First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: A phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours

Abstract Background Frail elderly patients with metastatic colorectal cancer (mCRC) are not candidates for chemotherapy. Monotherapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies may be an option for these patients with few systemic toxic effects. Patients and methods Single-arm, multicentre, phase II trial including patients ⩾70years with wild-type (WT) KRAS (exon 2) mCRC, Eastern Cooperative Oncology Group (ECOG) status⩽3, KPC (Kohne Prognostic Classification) – defined intermediate or high risk status, frailty and/or ineligibility for chemotherapy. Patients received panitumumab until progression or unacceptable toxicity. The primary end-point was progression free survival (PFS) rate at 6months. Results The study included 33 patients (intention-to-treat (ITT) population). Median age: 81years; sex: 66.7% male; high-risk KPC status: 45.4%. Median treatment duration was 14weeks and 6-month PFS rate was 36.4% (95% confidence interval (CI): 20.0–52.8). The objective response rate: 9.1% (95% CI: 0–18.9) (all partial responses), and there were 18 stable diseases (54.5%). Median PFS was 4.3months (95% CI: 2.8–6.4) and median overall survival (OS) was 7.1months (95% CI: 5.0–12.3). There were no deaths or grade 4–5 adverse events (AEs) related to panitumumab and the most common grade 3-related AE was rash acneiform (15.2%). A significant association between clinical response and RAS status was observed ( P =0.037). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS , N =15), 6-month PFS rate was 53.3% (95% CI: 30.1–75.2) and median PFS and OS were 7.9 and 12.3months, respectively. Conclusions Single-agent panitumumab is active and well tolerated and may be a therapeutic option for high-risk frail elderly patients with WT RAS tumours considered not candidates for chemotherapy (clinicaltrials.gov identifier NCT01126112).