PMID- 26446234 OWN - NLM STAT- MEDLINE DCOM- 20160822 LR - 20220408 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 20 IP - 11 DP - 2015 Nov TI - Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope. PG - 1261-5 LID - 10.1634/theoncologist.2015-0171 [doi] AB - 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. MATERIALS AND 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%. CONCLUSION: 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. IMPLICATIONS FOR PRACTICE: 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. CI - (c)AlphaMed Press. FAU - Pietrantonio, Filippo AU - Pietrantonio F AD - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy filippo.pietrantonio@istitutotumori.mi.it. FAU - Cremolini, Chiara AU - Cremolini C AD - Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Aprile, Giuseppe AU - Aprile G AD - Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy. FAU - Lonardi, Sara AU - Lonardi S AD - Unita Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy. FAU - Orlandi, Armando AU - Orlandi A AD - Medical Oncology Unit, Policlinico Universitario "A. Gemelli," Rome, Italy. FAU - Mennitto, Alessia AU - Mennitto A AD - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Berenato, Rosa AU - Berenato R AD - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Antoniotti, Carlotta AU - Antoniotti C AD - Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Casagrande, Mariaelena AU - Casagrande M AD - Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy. FAU - Marsico, Valentina AU - Marsico V AD - Unita Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy. FAU - Marmorino, Federica AU - Marmorino F AD - Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Cardellino, Giovanni Gerardo AU - Cardellino GG AD - Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy. FAU - Bergamo, Francesca AU - Bergamo F AD - Unita Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy. FAU - Tomasello, Gianluca AU - Tomasello G AD - Azienda Istituti Ospitalieri di Cremona, Cremona, Italy. FAU - Formica, Vincenzo AU - Formica V AD - Unita di Oncologia Medica, Policlinico Universitario Tor Vergata, Roma, Italy. FAU - Longarini, Raffaella AU - Longarini R AD - Oncology Unit, San Gerardo Hospital, Monza, Italy. FAU - Giommoni, Elisa AU - Giommoni E AD - Struttura Complessa Oncologia Medica I, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy. FAU - Caporale, Marta AU - Caporale M AD - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Di Bartolomeo, Maria AU - Di Bartolomeo M AD - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Loupakis, Fotios AU - Loupakis F AD - Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - de Braud, Filippo AU - de Braud F AD - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. LA - eng PT - Journal Article DEP - 20151007 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antibodies, Monoclonal) RN - 6A901E312A (Panitumumab) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (BRAF protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) RN - EC 3.6.5.2 (ras Proteins) SB - IM MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Colorectal Neoplasms/*drug therapy/genetics/pathology MH - Disease-Free Survival MH - Drug Labeling MH - ErbB Receptors/antagonists & inhibitors/immunology MH - Female MH - Frail Elderly MH - Humans MH - Kaplan-Meier Estimate MH - Male MH - Neoplasm Metastasis MH - Panitumumab MH - Proto-Oncogene Proteins B-raf/*genetics MH - ras Proteins/*genetics PMC - PMC4718427 OTO - NOTNLM OT - Elderly OT - Frail OT - Metastatic colorectal cancer OT - Panitumumab COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2015/10/09 06:00 MHDA- 2016/08/23 06:00 PMCR- 2016/11/01 CRDT- 2015/10/09 06:00 PHST- 2015/03/26 00:00 [received] PHST- 2015/08/21 00:00 [accepted] PHST- 2015/10/09 06:00 [entrez] PHST- 2015/10/09 06:00 [pubmed] PHST- 2016/08/23 06:00 [medline] PHST- 2016/11/01 00:00 [pmc-release] AID - theoncologist.2015-0171 [pii] AID - T15171 [pii] AID - 10.1634/theoncologist.2015-0171 [doi] PST - ppublish SO - Oncologist. 2015 Nov;20(11):1261-5. doi: 10.1634/theoncologist.2015-0171. Epub 2015 Oct 7.