterations including those affecting EGFR, ALK, ROS1, BRAF, MET, RET, and NTRK are excluded. We plan to enroll 40 patients over 2 years at 32 oncology facilities in Japan. The primary end point is confirmed objective response rate.

Discussion: If the study demonstrates efficacy and safety of carboplatin/nab-paclitaxel/atezolizumab, then this combination regimen may become a treatment option even for nonsquamous NSCLC patients with impaired renal function.

Trial registration: Registered with Japan Registry for Clinical Trials on 25 February 2021 (jRCTs071200102).

Keywords: Chemotherapy; Clinical trial; Immune checkpoint inhibitor; Nonsquamous non–small cell lung cancer; Renal impairment.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Albumins
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carboplatin
  • Carcinoma, Non-Small-Cell Lung* / complications
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Humans
  • Kidney / physiology
  • Lung Neoplasms* / chemically induced
  • Lung Neoplasms* / complications
  • Lung Neoplasms* / drug therapy
  • Paclitaxel
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Renal Insufficiency* / chemically induced

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antibodies, Monoclonal, Humanized
  • Proto-Oncogene Proteins
  • atezolizumab
  • Carboplatin
  • Protein-Tyrosine Kinases
  • Paclitaxel