Different incidence of interstitial lung disease according to different kinds of EGFR‐tyrosine kinase inhibitors administered immediately before and/or after anti‐PD‐1 antibodies in lung cancer

Abstract

Background The aim of our study was to retrospectively assess the incidence of interstitial lung disease (ILD) related to EGFR‐tyrosine kinase inhibitor (TKI) treatment immediately before and/or after the administration of a PD‐1 antibody. Methods We analyzed the data of 26 patients who underwent treatment with EGFR‐TKIs immediately before and/or after the administration of an anti‐PD‐1 antibody. Results Four out of the 26 patients developed ILD during EGFR‐TKI treatment: three patients during the administration of osimertinib immediately after, and one during afatinib immediately before treatment with an anti‐PD‐1 antibody. Three of 12 patients who underwent EGFR‐TKI therapy immediately after anti‐PD‐1 antibody treatment experienced osimertinib‐induced ILD. ILD was not observed in the five patients administered an anti‐PD‐1 antibody followed by first or second‐generation EGFR‐TKIs. Conclusion ILD was observed in the treatment sequence of an anti‐PD‐1 antibody followed by osimertinib, but not with first or second‐generation EGFR‐TKIs.

Osimertinib, a third‐generation EGFR tyrosine kinase inhibitor: A retrospective multicenter study of its real‐world efficacy and safety in advanced/recurrent non‐small cell lung carcinoma

“…Previous first‐generation EGFR‐TKI studies suggest that pulmonary injury in Japanese patients is associated with smoking history, poor PS, preexisting pulmonary fibrosis, and prior treatment with chemotherapy . Moreover, recent reports have described an increased incidence of interstitial lung disease in patients treated with osimertinib after treatment with anti‐PD‐1 antibody . In this study, neither did any patient have interstitial lung disease as the underlying disease nor did the one patient who received anti‐PD‐1 antibody prior to osimertinib have pneumonitis.…”

Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non‐small cell lung cancer harboring EGFR mutation

“…As there was a significant difference in the incidence of grade 3 or 4 hepatotoxicity between the DSG and non‐DSG groups, the frequency of this toxicity may differ according to the period from the last administration of nivolumab to the initiation of osimertinib. Generally, the administration of osimertinib as a third generation EGFR‐TKI immediately after ICI treatment is not permitted because of a high incidence of ILD; however, as the first‐ or second‐generation EGFR‐TKI immediately after ICI is described to be feasible without increased frequency of ILD . First generation, especially erlotinib or second‐generation EGFR‐TKI, can be administered without severe hepatotoxicity, even immediately after ICI treatment.…”

“…Generally, the administration of osimertinib as a third generation EGFR-TKI immediately after ICI treatment is not permitted because of a high incidence of ILD; however, as the firstor second-generation EGFR-TKI immediately after ICI is described to be feasible without increased frequency of ILD. 5 First generation, especially erlotinib or secondgeneration EGFR-TKI, can be administered without severe hepatotoxicity, even immediately after ICI treatment.…”

“…Although only 34 patients were treated with this combination therapy in their study, ILD was observed in 38% of all patients and 60% of Japanese patients . Moreover, a recent study described an increased incidence of ILD in patients who received osimertinib immediately after nivolumab, an anti‐PD‐1 antibody …”

“…3 Moreover, a recent study described an increased incidence of ILD in patients who received osimertinib immediately after nivolumab, an anti-PD-1 antibody. 4,5 Generally, hepatotoxicity is a major adverse event (AE) of anticancer drugs. However, little is known about the incidence of hepatotoxicity accompanying osimertinib administration immediately after ICI treatment.…”