Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment of <i>RAS</i> and <i>BRAF</i> Wild-Type Metastatic Colorectal Cancer: The IMPROVE Trial
Abstract
PURPOSE To investigate whether intermittent treatment after an induction phase of first-line schedule of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus panitumumab (PAN) prevents or delays the onset of resistance and improves safety and compliance with treatment in patients with unresectable RAS / BRAF wild-type (wt) metastatic colorectal cancer (mCRC). PATIENTS AND METHODS IMPROVE (ClinicalTrials.gov identifier: NCT04425239 ) was an open-label, multicenter, randomized phase II noncomparative trial. Patients with unresectable RAS / BRAF wt mCRC were randomly assigned (1:1) to receive FOLFIRI plus PAN continuously until progression (arm A) or intermittently, with treatment-free intervals (arm B) until progression on treatment, toxicity, or death. The primary end point was progression-free survival on treatment (PFSot) at 12 months. Assuming a null hypothesis of median PFSot time ≤7 months and target PFSot ≥10 months, 65 patients per arm were needed to achieve 80% power and 10% type I error, according to the binomial test. RESULTS Between May 2018 and June 2021, 69 patients were randomly assigned to arm A and 68 to arm B. The median number of treatment cycles was 13 in arm A and 16 in arm B. At a median follow-up of 43.2 months (IQR, 35.0-50.5), median PFSot was 11.2 and 17.5 months with 12-month PFSot rates of 45.7% and 58.5%, for arms A and B, respectively. The overall response rates were 68.1% and 61.2%, and median overall survival rates were 36.3 and 35.1 months in arms A and B, respectively. The overall rate of grade >2 skin PAN-related adverse events was 30.3% in arm A and 17.9% in arm B. CONCLUSION Intermittent FOLFIRI plus PAN after the induction phase was feasible, and the primary end point was met with reduced toxicity while allowing patients more time off treatment.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (26)
Antonio Avallone
Antonio Avallone, MD, and Alfonso De Stefano, MD, PhD, Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Napoli, Italy; and Davide Ciardiello, MD, PhD, Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
Francesco Giuliani
Medical Oncology Irccs Giovanni Paolo II Bari and Medical Oncology San Paolo Hospital ASL, Bari, Italy
Alfonso De Stefano
Antonio Avallone, MD, and Alfonso De Stefano, MD, PhD, Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Napoli, Italy; and Davide Ciardiello, MD, PhD, Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
Giuseppe Santabarbara
Oncology Unit, San Giuseppe Moscati Hospital, Avellino, Italy
Guglielmo Nasti
Vincenzo Montesarchio
UOC Oncologia Medica, AORN dei colli-Monaldi, Napoli, Italy
Gerardo Rosati
Antonino Cassata
Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Napoli, Italia
Silvana Leo
Medical Oncology Unit, Ospedale Vito Fazzi, Lecce, Italy
Carmela Romano
Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Napoli, Italia
Emiliano Tamburini
Oncology Department and Palliative Care, Cardinale Panico Tricase City Hospital, Tricase, Italy
Lucrezia Silvestro
Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Napoli, Italia
Claudio Lotesoriere
Medical Oncology Unit, IRCCS Saverio de Bellis Hospital, Castellana Grotte, Italy
Anna Nappi
Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Napoli, Italia
Daniele Santini
Antonella Petrillo
Radiology Unit, Istituto Nazionale Tumori-IRCCS—Fondazione G. Pascale, Napoli, Italia
Alfredo Colombo
Medical Oncology, Casa di Cura Macchiarella, Palermo, Italy
Antonio Febbraro
Medical Oncology Unit, Ospedale Sacro Cuore di Gesù-Fatebenefratelli, Benevento, Italy
Alessandra Leone
Experimental Pharmacology Unit, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Napoli, Italia
Francesco Mannavola
5Medical Oncology Unit, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
maria Maddalena Laterza
Oncology Complex Unit, Santa Maria delle Grazie Hospital, Pozzuoli, naples, Italy
Francesco Izzo
Alberto Sobrero
8Medical Oncology Unit, IRCCS San Martino General Hospital, Genoa, Italy
Paolo Delrio
Diana Giannarelli
Alfredo Budillon