Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08

• Published in: British journal of cancer Vol. 123; no. 10; pp. 1490 - 1495
• Main Authors: Masuishi, Toshiki, Tsuji, Akihito, Kotaka, Masahito, Nakamura, Masato, Kochi, Mitsugu, Takagane, Akinori, Shimada, Ken, Denda, Tadamichi, Segawa, Yoshihiko, Tanioka, Hiroaki, Hara, Hiroki, Sagawa, Tamotsu, Watanabe, Takanori, Takahashi, Takao, Negoro, Yuji, Manaka, Dai, Fujita, Hideto, Suto, Takeshi, Takeuchi, Masahiro, Ichikawa, Wataru, Fujii, Masashi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.11.2020; Nature Publishing Group
• Subjects: 631/67/1059/602; 631/67/1504/1885; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cetuximab - administration & dosage; Cetuximab - adverse effects; Chemotherapy, Adjuvant; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Disease control; Drug Resistance; Epidemiology; Female; Humans; Immunotherapy; Irinotecan; Irinotecan - administration & dosage; Irinotecan - adverse effects; K-Ras protein; Male; Metastases; Metastasis; Middle Aged; Molecular Medicine; Monoclonal antibodies; Neoplasm Metastasis; Oncology; Patients; Proto-Oncogene Proteins p21(ras) - genetics; Salvage Therapy; Survival; Survival Analysis; Targeted cancer therapy; Treatment Outcome
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-01042-w

Background Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC). Methods This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses. Results Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4–60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group. Conclusions Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial. Clinical trial registration UMIN000010638