Rechallenge chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel for patients with non-small cell lung cancer and interstitial lung disease: A multicenter retrospective study

• There is no standard second-line treatment for NSCLC patients with comorbid ILD. • Rechallenge with carboplatin plus paclitaxel or nab-paclitaxel led to an ORR of 27%. • This rechallenge regimen was associated with acute ILD exacerbation in 7% of cases. • A prospective study is currently ongoing to evaluate this rechallenge strategy. In patients with non-small cell lung cancer (NSCLC) and comorbid interstitial lung disease (ILD), carboplatin plus paclitaxel or nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has demonstrated efficacy and safety as a first-line treatment in clinical trials. However, no standard second-line treatment has been established. This multicenter retrospective study examined the efficacy and safety of rechallenge chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel in patients with NSCLC and ILD. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Threshold and expected ORRs were set at 8.3% and 27.5%, respectively. A one-sided type I error of 5% and power of 80% were assumed, warranting a sample size of 24 patients. Thirty patients who received carboplatin plus paclitaxel or nab-paclitaxel rechallenge chemotherapy between January 2018 and December 2022 were enrolled in this study. The median follow-up duration was 8.2 months (range: 1.6–54.3 months). The ORR was 27% (90% confidence interval CI: 14–43%; 95% CI: 12–46%), exceeding the pre-specified threshold. Median PFS and OS were 3.2 months (95% CI: 2.3–3.9 months) and 9.8 months (95% CI: 6.7–14.4 months), respectively. Acute exacerbation of ILD occurred in two patients (7%), both of whom had been receiving corticosteroid therapy for ILD, and resulted in death in one patient (3%). Rechallenge chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel could be an effective and safe option for patients with pretreated NSCLC with comorbid ILD.