PMID- 31268481
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220422
IS  - 2374-2445 (Electronic)
IS  - 2374-2437 (Print)
IS  - 2374-2437 (Linking)
VI  - 5
IP  - 9
DP  - 2019 Sep 1
TI  - Maintenance Therapy With Panitumumab Alone vs Panitumumab Plus 
      Fluorouracil-Leucovorin in Patients With RAS Wild-Type Metastatic Colorectal 
      Cancer: A Phase 2 Randomized Clinical Trial.
PG  - 1268-1275
LID - 10.1001/jamaoncol.2019.1467 [doi]
AB  - IMPORTANCE: Few studies are available on the role of maintenance strategies after 
      induction treatment regimens based on anti-epidermal growth factor receptors, and 
      the optimal regimen for an anti-epidermal growth factor receptors-based 
      maintenance treatment in patients with RAS wild-type metastatic colorectal cancer 
      is still to be defined. OBJECTIVE: To determine whether maintenance therapy with 
      single-agent panitumumab was noninferior to panitumumab plus fluorouracil and 
      leucovorin after a 4-month induction treatment regimen. DESIGN, SETTING, AND 
      PARTICIPANTS: This open-label, randomized phase 2 noninferiority trial was 
      conducted from July 7, 2015, through October 27, 2017, at multiple Italian 
      centers. Patients with RAS wild-type, unresectable metastatic colorectal 
      adenocarcinoma who had not received previous treatment for metastatic disease 
      were eligible. Induction therapy consisted of panitumumab plus FOLFOX-4 
      (panitumumab, 6 mg/kg, oxaliplatin, 85 mg/m2 at day 1, leucovorin calcium, 200 
      mg/m2, and fluorouracil, 400-mg/m2 bolus, followed by 600-mg/m2 continuous 
      24-hour infusion at days 1 and 2, every 2 weeks). Cutoff date for analyses was 
      July 30, 2018. INTERVENTIONS: Patients were randomized (1:1) to first-line 
      panitumumab plus FOLFOX-4 for 8 cycles followed by maintenance therapy with 
      panitumumab plus fluorouracil-leucovorin (arm A) or panitumumab (arm B) until 
      progressive disease, unacceptable toxic effects, or consent withdrawal. The 
      minimization method was used to stratify randomization by previous adjuvant 
      treatment and number of metastatic sites. MAIN OUTCOMES AND MEASURES: The 
      prespecified primary end point was 10-month progression-free survival (PFS) 
      analyzed on an intention-to-treat basis with a noninferiority margin of 1.515 for 
      the upper limit of the 1-sided 90% CI of the hazard ratio (HR) of arm B vs A. 
      RESULTS: Overall, 229 patients (153 male [66.8%]; median age, 64 years 
      [interquartile range (IQR), 56-70 years]) were randomly assigned to arm A 
      (n = 117) or arm B (n = 112). At a median follow-up of 18.0 months (IQR, 
      13.1-23.3 months]), a total of 169 disease progression or death events occurred. 
      Arm B was inferior (upper limit of 1-sided 90% CI of the HR, 1.857). Ten-month 
      PFS was 59.9% (95% CI, 51.5%-69.8%) in arm A vs 49.0% (95% CI, 40.5%-59.4%) in 
      arm B (HR, 1.51; 95% CI, 1.11-2.07; P = .01). During maintenance, arm A had a 
      higher incidence of grade 3 or greater treatment-related adverse events (36 
      [42.4%] vs 16 [20.3%]) and panitumumab-related adverse events (27 [31.8%] vs 13 
      [16.4%]), compared with arm B. CONCLUSIONS AND RELEVANCE: In patients with RAS 
      wild-type metastatic colorectal cancer, maintenance therapy with single-agent 
      panitumumab was inferior in terms of PFS compared with panitumumab plus 
      fluorouracil-leucovorin, which slightly increased the treatment toxic effects. 
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02476045.
FAU - Pietrantonio, Filippo
AU  - Pietrantonio F
AD  - Oncology and Hemato-oncology Department, University of Milan, Milan, Italy.
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - Morano, Federica
AU  - Morano F
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - Corallo, Salvatore
AU  - Corallo S
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - Miceli, Rosalba
AU  - Miceli R
AD  - Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale 
      dei Tumori, Milan, Italy.
FAU - Lonardi, Sara
AU  - Lonardi S
AD  - Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, 
      Istituto Oncologico Veneto, IRCCS, Padua, Italy.
FAU - Raimondi, Alessandra
AU  - Raimondi A
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - Cremolini, Chiara
AU  - Cremolini C
AD  - Unit of Medical Oncology, Azienda Ospedaliero-Universitaria (AOU) Pisana, 
      Department of Translational Research and New Technologies in Medicine, University 
      of Pisa, Pisa, Italy.
FAU - Rimassa, Lorenza
AU  - Rimassa L
AD  - Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical 
      and Research Center, Rozzano, Italy.
FAU - Bergamo, Francesca
AU  - Bergamo F
AD  - Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, 
      Istituto Oncologico Veneto, IRCCS, Padua, Italy.
FAU - Sartore-Bianchi, Andrea
AU  - Sartore-Bianchi A
AD  - Oncology and Hemato-oncology Department, University of Milan, Milan, Italy.
AD  - Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
FAU - Tampellini, Marco
AU  - Tampellini M
AD  - Department of Oncology, AOU San Luigi di Orbassano, University of Torino, 
      Orbassano, Italy.
