Real-world Evaluation of Second Line Chemotherapy for Patients With Advanced Non-small Cell Lung Cancer Harboring Preexisting Interstitial Lung Disease

Background: The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD.Methods: The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed.Results: Twenty-four patients with a median age of 71 years who were treated between April 2013 and March 2021 were included. The response rate after second-line chemotherapy with S-1 (n=13), docetaxel (n=8), pemetrexed (n=2), or docetaxel plus ramucirumab (n=1) was 12.5%, with a median progression-free survival (2nd line PFS) of 3.8 months. The overall survival from a start of first-line chemotherapy (1st line OS) and post-progression survival (PPS) post-first-line chemotherapy were 18.7 and 9.7 months, respectively. Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with 1st line OS (R = 0.85, P < 0.00001). Importantly, the 2nd line PFS was also significantly correlated with 1st line OS (R = 0.71, P = 0.0001). While second-line chemotherapy-related acute exacerbation of ILD was observed in 7 patients (29.2%), there were no treatment-related fatalities.Conclusions: Second-line chemotherapy has a strong positive impact on the OS of patients with NSCLC who have preexisting ILD. Given the findings of this study, second-line chemotherapy may be valuable in terms of prolonging long-term OS.