EGFR–TKI

Question  Does treatment with nivolumab affect the incidence of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR–TKI)-induced interstitial pneumonitis (IP) in non–small cell lung cancer (NSCLC) patients?

Findings  In this observational study including 20 516 patients with non–small cell lung cancer, the adjusted odds ratio for EGFR–TKI-associated IP in cases with and without nivolumab was 5.09 and 1.22, respectively. The difference was statistically significant.

Meaning  Treatment with nivolumab was associated with increased EGFR–TKI-induced interstitial pneumonitis.

Importance  Nivolumab and epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non–small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents.

Objective  To determine whether nivolumab increases EGFR–TKI-associated interstitial pneumonitis (IP).

Design, Setting, and Participants  A database study of 20 516 participants with NSCLC in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, performed between April 2015 and March 2017.

Main Outcomes and Measures  We compared the incidence of EGFR–TKI-associated IP in patients receiving and not receiving nivolumab treatment.

Results  The mean (SD) age of participants treated with EGFR-TKI, with and without nivolumab, was 64.4 (15.5) and 68.9 (11.8) years, respectively, and the proportion of men was 40.0% and 53.8%, respectively. Of the 20 516 participants with NSCLC, 985 cases (4.80%; 95% CI, 4.51-5.10) developed IP. Of 5777 patients treated with EGFR-TKI, 265 developed IP (4.59%; 95% CI, 4.06-5.16). Of 70 patients treated with both EGFR-TKI and nivolumab, 18 developed IP (25.7%; 95% CI, 16.0-37.6). The adjusted odds ratio for an interaction between EGFR-TKI and nivolumab was 4.31 (95% CI, 2.37-7.86; P