Open AccessA Phase II Study of FOLFOXIRI Plus Panitumumab Followed by Evaluation for Resection in Patients With Metastatic KRAS Wild‐Type Colorectal Cancer With Liver Metastases Only
Author(s) -
Bendell Johanna C.,
Zakari Ahmed,
Peyton James D.,
Boccia Ralph,
Moskowitz Mark,
Gian Victor,
Lipman Andrew,
Waterhouse David,
LoCicero Richard,
Earwood Chris,
Lane Cassie M.,
Meluch Anthony
Publication year - 2016
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2015-0439
Subject(s) - medicine , kras , oxaliplatin , irinotecan , panitumumab , colorectal cancer , response evaluation criteria in solid tumors , gastroenterology , oncology , regimen , clinical endpoint , folinic acid , phases of clinical research , surgery , cancer , chemotherapy , clinical trial
Lessons LearnedThis regimen is a viable option for patients with liver‐only metastatic colorectal cancer. Enrollment criteria for future studies should include testing for the newly identified KRAS mutations.Background. Patients with liver‐only metastatic colorectal cancer (mCRC) who are not candidates for potentially curative resection may become resectable with more aggressive chemotherapy regimens. In this nonrandomized trial, we evaluated folinic acid, 5‐fluorouracil (5‐FU), oxaliplatin, and irinotecan (FOLFOXIRI) plus the epidermal growth factor receptor inhibitor panitumumab as first‐line treatment for KRAS wild‐type mCRC with liver‐only metastasis. Methods. Patients received FOLFOXIRI (5‐FU, 3,200 mg/m 2 , 48‐hour continuous intravenous (i.v.) infusion; leucovorin, 200 mg/m 2 i.v.; irinotecan, 125 mg/m 2 ; oxaliplatin, 85 mg/m 2 i.v.) and panitumumab (6 mg/kg i.v.) on day 1 of 14‐day cycles. Patients were restaged and evaluated for surgery every four cycles. Planned enrollment was originally 49 patients. The primary endpoint was objective response rate. Results. Fifteen patients (median age: 55 years; 87% male) received a median 6 cycles of treatment (range: 1–33 cycles); 10 patients (67%) were surgical candidates at baseline. Twelve patients were evaluable for clinical response; 9 (60%) achieved partial response. Ten patients underwent surgery; all had complete resections and pathologic partial response. Treatment‐related grade 3 adverse events included diarrhea (33%) and rash (20%). Enrollment was halted because of emerging data on expanded KRAS/NRAS mutations beyond the region we initially examined, and the potential for negative interaction with oxaliplatin‐based therapy. Eight patients underwent expanded KRAS/NRAS analysis outside exon 2; no additional mutations were found. Conclusion. KRAS/NRAS mutations outside the region tested in this study were recently shown to be associated with inferior survival on similar treatment regimens. Therefore, this trial was stopped early. This regimen remains a viable option for patients with liver‐only mCRC in the KRAS/NRAS wild‐type population. Enrollment criteria on future studies should include testing for the newly identified mutations.