The safety profile of EGFR/ALK-TKIs administered immediately before or after ICIs in advanced NSCLC

Background: As more therapeutic targets are being discovered in advanced non-small cell lung cancer (NSCLC), it is pivotal for clinicians to correctly sequence immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for delivery of safe and effective treatment. Our present study aimed to assess the safety profile of sequential treatment of TKIs and ICIs in advanced NSCLC.

Methods: We retrospectively analyzed the data of 64 patients who underwent sequential treatment of EGFR/ALK-TKIs and ICIs, including all the EGFR/ALK-TKIs and ICIs approved by National Medical Products Administration (NMPA) in China.

Results: The decrease in hemoglobin was the most common adverse event (54.5 % and 44.4 %) for all patients. For TKIs post-treatment with ICIs group, the incidence rate of decrease in white blood cells was 32.7 %. Liver toxicity was also common for this sequential therapy: treatment-related elevation in ALT (30.9 %) and AST (25.5 %). In addition, grade 3 or higher skin toxicity occurred in 2 patients, and grade 3 or higher neuritis was observed in 1 patient. Interstitial pneumonia was also observed in 1 patient. For patients within the group of TKIs pre-treatment with ICIs, the most common adverse event was hepatic toxicity, the elevation in ALT and AST was 33.3 % and 22.2 % respectively. It was worth noting that the incidence rate of grade 3 or higher elevation in ALT and AST was 22.2 %. Other adverse events such as blood toxicity, skin rash, and diarrhea were also observed in this sequential treatment, but most of which was slight.

Conclusion: Although the adverse event did not significantly increase in the sequential treatment pattern of our study, careful consideration should be given to the possibility of an increased risk of some adverse event when TKIs were pre/post-treated with ICIs.