F Ciardiello1, N Normanno2, E Martinelli3, T Troiani3, S Pisconti4, C Cardone3, A Nappi3, A R Bordonaro5, M Rachiglio6, M Lambiase6, T P Latiano7, G Modoni4, S Cordio5, F Giuliani8, M Biglietto9, V Montesarchio10, C Barone11, G Tonini12, S Cinieri13, A Febbraro14, D Rizzi15, F De Vita3, M Orditura3, G Colucci8, E Maiello7. 1. Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples fortunato.ciardiello@unina2.it. 2. Cell Biology and Biotherapy Unit, National Cancer Institute 'Fondazione Giovanni Pascale', Naples. 3. Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples. 4. Medical Oncology, Hospital SS. Annunziata, Taranto. 5. Medical Oncology, Hospital Garibaldi, Nesima, Catania. 6. Cell Biology and Biotherapy Unit, National Cancer Institute 'Fondazione Giovanni Pascale', Naples Laboratory of Pharmacogenomics, Centro di Ricerche Oncologiche di Mercogliano (CROM)-National Cancer Institute 'Fondazione Giovanni Pascale', Naples. 7. Medical Oncology, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (Foggia). 8. Medical Oncology, National Cancer Institute Giovanni Paolo II, Bari. 9. Medical Oncology, Hospital 'A. Cardarelli', Naples. 10. Medical Oncology, Hospital Monaldi- Azienda Ospedaliera dei Colli, Naples. 11. Medical Oncology, University Hospital A. Gemelli, Rome. 12. Policlinico Universitario Campus Bio-Medico, Rome. 13. Medical Oncology, Hospital A. Perrino, Brindisi. 14. Medical Oncology, Hospital Sacro Cuore di Gesù, Fatebenefratelli, Benevento. 15. GOIM Trial Office, Bari, Italy.
Abstract
BACKGROUND:Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. PATIENTS AND METHODS: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. RESULTS:Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. CONCLUSIONS: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
RCT Entities:
BACKGROUND:Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. PATIENTS AND METHODS: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRCpatients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. RESULTS: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. CONCLUSIONS: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
Authors: E Martinelli; C Cardone; T Troiani; N Normanno; S Pisconti; V Sforza; A R Bordonaro; A M Rachiglio; M Lambiase; T P Latiano; G Modoni; S Cordio; F Giuliani; M Biglietto; V Montesarchio; C Barone; G Tonini; S Cinieri; A Febbraro; D Rizzi; F De Vita; M Orditura; G Colucci; E Maiello; F Ciardiello Journal: ESMO Open Date: 2017-02-20