title: First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: A phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours.
abstract: BACKGROUND
  Frail elderly patients with metastatic colorectal cancer (mCRC) are not candidates for chemotherapy. Monotherapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies may be an option for these patients with few systemic toxic effects.
  
  
  METHODS
  Single-arm, multicentre, phase II trial including patients ⩾ 70y ears with wild-type (WT) KRAS (exon 2) mCRC, Eastern Cooperative Oncology Group (ECOG) status ⩽ 3, KPC (Köhne Prognostic Classification)--defined intermediate or high risk status, frailty and/or ineligibility for chemotherapy. Patients received panitumumab until progression or unacceptable toxicity. The primary end-point was progression free survival (PFS) rate at 6 months.
  
  
  RESULTS
  The study included 33 patients (intention-to-treat (ITT) population). Median age: 81 years; sex: 66.7% male; high-risk KPC status: 45.4%. Median treatment duration was 14 weeks and 6-month PFS rate was 36.4% (95% confidence interval (CI): 20.0-52.8). The objective response rate: 9.1% (95% CI: 0-18.9) (all partial responses), and there were 18 stable diseases (54.5%). Median PFS was 4.3 months (95% CI: 2.8-6.4) and median overall survival (OS) was 7.1 months (95% CI: 5.0-12.3). There were no deaths or grade 4-5 adverse events (AEs) related to panitumumab and the most common grade 3-related AE was rash acneiform (15.2%). A significant association between clinical response and RAS status was observed (P=0.037). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS, N = 15), 6-month PFS rate was 53.3% (95% CI: 30.1-75.2) and median PFS and OS were 7.9 and 12.3 months, respectively.
  
  
  CONCLUSIONS
  Single-agent panitumumab is active and well tolerated and may be a therapeutic option for high-risk frail elderly patients with WT RAS tumours considered not candidates for chemotherapy (clinicaltrials.gov identifier NCT01126112).
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, c/Martín Lagos s/n, 28040 Madrid, Spain. Electronic address: jsastre.hcsc@salud.madrid.org.
authors.forename: J
authors.initials: J
authors.lastname: Sastre
authors.affiliation: Medical Oncology Service, Hospital General Universitario de Alicante, Pintor Baeza, 12, 03010 Alicante, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Massuti
authors.affiliation: Oncology Service, Hospital Reina Sofía, University of Córdoba, Maimonides Institute of Biomedical Research (IMIBIC), Avda. Menéndez Pidal, s/n, 14004 Córdoba, Spain; Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, C/ Sinesio Delgado, 4, 28029 Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Pulido
authors.affiliation: Medical Oncology Service, Hospital Ramón y Cajal, Ctra. de Colmenar Viejo, km. 9100, 28034 Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Guillén-Ponce
authors.affiliation: Medical Oncology Service, Hospital Regional Universitario, Avenida Carlos Haya, s/n, 29010 Málaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Benavides
authors.affiliation: Catalan Institute of Oncology Badalona, Hospital Universitario Germans Trias i Pujol, Crta. Can Ruti-Camí Escoles, s/n, 08916 Badalona, Barcelona, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Manzano
authors.affiliation: Medical Oncology Service, Hospital Universitario A Coruña - Hospital Teresa Herrera, As Xubias, s/n, 15006 A Coruña, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Reboredo
authors.affiliation: Medical Oncology Service, Hospital Marqués de Valdecilla, Avenida Valdecilla, s/n, 39008 Santander, Cantabria, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Medical Oncology Service, Hospital 12 de Octubre, Madrid, Avda de Córdoba, s/n, 28041 Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Grávalos
authors.affiliation: Medical Oncology Service, Hospital General Universitario, Av. de les Tres Creus, 2, 46014 Valencia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Safont
authors.affiliation: Catalan Institute of Oncology ĹHospitalet, Hospital Durán i Reynals, Avinguda Granvia de l'Hospitalet, 199-203, 08908 l'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martínez Villacampa
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, c/Martín Lagos s/n, 28040 Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Llovet
authors.affiliation: Medical Oncology Service, Corporació Sanitària Parc Taulí, Parc Taulí 1, 08208 Sabadell, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Dotor
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, c/Martín Lagos s/n, 28040 Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Díaz-Rubio
authors.affiliation: Oncology Service, Hospital Reina Sofía, University of Córdoba, Maimonides Institute of Biomedical Research (IMIBIC), Avda. Menéndez Pidal, s/n, 14004 Córdoba, Spain; Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, C/ Sinesio Delgado, 4, 28029 Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Aranda
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013030:Spain; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Colorectal cancer; Elderly patients; First-line; Frailty; Monotherapy; Panitumumab