{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:30:05Z","timestamp":1787725805227,"version":"build-2784847793"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20\u201325% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9\/19 papillary, 5\/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7\u201311.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.<\/jats:p>","DOI":"10.3390\/ijms24021096","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T02:20:30Z","timestamp":1672971630000},"page":"1096","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a)"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0993-7540","authenticated-orcid":false,"given":"Marco","family":"Stellato","sequence":"first","affiliation":[{"name":"Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-0226","authenticated-orcid":false,"given":"Sebastiano","family":"Buti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy"},{"name":"Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Maruzzo","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6527-6281","authenticated-orcid":false,"given":"Melissa","family":"Bersanelli","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8483-0196","authenticated-orcid":false,"given":"Francesco","family":"Pierantoni","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit 3, Department of Oncology, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-2908","authenticated-orcid":false,"given":"Ugo","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Di Napoli","sequence":"additional","affiliation":[{"name":"Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Iacovelli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-266X","authenticated-orcid":false,"given":"Maria Giuseppa","family":"Vitale","sequence":"additional","affiliation":[{"name":"Medical Oncology, University Hospital Modena, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ermacora","sequence":"additional","affiliation":[{"name":"Department of Oncology, University and General Hospital, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Malgeri","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione Policlinico Campus Bio-Medico, 00128 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5423-3158","authenticated-orcid":false,"given":"Brigida Anna","family":"Maiorano","sequence":"additional","affiliation":[{"name":"Oncology Unit, Foundation Casa Sollievo della Sofferenza IRCCS, 73013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Prati","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ospedale Michele e Pietro Ferrero, Verduno\u2014Azienda Sanitaria Locale CN2, Alba-Bra, 12060 Cuneo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3665-3295","authenticated-orcid":false,"given":"Alessia","family":"Mennitto","sequence":"additional","affiliation":[{"name":"SCDU Oncologia, \u201cMaggiore della Carit\u00e0\u201d University Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-3740","authenticated-orcid":false,"given":"Alessia","family":"Cavo","sequence":"additional","affiliation":[{"name":"SSD Oncologia Ospedale Villa Scassi, ASL 3 Genovese, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Santoni","sequence":"additional","affiliation":[{"name":"Oncology Unit, Macerata Hospital, 62100 Macerata, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Carella","sequence":"additional","affiliation":[{"name":"SSD Oncologia Medica, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Fratino","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology C, Centro di Riferimento Oncologico National Cancer Institute, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Verzoni","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"UOC of Medical Oncology, Sapienza Universit\u00e0 di Roma, Polo Pontino, 00196 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.eururo.2016.02.029","article-title":"The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs\u2014Part A: Renal, Penile, and Testicular Tumours","volume":"70","author":"Moch","year":"2016","journal-title":"Eur. 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