Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study

Abstract

Background: Pirfenidone is an antifibrotic agent that is potentially effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, no study has reported on its prophylactic value against chemotherapy-associated acute IPF exacerbations when combined with chemotherapy for non-small cell lung cancer (NSCLC). The present study assessed the safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy or immune checkpoint inhibitors (ICIs) in patients with IPF and NSCLC.

Methods: A total of 14 patients with IPF and NSCLC who received treatment from 2013 to 2019 were included. Patients were treated with pirfenidone combined with carboplatin and nanoparticle albumin-bound paclitaxel or S-1 as first-line chemotherapy. After confirming disease progression, patients received cytotoxic agents or ICIs, including nivolumab and pembrolizumab. Pirfenidone was continued regardless of chemotherapy changes. Overall survival (OS) and progression-free survival (PFS) for lung cancer and IPF were calculated. Moreover, the cumulative incidence of acute exacerbation of IPF (AE-IPF) within one year was evaluated.

Results: Median PFS for lung cancer was 110 days (95% confidence interval [CI]: 57-199 days), while the median OS was 362 days (95% CI: 220-526 days). Moreover, PFS for IPF was 447 days (95% CI: 286-indeterminate days), and the cumulative incidence of AE-IPF within one year was 18%. Notably, none of the patients developed AE-IPF associated with first-line chemotherapy. Among the included patients, four received ICIs, none of whom developed ICI-associated AE-IPF.

Conclusions: The present study found that pirfenidone combined with carboplatin-based regimens or ICIs might be safe first-line chemotherapy for patients with IPF and NSCLC.

Key points: SIGNIFICANT FINDINGS OF THE STUDY: No patients with IPF and NSCLC who received pirfenidone in combination with first-line carboplatin-based chemotherapy or late-line ICIs developed acute IPF exacerbations. What this study adds Pirfenidone might have a prophylactic effect against chemotherapy-associated AE-IPF.

Keywords: Acute exacerbation; immune checkpoint inhibitors; interstitial pneumonia; platinum-based chemotherapy; toxicity.

Figure 1

Patient inclusion flowchart. IP, interstitial pneumonia; IPF, idiopathic pulmonary fibrosis; NHO, National Hospital Organization; SCLC, small cell lung cancer.

Figure 2

Progression‐free survival (PFS) for lung cancer and overall survival (OS) in patients with idiopathic pulmonary fibrosis and non‐small cell lung cancer (n = 14). (a) Kaplan–Meier curve of PFS for lung cancer. Median PFS for lung cancer was 110 days (95% confidence interval [CI]: 57–199 days). (b) Kaplan–Meier curve of OS. Median OS was 362 days (95% CI: 220–526 days).

Figure 3

Progression‐free survival (PFS) for idiopathic pulmonary fibrosis (IPF) and cumulative incidence of acute exacerbation of IPF (AE‐IPF) (n = 14). (a) Kaplan–Meier curve of PFS for IPF. PFS for IPF was 447 days (95% CI: 286–indeterminate days). (b) Cumulative incidence of AE‐IPF within one year from the initiation of first‐line chemotherapy and throughout the entire period were 18% and 45%, respectively.