Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment of RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The IMPROVE Trial
Year: 2024
Type: article
Study designs: Randomized Controlled Trial, Clinical 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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco.24.00979
Authors: Antonio Avallone, Francesco Giuliani, Alfonso De Stefano, Giuseppe Santabarbara, Guglielmo Nasti, Vincenzo Montesarchio, Gerardo Rosati, Antonino Cassata, Silvana Leo, Carmela Romano, Emiliano Tamburini, Lucrezia Silvestro, Claudio Lotesoriere, Anna Nappi, Daniele Santini, Antonella Petrillo, Alfredo Colombo, Antonio Febbraro, Alessandra Leone, Francesco Mannavola, Maria Maddalena Laterza, Francesco Izzo, Alberto Sobrero, Paolo Delrio, Diana Giannarelli, Alfredo Budillon
Institutions: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Istituto Tumori Bari, Azienda Ospedaliera S.Giuseppe Moscati, Ospedale San Carlo, Ospedale Vito Fazzi, Pia Fondazione di Culto e Religione Azienda Ospedaliera "Card. G. Panico", Gastroenterology Hospital "Saverio de Bellis", Policlinico Umberto I, Sapienza University of Rome, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, Ospedale Policlinico San Martino, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Amgen
OpenAlex ID: W4404625501