Everolimus or sunitinib as first-line treatment of metastatic papillary renal cell carcinoma: A retrospective study of the GETUG group (Groupe d'Etude des Tumeurs Uro-Genitales)

Mathilde Cancel (1) , Gaelle Fromont (2) , Cyriac Blonz (3) , Christine Chevreau (4) , Nathalie Rioux-Leclercq (5) , Brigitte Laguerre (6, 7) , Stéphane Oudard (8) , Marine Gross-Goupil (9) , Gwenaëlle Gravis (10, 11) , François Goldwasser (12, 13) , Frédéric Rolland (3) , Rémy Delva (3) , Laura Moise (14) , Sheik Emambux (15) , Cécile Vassal (16) , Sylvie Zanetta (17) , Nicolas Penel (18, 19, 20) , Aude Fléchon (21) , Philippe Barthélémy (22) , Félix Lefort , Carolina Saldana (23, 24) , Bernard Escudier , Claude Linassier , Laurence Albiges

1 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
2 Service d'Anatomopathologie [Tours]
3 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
4 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
5 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
6 Département d'oncologie médicale [Rennes]
7 CRLCC - CRLCC Eugène Marquis
8 HEGP - Hôpital Européen Georges Pompidou [APHP]
9 Hôpital Saint-André
10 CRCM - Centre de Recherche en Cancérologie de Marseille
11 IPC - Institut Paoli-Calmettes
12 Hôpital Cochin [AP-HP]
13 PRETRRAM (URP_4466) - Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme
14 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
15 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
16 Institut de Cancérologie Lucien Neuwirth
17 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
18 UNICANCER/Lille - Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille]
19 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
20 EA 2694 - Santé Publique : épidémiologie et qualité des soins
21 Département cancer environnement (Centre Léon Bérard - Lyon)
22 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
23 CHU Henri Mondor [Créteil]
24 TRePCa - Résistances Thérapeutiques du Cancer de la Prostate

Background: Two phase II trials (NCT00688753 and NCT00541008) reported efficacy data of sunitinib and everolimus in first-line treatment of metastatic papillary renal cell carcinoma (mpRCC). Although most patients receive sunitinib or a mammalian target of rapamycin (mTOR) inhibitor in first-and second-line treatment, the optimal strategy remained unknown. Material and methods: In 23 centres of the Groupe d'Etude des Tumeurs Urogenitales group, after centralised pathological review, we analysed retrospectively progression-free survival (PFS) of patients with mpRCC treated in first-line treatment (PFS-1) with sunitinib or everolimus (primary end-point), PFS in second-line treatment (PFS-2), overall survival (OS), objective response rate, disease control rate (DCR), overall sequence and prognostic factors for OS (secondary end-points). Results: One hundred thirty-eight patients (119 men and 19 women), median age 62.5 years, with mpRCC type 1 (n = 24) or non-type 1 (n = 114), received first-line sunitinib (n = 107) or everolimus (n = 31). With a median follow-up of 92 months, we found no significant difference between the treatment groups in terms of PFS-1 (5.5 versus 6.2 months) and DCR (69% versus 83%). Ninety-eight patients received a second-line treatment, 69% with mTOR inhibitors after sunitinib and 100% with tyrosine kinase inhibitors after everolimus, with similar DCR (64% versus 58%), median PFS-2 (3.4 versus 4.8 months) and OS (16.0 versus 20.3 months). No factor was prognostic for PFS-1, whereas leukocytosis, anaemia and the time from diagnosis to first systemic therapy < 1 year were prognostic for OS. We found no prognostic difference between both pRCC subtypes. The International Metastatic Renal Cell Database Consortium risk factors were prognostic for OS. Conclusion: Sunitinib and everolimus had similar efficacy in first-line treatment of patients with mpRCC. 2021 Elsevier Ltd. All rights reserved.

Mots clés: Papillary renal cell carcinoma; Metastatic; Sunitinib; Everolimus; First-line treatment; Prognostic factors; Real world; IMDC risk groups

Domaines: Cancer

Mathilde Cancel, Gaelle Fromont, Cyriac Blonz, Christine Chevreau, Nathalie Rioux-Leclercq, et al.. Everolimus or sunitinib as first-line treatment of metastatic papillary renal cell carcinoma: A retrospective study of the GETUG group (Groupe d'Etude des Tumeurs Uro-Genitales). European Journal of Cancer, 2021, 158, pp.1-11. ⟨10.1016/j.ejca.2021.08.046⟩. ⟨hal-04242387⟩