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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3035 - Intermittent or continuous Panitumumab (PAN) plus FOLFIRI for first-line treatment of patients (pts) with RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC): a randomized phase 2 trial (IMPROVE)


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Clinical Research;  Targeted Therapy

Tumour Site

Colon and Rectal Cancer


Alfonso De Stefano


Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281


A. De Stefano1, G. Nasti2, A. Febbraro3, G. Rosati4, F. Giuliani5, D. Santini6, G. Aprile7, M. Scartozzi8, F. Silvestris9, G. Luppi10, I. Lolli11, C. Mastroianni12, S. Leo13, V. Montesarchio14, C. Gridelli15, C. Pozzo16, E. Sperti17, D. Giannarelli18, A. Budillon19, A. Avallone1

Author affiliations

  • 1 Clinical Experimental Abdominal Oncology Unit, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
  • 2 Ssd Innovative Therapies For Abdominal Metastases - Abdominal Oncology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
  • 3 Medical Oncology, Ospedale "Sacro Cuore di Gesù" Fatebenefratelli, 82100 - Benevento/IT
  • 4 Oncology, ospedale San Carlo, Potenza/IT
  • 6 Oncology, Campus Bio-Medico di Roma, 128 - Rome/IT
  • 7 Medical Oncology, ULSS 8 Berica - Vicenza, 36100 - Vicenza/IT
  • 8 Oncology, University Hospital and University of Cagliari, cagliari/IT
  • 9 Department Of Biomedical Sciences And Human Oncology – University Of Bari, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, 70124 - Bari/IT
  • 10 Medical Oncology, Azienda Ospedaliero Universitaria di Modena, Modena/IT
  • 11 Medical Oncology Unit, IRCCS Saverio de Bellis, Castellana Grotte/IT
  • 12 Medical Oncology, Azienda Ospedaliera di Cosenza, Cosenza/IT
  • 13 Medical Oncology, Ospedale Vito Fazzi, Lecce/IT
  • 14 Medical Oncology, Azienda Ospedaliera Dei Colli-Monaldi, 80131 - Napoli/IT
  • 15 Medical Oncology, Azienda Ospedaliera S. Giuseppe Moscati, 83100 - Avellino/IT
  • 16 Oncologia Medica - Fondazione Policlinico Gemelli - Irccs, Università Cattolica del Sacro Cuore, 00168 - Rome/IT
  • 17 Medical Oncology, Ordine Mauriziano Hospital, Turin/IT
  • 18 Statistica, IFO Regina Elena Roma, Roma/IT
  • 19 Clinical Pharmacology Experimental, Istituto Nazionale Tumori, IRCCS, Fondazione "G. Pascale", 80131 - Naples/IT


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Abstract 3035


Anti-EGFR treatment demonstrated a clinical benefit limited to RAS-wt mCRC pts. In the FIRE-3 trial the depth of response was significantly associated with survival and the median time to tumor nadir was of 3.6months in the FOLFIRI plus anti-EGFR arm. These data suggest that further exposure to combined treatment may not result in an outcome improvement, but only in an increase of side effects. Therefore, a drug holiday strategy could increase adherence to therapy and quality of life. The feasibility of intermittent use of FOLFIRI in first line was showed by the GISCAD study, but no data are available on the optimal duration of anti-EGFR monoclonal antibodies (moAbs). This issue is of particular interest given the dermatologic toxicities of anti-EGFR moAbs and the emergence of drug resistant clones. In mCRC pts recent data suggest a molecular adaptation of tumor to an intermittent drug schedule with anti-EGFR moAbs. On this basis, we designed a multicenter phase II randomized two arms study with intermittent PAN plus FOLFIRI compared to the same regimen given continuously until disease progression (PD) in the first line treatment of pts with WT RAS and BRAF unresectable mCRC, with a prospective genetic analysis of both tumor tissue and cfDNA.

Trial design

PFS on treatment (PFSOT) at 12months is the primary endpoint. Assuming a p0=30% (corresponding to a median PFS of 7months), and a p1=43% (corresponding to a median PFS of 10months), setting the significance level at 10% with a power of 80% a total of 68 pts will be enrolled in each arm. At the time of enrollment, pts will be immediately randomized to one of the two arms: standard continuous or exploratory intermittent treatment. All pts will receive an induction treatment with 8 cycles of PAN plus FOLFIRI, given every two weeks, at the standard dosage. After the induction treatment, non-progressing pts will receive continuous PAN plus FOLFIRI until PD, unacceptable toxicity or informed consent withdrawal (Standard ARM) or observe a treatment free interval until PD followed by up to 8 cycles of PAN plus FOLFIRI (Experimental ARM). Treatment cycling will continue till any PD on treatment.

Clinical trial identification

EudraCT: 2017-003628-65.

Legal entity responsible for the study

Istituto Nazionale Tumori Fondazione G. Pascale - Naples, Italy.


Amgen; Istituto Nazionale Tumori Fondazione G. Pascale - Naples, Italy

Editorial Acknowledgement



A. De Stefano: Advisory boards: Amgen, Roche. G. Rosati: Advisory role: Amgen, Roche, Bayer, Merck Serono. A. Avallone: Advisory role: Roche, Amgen, Celgene, Sanofi; Research funding: Bayer. All other authors have declared no conflicts of interest.

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