Correlation of Kras Status with Cetuximab Activity in Heavily Treated Patients with Squamous Cell Anal Carcinoma
Authors: Graziela Dal Molin, Mariana Macedo, Maria Dirlei Begnami, Barbara Collares, Bruno Conte, Marcello Ferretti Fanelli, Aldo Dettino, Celso Mello
Journal: Annals of Oncology (2013)

Background: EGFR protein expression in SCAC is frequent and low rate of KRAS mutation has been described. As a result, Cetuximab would be a putative anti-EGFR agent for treatment of SCAC. No robust data are available about the efficacy of CET for this rare disease. The objective is to evaluate the activity of Cetuximab (CET) for metastatic squamous cell anal carcinoma (SCAC) in third line of treatment and correlate with KRAS mutation status.Methods: We retrospectively analyzed patients treated at our institution with CET. Variables such as age, gender, HIV infection, and treatment combination were evaluated. KRAS status was obtained by DNA pyrosequencing method of exon 1 on the primary tumor sample. We considered time to progression (TTP) as the main end-point for efficacy.Results: We identified 5 patients treated with CET. All patients were HIV negative female, with age ranging from 50 to 70 years old. Cetuximab (400mg/m2 for week one followed by 250mg/m2 weekly) was used as third line treatment for all the patients; 3 patients had received 5-fluououracil (5FU) + mitomycin and 5 patients 5FU + cisplatin as previous regimens. CET was used concomitant to salvage radiation therapy in one patient, in combination with carboplatin and paclitaxel in 1 patient and combined with irinotecan in 3 patients. Treatment duration time ranged from 45 days to 8 months. Regarding treatment response, 1 patient achieved stable disease, and 4 patients had progression of disease. Mean TTP was 4.2 months (2 to 13 m). One patient out of 5 had KRAS exon 1 mutation (codon 12,GGT⋄GTT). TTP for patient with mutated KRAS was 2 months and for those with wild type ranged from 2 months (3 patients) to 13 months (1 patient).Conclusion: Our data showed that, for heavily treated patients, Cetuximab in third line benefited 1 out of 5 patients (20%), with a long TTP (13 months). No standard second or third line chemotherapy regimens are available for patients with relapsed disease after 5FU, Mitomycin and Cisplatin therapy, and the response rates shown by small trials are disappointing. In accordance with the literature, our study found only 1 mutation in the KRAS gene. In previously treated SCAC, Cetuximab in third line resulted in 20% (1 out 5) disease control in a patient with wild type KRAS. The efficacy of Cetuximab in combination with chemotherapy should be evaluated in future trial and in first and second line of treatment. Background: EGFR protein expression in SCAC is frequent and low rate of KRAS mutation has been described. As a result, Cetuximab would be a putative anti-EGFR agent for treatment of SCAC. No robust data are available about the efficacy of CET for this rare disease. The objective is to evaluate the activity of Cetuximab (CET) for metastatic squamous cell anal carcinoma (SCAC) in third line of treatment and correlate with KRAS mutation status. Methods: We retrospectively analyzed patients treated at our institution with CET. Variables such as age, gender, HIV infection, and treatment combination were evaluated. KRAS status was obtained by DNA pyrosequencing method of exon 1 on the primary tumor sample. We considered time to progression (TTP) as the main end-point for efficacy. Results: We identified 5 patients treated with CET. All patients were HIV negative female, with age ranging from 50 to 70 years old. Cetuximab (400mg/m2 for week one followed by 250mg/m2 weekly) was used as third line treatment for all the patients; 3 patients had received 5-fluououracil (5FU) + mitomycin and 5 patients 5FU + cisplatin as previous regimens. CET was used concomitant to salvage radiation therapy in one patient, in combination with carboplatin and paclitaxel in 1 patient and combined with irinotecan in 3 patients. Treatment duration time ranged from 45 days to 8 months. Regarding treatment response, 1 patient achieved stable disease, and 4 patients had progression of disease. Mean TTP was 4.2 months (2 to 13 m). One patient out of 5 had KRAS exon 1 mutation (codon 12,GGT⋄GTT). TTP for patient with mutated KRAS was 2 months and for those with wild type ranged from 2 months (3 patients) to 13 months (1 patient). Conclusion: Our data showed that, for heavily treated patients, Cetuximab in third line benefited 1 out of 5 patients (20%), with a long TTP (13 months). No standard second or third line chemotherapy regimens are available for patients with relapsed disease after 5FU, Mitomycin and Cisplatin therapy, and the response rates shown by small trials are disappointing. In accordance with the literature, our study found only 1 mutation in the KRAS gene. In previously treated SCAC, Cetuximab in third line resulted in 20% (1 out 5) disease control in a patient with wild type KRAS. The efficacy of Cetuximab in combination with chemotherapy should be evaluated in future trial and in first and second line of treatment.