Phase II Study of Third-Line Panitumumab Rechallenge in Patients with Metastatic Wild-Type KRAS Colorectal Cancer Who Obtained Clinical Benefit from First-Line Panitumumab-Based Chemotherapy: JACCRO CC-09

Target Oncol. 2021 Nov;16(6):753-760. doi: 10.1007/s11523-021-00845-y. Epub 2021 Oct 31.

Abstract

Background: Regorafenib and trifluridine/tipiracil are standard third-line chemotherapies for colorectal cancer patients, but their efficacy is limited. Anti-epidermal growth factor receptor antibody rechallenge has been reported to be promising for patients who have obtained clinical benefit from first-line cetuximab-based chemotherapy. Moreover, panitumumab showed non-inferior efficacy to cetuximab.

Objective: This study assessed the efficacy and safety of third-line panitumumab rechallenge in patients with metastatic KRAS exon 2 wild-type metastatic colorectal cancer who obtained clinical benefit from first-line panitumumab-based chemotherapy.

Patients and methods: This was a prospective, multicenter, phase II trial conducted from October 2013 to August 2017. Major eligibility criteria included KRAS exon 2 wild-type and achievement of complete response, partial response, or continued stable disease for at least 6 months in first-line panitumumab-based therapy. Irinotecan plus panitumumab treatment was continued until disease progression or unacceptable toxicity was observed. The primary endpoint was the 3-month progression-free survival (PFS) rate.

Results: Twenty-five patients were enrolled in this study. Their median age was 66.5 years, and the 3-month PFS rate was 50.0% (95% confidence interval 30.0-70.0). The median PFS and overall survival were 3.1 months and 8.9 months, respectively. The response rate and disease control rate were 8.3% and 50.0%, respectively. Common grade 3/4 adverse events were acneiform rash (17%), hypomagnesemia (13%), and dry skin (13%). No treatment-related deaths occurred.

Conclusion: Irinotecan plus panitumumab rechallenge is a promising third-line treatment regimen in patients with metastatic wild-type KRAS colorectal cancer.

Clinical trial identification: UMIN000015916.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cetuximab / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Colonic Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Humans
  • Irinotecan / pharmacology
  • Irinotecan / therapeutic use
  • Multicenter Studies as Topic
  • Panitumumab / pharmacology
  • Panitumumab / therapeutic use
  • Prospective Studies
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • KRAS protein, human
  • Panitumumab
  • Irinotecan
  • Proto-Oncogene Proteins p21(ras)
  • Cetuximab

Associated data

  • UMIN-CTR/UMIN000015916