Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial

Eur Respir J. 2022 Dec 15;60(6):2200380. doi: 10.1183/13993003.00380-2022. Print 2022 Dec.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF.

Methods: Chemotherapy-naïve advanced NSCLC patients with IPF were allocated to receive carboplatin (area under the curve of 6 on day 1) plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (100 mg·m-2 on days 1, 8 and 15) every 3 weeks with or without nintedanib (150 mg twice daily, daily). The primary end-point was exacerbation-free survival (EFS).

Results: Between May 2017 and February 2020, 243 patients were enrolled. Median EFS was 14.6 months in the nintedanib plus chemotherapy group and 11.8 months in the chemotherapy group (hazard ratio (HR) 0.89, 90% CI 0.67-1.17; p=0.24), whereas median progression-free survival was 6.2 and 5.5 months, respectively (HR 0.68, 95% CI 0.50-0.92). Overall survival was improved by nintedanib in patients with nonsquamous histology (HR 0.61, 95% CI 0.40-0.93) and in those at GAP (gender-age-physiology) stage I (HR 0.61, 95% CI 0.38-0.98). Seven (2.9%) out of 240 patients experienced acute exacerbation during study treatment.

Conclusions: The primary end-point of the study was not met. However, carboplatin plus nab-paclitaxel was found to be effective and tolerable in advanced NSCLC patients with IPF. Moreover, nintedanib in combination with such chemotherapy improved overall survival in patients with nonsquamous histology.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Carboplatin
  • Carcinoma, Non-Small-Cell Lung* / complications
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis* / complications
  • Idiopathic Pulmonary Fibrosis* / drug therapy
  • Lung Neoplasms* / complications
  • Lung Neoplasms* / drug therapy
  • Male
  • Paclitaxel

Substances

  • Carboplatin
  • nintedanib
  • Paclitaxel

Associated data

  • UMIN-CTR/UMIN000026799