PMID- 34416469 OWN - NLM STAT- MEDLINE DCOM- 20211029 LR - 20240403 IS - 2059-7029 (Electronic) IS - 2059-7029 (Linking) VI - 6 IP - 5 DP - 2021 Oct TI - Impact of age and gender on the efficacy and safety of upfront therapy with panitumumab plus FOLFOX followed by panitumumab-based maintenance: a pre-specified subgroup analysis of the Valentino study. PG - 100246 LID - S2059-7029(21)00207-6 [pii] LID - 10.1016/j.esmoop.2021.100246 [doi] LID - 100246 AB - BACKGROUND: The safety and efficacy outcome of elderly metastatic colorectal cancer (mCRC) patients fit enough to receive combination chemotherapy plus biological agents is an issue of growing interest. Also, gender-specific differential toxicity and efficacy of anti-epidermal growth factor receptor (EGFR)-based upfront treatments need to be explored. PATIENTS AND METHODS: Valentino was a multicenter, randomized, phase II trial, investigating two panitumumab-based maintenance strategies following first-line panitumumab plus FOLFOX in RAS wild-type mCRC patients. We carried out a subgroup analysis, aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus >/=70 years) and gender (male versus female). Efficacy endpoints were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR); safety endpoints were rates of any grade and grade 3/4 adverse events (AEs). RESULTS: No significant differences in terms of PFS, OS and ORR were observed between patients aged <70 or >/=70 years and the effect of the maintenance treatment arm on survival outcomes was similar in the two subgroups. The safety profile of both induction and maintenance treatment and the impact on QoL were similar in elderly and younger patients. No significant differences in PFS, OS, ORR or clinical benefit rate were observed according to gender. A significantly higher rate of overall grade 3/4 AEs (P = 0.008) and of grade 3/4 thrombocytopenia (P = 0.017), any grade and grade 3/4 neutropenia (P < 0.0001) and any grade conjunctivitis (P = 0.033) was reported in female as compared to male patients. Conversely, we reported a significantly higher incidence of any grade skin rash (P = 0.0007) and hypomagnesemia (P = 0.029) in male patients. CONCLUSIONS: The upfront choice of an anti-EGFR-based doublet chemotherapy followed by a maintenance strategy represents a valuable option in RAS wild-type mCRC irrespective of gender and age, though a careful evaluation of patients to maximize the risk/benefit ratio is warranted. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Raimondi, A AU - Raimondi A AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Fuca, G AU - Fuca G AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Leone, A G AU - Leone AG AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Lonardi, S AU - Lonardi S AD - Medical Oncology Unit 3, Department of Oncology, Istituto Oncologico Veneto-IRCCS, Padua, Italy. FAU - Antoniotti, C AU - Antoniotti C AD - Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Smiroldo, V AU - Smiroldo V AD - Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Amatu, A AU - Amatu A AD - Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Tampellini, M AU - Tampellini M AD - Department of Oncology, AOU San Luigi di Orbassano, University of Torino, Orbassano, Italy. FAU - Ritorto, G AU - Ritorto G AD - SSD ColoRectal Cancer Unit, Oncology Department, Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza, Torino, Italy. FAU - Murialdo, R AU - Murialdo R AD - Department of Internal Medicine, University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy. FAU - Clavarezza, M AU - Clavarezza M AD - Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy. FAU - Zaniboni, A AU - Zaniboni A AD - Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy. FAU - Berenato, R AU - Berenato R AD - Medical Oncology Unit, A.O. Papardo, Messina, Italy. FAU - Ratti, M AU - Ratti M AD - Medical Oncology Unit, ASST Ospedale di Cremona, Cremona, Italy. FAU - Corallo, S AU - Corallo S AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Morano, F AU - Morano F AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Di Bartolomeo, M AU - Di Bartolomeo M AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Di Maio, M AU - Di Maio M AD - Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Torino, Italy. FAU - Pietrantonio, F AU - Pietrantonio F AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: filippo.pietrantonio@istitutotumori.mi.it. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210817 PL - England TA - ESMO Open JT - ESMO open JID - 101690685 RN - 6A901E312A (Panitumumab) RN - U3P01618RT (Fluorouracil) SB - IM MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - *Colorectal Neoplasms/drug therapy MH - Female MH - Fluorouracil/adverse effects MH - Humans MH - Male MH - Panitumumab/therapeutic use MH - *Quality of Life PMC - PMC8379288 OTO - NOTNLM OT - age OT - anti-EGFR OT - colorectal cancer OT - gender OT - metastasis COIS- Disclosure FP has received honoraria for speaker activities and participation in advisory boards from Sanofi, Amgen, Bayer, Merck-Serono, Lilly, Roche and Servier and research grants from BMS. SL has received honoraria for speaker activities and participation in advisory boards from Amgen, Bayer, Merck-Serono, Roche, Servier and Bristol-Myers Squibb. AZ has received honoraria for speaker bureau from Amgen, Merck, Servier and Bayer. SC has received honoraria for participation in advisory boards from Merck. MDB has received honoraria for speaker activities and participation in advisory boards from Amgen, Roche, Lilly, Servier, Incyte and Celgene. FM has received honoraria for speaker activities from Servier. The remaining authors have declared no conflicts of interest. EDAT- 2021/08/21 06:00 MHDA- 2021/10/30 06:00 PMCR- 2021/08/17 CRDT- 2021/08/20 20:18 PHST- 2021/06/23 00:00 [received] PHST- 2021/07/23 00:00 [revised] PHST- 2021/07/28 00:00 [accepted] PHST- 2021/08/21 06:00 [pubmed] PHST- 2021/10/30 06:00 [medline] PHST- 2021/08/20 20:18 [entrez] PHST- 2021/08/17 00:00 [pmc-release] AID - S2059-7029(21)00207-6 [pii] AID - 100246 [pii] AID - 10.1016/j.esmoop.2021.100246 [doi] PST - ppublish SO - ESMO Open. 2021 Oct;6(5):100246. doi: 10.1016/j.esmoop.2021.100246. Epub 2021 Aug 17.