Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer.

Journal Article (Journal Article)

TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT02008383 Sponsor: Duke University Principal Investigator: John H. Strickler IRB Approved: Yes LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted. BACKGROUND: The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance. METHODS: In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab. RESULTS: Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3-7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5-14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib. CONCLUSION: The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.

Full Text

Duke Authors

Cited Authors

  • Strickler, JH; Rushing, CN; Uronis, HE; Morse, MA; Niedzwiecki, D; Blobe, GC; Moyer, AN; Bolch, E; Webb, R; Haley, S; Hatch, AJ; Altomare, IP; Sherrill, GB; Chang, DZ; Wells, JL; Hsu, SD; Jia, J; Zafar, SY; Nixon, AB; Hurwitz, HI

Published Date

  • January 19, 2021

Published In

PubMed ID

  • 33469991

Pubmed Central ID

  • 33469991

Electronic International Standard Serial Number (EISSN)

  • 1549-490X

Digital Object Identifier (DOI)

  • 10.1002/onco.13678

Language

  • eng

Conference Location

  • United States