+1 Recommend
0 collections
      • Record: found
      • Abstract: not found
      • Article: not found

      Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan : A Phase 2 Single-Arm Clinical Trial

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Based on a small retrospective study, rechallenge with cetuximab-based therapy for patients with KRAS wild-type metastatic colorectal cancer (mCRC) who were previously treated with the same anti-epidermal growth factor receptor-based regimen might be efficacious. Recent data suggest the role of liquid biopsy as a tool to track molecular events in circulating tumor DNA (ctDNA).

          Related collections

          Most cited references14

          • Record: found
          • Abstract: found
          • Article: not found

          Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial.

          In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT.
            • Record: found
            • Abstract: found
            • Article: not found

            EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer.

            To determine whether adding cetuximab to irinotecan prolongs survival in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine and oxaliplatin. This multicenter, open-label, phase III study randomly assigned 1,298 patients with epidermal growth factor receptor-expressing mCRC who had experienced first-line fluoropyrimidine and oxaliplatin treatment failure to cetuximab (400 mg/m(2) day 1 followed by 250 mg/m(2) weekly) plus irinotecan (350 mg/m(2) every 3 weeks) or irinotecan alone. Primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR), and quality of life (QOL). Median OS was comparable between treatments: 10.7 months (95% CI, 9.6 to 11.3) with cetuximab/irinotecan and 10.0 months (95% CI, 9.1 to 11.3) with irinotecan alone (hazard ratio [HR], 0.975; 95% CI, 0.854 to 1.114; P = .71). This lack of difference may have been due to post-trial therapy: 46.9% of patients assigned to irinotecan eventually received cetuximab (87.2% of those who did, received it with irinotecan). Cetuximab added to irinotecan significantly improved PFS (median, 4.0 v 2.6 months; HR, 0.692; 95% CI, 0.617 to 0.776; P
              • Record: found
              • Abstract: found
              • Article: found

              Tumour heterogeneity and the evolution of polyclonal drug resistance

              Cancer drug resistance is a major problem, with the majority of patients with metastatic disease ultimately developing multidrug resistance and succumbing to their disease. Our understanding of molecular events underpinning treatment failure has been enhanced by new genomic technologies and pre-clinical studies. Intratumour genetic heterogeneity (ITH) is a prominent contributor to therapeutic failure, and it is becoming increasingly apparent that individual tumours may achieve resistance via multiple routes simultaneously - termed polyclonal resistance. Efforts to target single resistance mechanisms to overcome therapeutic failure may therefore yield only limited success. Clinical studies with sequential analysis of tumour material are needed to enhance our understanding of inter-clonal functional relationships and tumour evolution during therapy, and to improve drug development strategies in cancer medicine.

                Author and article information

                JAMA Oncology
                JAMA Oncol
                American Medical Association (AMA)
                November 21 2018
                [1 ]Unit of Medical Oncology 2, Department of Translational Research and New Technologies in Medicine and Surgery, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
                [2 ]Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy
                [3 ]Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology Istituto Oncologico Veneto–Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy
                [4 ]Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [5 ]Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, Pisa, Italy
                [6 ]Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [7 ]Department of Oncology, University and General Hospital, Udine, Italy
                [8 ]Department of Oncology, General Hospital San Bortolo, Unità Locale Socio-Sanitaria 8 Berica, Vicenza, Italy
                [9 ]Department of Medical Oncology, Infermi Hospital, Rimini, Italy
                [10 ]Medical Oncology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
                [11 ]Medical Oncology Unit, University Hospital, Parma, Italy
                [12 ]Medical Oncology Unit, Fatebenefratelli–Isola Tiberina Hospital, Rome, Italy
                [13 ]Medical Oncology Unit, Presidio Ospedaliero Felice Lotti, Pontedera, Italy
                © 2018


                Comment on this article