Time to resolution of axitinib-related adverse events after treatment interruption in patients with advanced renal cell carcinoma

Abstract Introduction Combined axitinib and immuno-oncology (IO) therapy is approved for first-line advanced renal cell carcinoma (aRCC). Overlapping toxicities represent a clinical challenge. Calculating the time to resolution (TTR) of common axitinib-related adverse events (AEs) following treatment interruption may help to identify AE etiology and determine appropriate management strategies. Materials and Methods Data from 5 randomized or single arm axitinib monotherapy or combination studies were analyzed. Patients with histologically confirmed clear cell aRCC were pooled into 3 cohorts based on treatment received: axitinib monotherapy, axitinib + IO, and other tyrosine kinase inhibitor (TKI). Any grade and grade ≥3 treatment-emergent diarrhea, fatigue, hypertension, nausea, and palmar-plantar erythrodysesthesia syndrome (PPE) were assessed. TTR was defined as the time from treatment interruption/discontinuation to resolution. Results The axitinib monotherapy cohort comprised 532 patients, the axitinib + IO cohort 541 patients, and the other TKI cohort 882 patients. Median TTR for all AEs (any grade) in the axitinib monotherapy cohort ranged from 1–3 days, except for fatigue (8 days). For diarrhea, hypertension, nausea, and PPE, median TTRs were longer in the axitinib + IO (4–11 days) and other TKI (7–8 days) cohorts versus the monotherapy cohort. Results were similar when only AEs of grade ≥3 were considered. Conclusions The TTR of monotherapeutic axitinib-related AEs is ≤3 days, except for fatigue, and generally numerically shorter than for other single agent TKIs and axitinib + IO. This has important implications for identifying AE etiology with combined axitinib-IO therapy and implementation of appropriate management strategies. ClinicalTrials.org identifiers: NCT00678392, NCT00920816, NCT02493751, NCT02684006, NCT02853331. MicroAbstract Overlapping toxicities are a concern with combined tyrosine kinase inhibitor (TKI) and immuno-oncology (IO) therapy for advanced renal cell carcinoma. We analyzed the resolution time of common axitinib-related adverse events (AEs) following treatment interruption due to the AE. Resolution time of AEs for axitinib monotherapy was typically ≤3 days and was numerically shorter versus other single agent TKIs. This can support identification of the etiology of AEs with combined TKI-IO therapy and may enable faster implementation of an appropriate management plan.