FAU - Racca, Patrizia
AU  - Racca P
AD  - Colorectal Cancer Unit, Medical Oncology Division 1, AOU Citta della Salute e 
      della Scienza, Torino, Italy.
FAU - Clavarezza, Matteo
AU  - Clavarezza M
AD  - Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy.
FAU - Berenato, Rosa
AU  - Berenato R
AD  - Medical Oncology Unit A.O. Papardo and Department of Human Pathology, University 
      of Messina, Messina, Italy.
FAU - Caporale, Marta
AU  - Caporale M
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - Antista, Maria
AU  - Antista M
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - Niger, Monica
AU  - Niger M
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - Smiroldo, Valeria
AU  - Smiroldo V
AD  - Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical 
      and Research Center, Rozzano, Italy.
FAU - Murialdo, Roberto
AU  - Murialdo R
AD  - Department of Internal Medicine, University of Genoa and IRCCS AOU San 
      Martino-IST, Genoa, Italy.
FAU - Zaniboni, Alberto
AU  - Zaniboni A
AD  - Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy.
FAU - Adamo, Vincenzo
AU  - Adamo V
AD  - Medical Oncology Unit A.O. Papardo and Department of Human Pathology, University 
      of Messina, Messina, Italy.
FAU - Tomasello, Gianluca
AU  - Tomasello G
AD  - Medical Oncology Unit, Azienda Socio-Sanitaria Territoriale (ASST) Ospedale di 
      Cremona, Cremona, Italy.
FAU - Giordano, Monica
AU  - Giordano M
AD  - Medical Oncology Unit, Azienda Socio Sanitaria Territoriale Lariana, Como, Italy.
FAU - Petrelli, Fausto
AU  - Petrelli F
AD  - Medical Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio, Italy.
FAU - Longarini, Raffaella
AU  - Longarini R
AD  - Medical Oncology Unit, Azienda Ospedaliera San Gerardo, Monza, Italy.
FAU - Cinieri, Saverio
AU  - Cinieri S
AD  - Medical Oncology Unit, Ospedale Antonio Perrino, Brindisi, Italy.
FAU - Falcone, Alfredo
AU  - Falcone A
AD  - Unit of Medical Oncology, Azienda Ospedaliero-Universitaria (AOU) Pisana, 
      Department of Translational Research and New Technologies in Medicine, University 
      of Pisa, Pisa, Italy.
FAU - Zagonel, Vittorina
AU  - Zagonel V
AD  - Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, 
      Istituto Oncologico Veneto, IRCCS, Padua, Italy.
FAU - Di Bartolomeo, Maria
AU  - Di Bartolomeo M
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
FAU - de Braud, Filippo
AU  - de Braud F
AD  - Oncology and Hemato-oncology Department, University of Milan, Milan, Italy.
AD  - Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT02476045
PT  - Journal Article
PL  - United States
TA  - JAMA Oncol
JT  - JAMA oncology
JID - 101652861
SB  - IM
CIN - doi: 10.1001/jamaoncol.2019.1447
PMC - PMC6613306
COIS- Conflict of Interest Disclosures: Dr Peitrantonio reported receiving honoraria 
      for speaker activities and participation in advisory boards from Sanofi SA, 
      Amgen, Inc, Bayer AG, Merck-Serono, Roche, and Servier Laboratories. Dr Lombardi 
      reported receiving honoraria for speaker activities and participation in advisory 
      boards from Amgen, Inc, Bayer AG, Merck-Serono, Roche, Servier Laboratories, and 
      Bristol-Myers Squibb. Dr Cremolini reported receiving honoraria for speaker 
      activities and participation in advisory boards from Roche, Amgen, Inc, Bayer AG, 
      and Servier Laboratories and research grants from Merck-Serono. Dr Rimassa 
      reported receiving honoraria for speaker activities and participation in advisory 
      boards from AstraZeneca, AbbVie, Eli Lilly and Company, Bayer AG, Sirtex Medical 
      Limited, Italfarmaco SpA, Sanofi SA, ArQule, Inc, Baxter International, Inc, 
      Ipsen, Exelixis, Inc, Amgen, Inc, Incyte Corp, and Celgene Corporation. Dr 
      Sartore-Bianchi reported receiving honoraria for speaker activities and 
      participation in advisory boards from Sanofi SA, Amgen, Inc, Bayer AG, 
      Merck-Serono, and Roche. Dr Zaniboni reported receiving honoraria for speaker 
      activities and participation in advisory boards from Sanofi SA, Amgen, Inc, Bayer 
      AG, Merck-Serono, and Roche. Dr Di Bartolomeo reported receiving honoraria for 
      speaker activities and participation in advisory boards from Amgen, Inc, Roche, 
      Eli Lilly and Company, Servier Laboratories. Incyte Corp, and Celgene 
      Corporation. Dr de Braud reported receiving honoraria for speaker activities and 
      participation in advisory boards from Amgen, Inc, Roche, and Novartis 
      International AG. No other disclosures were reported.
EDAT- 2019/07/04 06:00
MHDA- 2019/07/04 06:01
PMCR- 2019/07/03
CRDT- 2019/07/04 06:00
PHST- 2019/07/04 06:00 [pubmed]
PHST- 2019/07/04 06:01 [medline]
PHST- 2019/07/04 06:00 [entrez]
PHST- 2019/07/03 00:00 [pmc-release]
AID - 2737075 [pii]
AID - coi190038 [pii]
AID - 10.1001/jamaoncol.2019.1467 [doi]
PST - ppublish
SO  - JAMA Oncol. 2019 Sep 1;5(9):1268-1275. doi: 10.1001/jamaoncol.2019.1467.