An Open-label, Single-arm, Phase 2 Trial of Panitumumab Plus FOLFIRI as Second-line Therapy in Patients with Metastatic Colorectal Cancer

Abstract

This prospective analysis evaluated the effect of tumor KRAS status on efficacy of second-line panitumumab plus folinic acid/5-fluorouracil/irinotecan (FOLFIRI). This phase 2, open-label, single-arm study enrolled patients with unresectable, measurable metastatic colorectal cancer (mCRC) after failure of first-line treatment with oxaliplatin-based chemotherapy plus bevacizumab. Patients received panitumumab 6 mg/kg plus FOLFIRI every 2 weeks until disease progression or intolerability. Tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) were performed by the investigators every 8 weeks from weeks 8-32 and every 12 weeks thereafter. KRAS status was determined by real-time polymerase chain reaction (PCR) on DNA extracted from fixed tumor sections. Efficacy endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS). Safety endpoints included incidence of adverse events (AEs). Endpoints were evaluated by tumor KRAS status. Of 116 patients enrolled, 109 patients with known tumor KRAS status received treatment; 59% had wild-type KRAS, and 41% had mutant KRAS. Fifteen patients (23%) with wild-type KRAS and 7 patients (16%) with mutant KRAS had a complete or partial response to treatment. Median PFS was 26 weeks (95% CI, 19-33 weeks) and 19 weeks (95% CI, 12-25 weeks) in the wild-type KRAS and mutant KRAS strata, respectively. Median OS was 50 weeks (95% CI, 39-76 weeks) and 31 weeks (95% CI, 23-47 weeks) in wild-type KRAS and mutant KRAS strata, respectively. Skin-related toxicities (86% of all patients) and diarrhea (74%) were the most common AEs. Panitumumab plus FOLFIRI numerically improved objective response rate, PFS, and OS in favor of patients with wild-type KRAS tumors. The safety profile was consistent with panitumumab plus FOLFIRI trials in similar patient populations.