Multicenter, single-arm, phase II study of the continuous use of panitumumab in combination with FOLFIRI after FOLFOX for RAS wild-type metastatic colorectal cancer: Exploratory sequential examination of acquired mutations in circulating cell-free DNA.

Abstract

This multicenter single-arm, phase II study evaluated the efficacy and safety of uninterrupted panitumumab usage combined with cytotoxic doublets for unresectable/metastatic colorectal cancer (mCRC). Additionally, clinical value of the RAS/BRAF mutation status in circulating cell-free DNA (ccfDNA) was evaluated; this evaluation was measured independently of the protocol treatment. Eligible patients with RAS wild-type mCRC who had received the first-line panitumumab plus FOLFOX treatment were recruited and administered continuous panitumumab combined with FOLFIRI. Progression-free survival (PFS) at 6 months was the primary endpoint, with threshold and expected values of 35% and 50%, respectively. In total, 54 patients were enrolled between October 2017 and October 2019. The crude 6-month PFS rate was 37.0%, with a 4.8-month median PFS. The response rate and disease control rate were 16.7% and 50.0%, respectively. Notably, of the 54 participants, 17 showed RAS/BRAF mutations until the end of the protocol treatment and of the 22 patients with progressive disease as their best response, 10 possessed RAS/BRAF mutations in their plasma ccfDNA at baseline. The median PFS significantly differed among patients harboring tumors with BRAF and RAS mutations and those with wild-type tumors. In conclusion, our study failed to show the expected efficacy of the continuous panitumumab use in the second-line treatment. Liquid biopsy discriminated the duration of PFS according to the mutation status. The effectiveness of continuous treatment with panitumumab should be evaluated in patients with RAS/BRAF wild-type mCRC determined by liquid biopsy at the start of the second-line treatment.

• Authors: Jun Watanabe, Hiromichi Maeda, Takeshi Nagasaka, Mitsuru Yokota, Keiji Hirata, Naoya Akazawa, Yoshinori Kagawa, Takeshi Yamada, Manabu Shiozawa, Takayuki Ando, Takeshi Kato, Hideyuki Mishima, Junichi Sakamoto, Koji Oba, Naoki Nagata
• Journal: International journal of cancer (Int J Cancer) Vol. 151 Issue 12 Pg. 2172-2181 (Dec 15 2022) ISSN: 1097-0215 [Electronic] United States
• PMID: 35723084 (Publication Type: Multicenter Study, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 UICC.

Chemical References

• Panitumumab
• Proto-Oncogene Proteins B-raf
• Leucovorin
• Camptothecin
• Fluorouracil
• Cell-Free Nucleic Acids

Topics

• Humans
• Panitumumab (therapeutic use)
• Proto-Oncogene Proteins B-raf (genetics)
• Leucovorin (adverse effects)
• Camptothecin (adverse effects)
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Fluorouracil (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Mutation
• Colonic Neoplasms (drug therapy)
• Rectal Neoplasms (drug therapy)
• Cell-Free Nucleic Acids