Panitumumab Monotherapy Compared with Cetuximab and Irinotecan Combination Therapy in Patients with Previously Treated KRAS Wild-Type Metastatic Colorectal Cancer

Abstract

Background: The survival benefit for single-agent anti–epidermal growth factor receptor (EGFR) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mCRC) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan. Methods: The study enrolled patients with KRAS wt mCRC previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab–irinotecan before April 1, 2011, at the BC Cancer Agency (BCCA). Patients were excluded if they had received anti-EGFR agents in earlier lines of therapy. Data were prospectively collected, except for performance status (PS), which was determined by chart review. Information about systemic therapy was extracted from the BCCA Pharmacy Database. Results: Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab–irinotecan. Compared with patients treated with cetuximab–irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ECOG) PS of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab–irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ECOG PS of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01). Conclusions: Single-agent panitumumab and cetuximab–irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mCRC.

Cetuximab plus irinotecan versus panitumumab in patients with refractory metastatic colorectal cancer in Ontario, Canada

“…Only one retrospective study compared EGFR‐directed antibody therapy (Pmab) alone or in combination with chemotherapy (Cmab + I). In this study of 178 patients in British Columbia, Canada, all of whom were KRAS exon 2 wild‐type, the median OS favored combination therapy over monotherapy (8.3 vs 7.7 months) but this difference was not statistically significant [HR 1.29 (95% CI 0.77–2.14), p = 0.34] . TTD was not assessed and statistical power was very limited, with only 37 patients receiving combination therapy .…”

“…In this study of 178 patients in British Columbia, Canada, all of whom were KRAS exon 2 wild‐type, the median OS favored combination therapy over monotherapy (8.3 vs 7.7 months) but this difference was not statistically significant [HR 1.29 (95% CI 0.77–2.14), p = 0.34] . TTD was not assessed and statistical power was very limited, with only 37 patients receiving combination therapy . With a much larger sample size ( n = 1081), our study was better powered to detect an OS difference between combination and EGFR monotherapy.…”

“…13 TTD was not assessed and statistical power was very limited, with only 37 patients receiving combination therapy. 13 With a much larger sample size (n 5 1081), our study was better powered to detect an OS difference between combination and EGFR monotherapy.…”

Clinical Guidelines for Diagnosis, Treatment and Monitoring Patients With Colorectal Cancer

“…-FOLFIRI +/-bevacizumab ili afl ibercept ili ramucirumab bez obzira na status KRAS-a/NRAS-a (IA) ili -irinotekan +/-bevacizumab ili -FOLFIRI + cetuksimab ili panitumumab ako nisu primijenjeni u prvoj liniji kod tumora s KRAS-om/ NRAS-om divljeg tipa (IIA) ili -irinotekan + cetuksimab ili panitumumab ako nisu primijenjeni u prvoj liniji kod tumora s KRAS-om/ NRAS-om divljeg tipa (IIA). [52][53][54][55][56][57] Primjena treće linije kemoimunoterapije/kemoterapije rezervirana je za bolesnike dobra općeg stanja (ECOG 0 -2) i ovisi o ordiniranoj prethodnoj kemoimunoterapiji/ kemoterapiji.…”

Prognostic and predictive role of EGFR pathway alterations in biliary cancer patients treated with chemotherapy and anti-EGFR

“…Different strategies aimed at inhibiting EGFR with small molecules (erlotinib and gefitinib) or with monoclonal antibodies (cetuximab and panitumumab) have been developed over the years in many cancer types [ 1 – 6 ]. Panitumumab (Vectibix, Amgen), a fully human antibody directed against EGFR, was initially approved in KRAS wild type (WT) metastatic colorectal cancer (mCRC) patients refractory to previous chemotherapy [ 7 , 8 ]. In biliary tract carcinoma (BTC), preclinical evidence of antitumor activity [ 9 ] and the lack of compelling therapies suggested that the combination of standard chemotherapy and EGFR inhibitors could be an attractive option to improve patient outcome [ 10 , 11 ].…”