Time to Resolution of Axitinib-Related Adverse Events After Treatment Interruption in Patients With Advanced Renal Cell Carcinoma
Brian I. Rini, Michael B. Atkins, Toni K. Choueiri, Despina Thomaidou, Brad Rosbrook, M. Thakur, Thomas E. Hutson
Abstract
INTRODUCTION: Combined axitinib and immuno-oncology (IO) therapy is approved for first-line advanced renal cell carcinoma. Overlapping toxicities represent a clinical challenge. Calculating the time to resolution (TTR) of common axitinib-related adverse events (AEs) after 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 advanced renal cell carcinoma 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 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 to 3 days, except for fatigue (8 days). For diarrhea, hypertension, nausea, and palmar-plantar erythrodysesthesia syndrome, 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 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.