Adverse events associated with sequential immune checkpoint inhibitor and alectinib in patients with ALK-rearranged advanced non-small-cell lung cancer

Abstract

Background

ALK tyrosine kinase inhibitors (TKIs) are the standard first-line therapy for ALK-rearranged [ALK fusion-positive (ALK+)] advanced non-small-cell lung cancer (NSCLC). In real-world practice, patients may receive immune checkpoint inhibitors (ICIs) before initiating ALK TKIs. We aimed to assess the frequency of treatment-related adverse events (TRAEs) associated with this sequential approach.

Patients and methods

We retrospectively analyzed alectinib-associated TRAEs in patients with advanced ALK+ NSCLC who received alectinib as their first TKI, with or without prior ICI exposure.

Results

We identified 166 patients, of whom 12 had prior ICI exposure. From alectinib initiation, the 12-month cumulative incidence in patients with versus without prior ICI was as follows: all-grade pneumonitis, 25.0% versus 4.6%; transaminase elevation, 25.0% versus 14.4%; and rash, 43.3% versus 5.9%. Competing-risks regression detected a higher risk of all-grade pneumonitis [hazard ratio (HR) 5.2], all-grade rash (HR 7.8), and grade ≥3 rash (HR 8.9) in patients with versus without prior ICI. Alectinib required discontinuation or hospitalization for TRAEs in 25.0% and 16.7% of patients with prior ICI, respectively, compared with 7.8% and 3.2% of patients without prior ICI.

Conclusions

Alectinib after ICI was associated with higher risks of pneumonitis and rash, and numerically higher risk of grade ≥3 hepatotoxicity, leading to increased rates of alectinib interruption and steroid use. These findings underscore the importance of expedited genotyping to guide treatment selection and avoid unwarranted ICI exposure.