Gemcitabine plus nab‐paclitaxel for pancreatic cancer and interstitial lung disease: A nationwide longitudinal study

Interstitial lung disease (ILD) is an adverse event associated with gemcitabine administration. Gemcitabine plus nab‐paclitaxel, which is now a first‐line chemotherapy regimen for pancreatic cancer (PC), may increase the risk of ILD; however, large‐scale clinical data on this are limited. Thus, this study aimed to elucidate the incidence and risk factors of ILD in patients with PC receiving gemcitabine plus nab‐paclitaxel. Through the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database with outpatient data, we identified consecutive patients with PC who received gemcitabine‐based chemotherapy between July 2010 and March 2019 at 205 hospitals. Competing‐risk analysis was used to examine the cumulative incidence and risk factors of ILD. Among the 6163 patients who received gemcitabine plus nab‐paclitaxel, we documented 168 patients (2.7%) who developed ILD with cumulative incidence rates (95% confidence intervals [CIs]) of 2.0% (1.6%–2.4%), 2.7% (2.2%–3.1%), and 3.1% (2.6%–3.6%) at 3, 6, and 12 months, respectively. Compared with patients with PC who received gemcitabine monotherapy, those who received gemcitabine plus nab‐paclitaxel had an adjusted subdistribution hazard ratio (SHR) for ILD of 1.93 (95% CI: 1.51–2.47). Older age was associated with a high risk of ILD in patients receiving gemcitabine plus nab‐paclitaxel (adjusted SHR comparing ≥75 to ≤74 years, 1.61; 95% CI: 1.16–2.24). In conclusion, this study demonstrated the clinical course of gemcitabine plus nab‐paclitaxel‐associated ILD in patients with PC. When gemcitabine plus nab‐paclitaxel is administered to elderly patients with PC, symptoms associated with ILD must be monitored.