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. 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.

• Authors: Brian I Rini, Michael B Atkins, Toni K Choueiri, Despina Thomaidou, Brad Rosbrook, Maghull Thakur, Thomas E Hutson
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 19 Issue 5 Pg. e306-e312 (10 2021) ISSN: 1938-0682 [Electronic] United States
• PMID: 33947608 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Pfizer. Published by Elsevier Inc. All rights reserved.

Chemical References

• Protein Kinase Inhibitors
• Axitinib

Topics

• Axitinib (adverse effects)
• Carcinoma, Renal Cell (drug therapy)
• Hand-Foot Syndrome (etiology)
• Humans
• Kidney Neoplasms (drug therapy)
• Protein Kinase Inhibitors (adverse effects)