Time to Resolution of Axitinib-Related Adverse Events After Treatment Interruption in Patients With Advanced Renal Cell Carcinoma

Overlapping toxicities are a concern with combined tyrosine kinase inhibitor (TKI)/immuno-oncology (IO) therapy for advanced renal cell carcinoma. We analyzed the resolution time of common adverse events (AEs). Resolution time for axitinib monotherapy was <= 3 days and shorter versus other single-agent TKIs. This can support identification of the etiology of AEs with combined TKI-IO therapy and faster management plan implementation. 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. (C) 2021 Pfizer. Published by Elsevier Inc.

Automated summary

The resolution time of common adverse events (AEs) in monotherapeutic axitinib treatment is typically <= 3 days, providing insights for identifying AE etiology and implementing appropriate management strategies in combined axitinib-IO therapy.