title: Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope.
abstract: BACKGROUND
  No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in "frail" elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC.
  
  
  METHODS
  Forty elderly patients (aged ≥ 75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.
  
  
  RESULTS
  The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9-8 months) and 14.3 months (95% CI: 10.9-17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%.
  
  
  CONCLUSIONS
  Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data.
  
  
  CONCLUSIONS
  Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could help select an elderly and unfit population that could benefit from anti-epidermal growth factor receptor single agent therapy. In the present study, single-agent off-label panitumumab was effective and well-tolerated as first-line treatment in frail elderly patients deemed unfit for chemotherapy for metastatic RAS and BRAF wild-type colorectal cancer.
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy filippo.pietrantonio@istitutotumori.mi.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cremolini
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Unità Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Medical Oncology Unit, Policlinico Universitario "A. Gemelli," Rome, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Mennitto
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Berenato
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Antoniotti
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Casagrande
authors.affiliation: Unità Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marsico
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marmorino
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
authors.forename: Giovanni Gerardo
authors.initials: GG
authors.lastname: Cardellino
authors.affiliation: Unità Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bergamo
authors.affiliation: Azienda Istituti Ospitalieri di Cremona, Cremona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
authors.affiliation: Unità di Oncologia Medica, Policlinico Universitario Tor Vergata, Roma, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Formica
authors.affiliation: Oncology Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Longarini
authors.affiliation: Struttura Complessa Oncologia Medica I, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giommoni
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Caporale
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004348:Drug Labeling; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology; D005260:Female; D016330:Frail Elderly; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins
keywords: Elderly; Frail; Metastatic colorectal cancer; Panitumumab