Clinical Benefit of Everolimus as Second-Line Therapy in Metastatic Renal Cell Carcinoma: The French Retrospective SECTOR Study

Stéphane Oudard (1, 2, 3) , Florence Joly (4, 5) , Lionnel Geoffrois (6) , Brigitte Laguerre (7) , Nadine Houédé (8, 9) , Philippe Barthélémy (10) , Marine Gross-Goupil (11) , Yann A Vano (1, 2, 3) , Oliver Lucidarme (12) , François Bidault (13) , Nadia Kelkouli (14) , Khemaies Slimane (14) , Bernard Escudier (15)

1 Service d'oncologie médicale [CHU HEGP]
2 UPD5 - Université Paris Descartes - Paris 5
3 HEGP - Hôpital Européen Georges Pompidou [APHP]
4 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
5 Cancers et préventions
6 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
7 Département d'oncologie médicale [Rennes]
8 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
9 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
10 Département d'Oncologie et Hématologie [Strasbourg]
11 CHU Bordeaux
12 CHU Pitié-Salpêtrière [AP-HP]
13 Département de médecine oncologique [Gustave Roussy]
14 Novartis Pharma S.A.S.
15 Oncologie génito-urinaire

BACKGROUND: Real-world data of everolimus after vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy in metastatic renal cell carcinoma (mRCC) are limited. PATIENTS AND METHODS: The retrospective, noninterventional SECTOR (SECond line with afiniTOR) study (N = 165) assessed outcomes of second-line everolimus after initial VEGFR-TKI (TKI-everolimus, n = 144) and of third-line VEGFR-TKI after everolimus (TKI-everolimus-TKI, n = 59) in patients with mRCC. The primary end point was duration of everolimus therapy for both populations. RESULTS: Median duration was 4.0 months (range, 0.0-33.0 months) for second-line everolimus and 18.0 months (range, 2-78 months) for sequential VEGFR-TKI and everolimus. Median overall survival (OS) for this sequence was 36.0 months (95% confidence interval [CI], 27.0-56.0 months) and was longer for patients who received a first-line TKI for ≥ 9 months (not reached) than for < 9 months (28.0 months; P < .001). During second-line everolimus treatment, commonly reported adverse events (all grades) were fatigue (n = 66, 40.7%), anemia (n = 58, 35.8%), and stomatitis (n = 41, 25.3%). Median duration from initiation of first-line TKI to the end of the third-line TKI was 24.0 months (95% CI, 19.0-29.0 months). Median OS for this sequence was 41.0 months (95% CI, 25.0-57.0 months) and was significantly longer for patients who received the first-line TKI for ≥ 9 months (37.5 months) than for < 9 months (19.0 months; P < .0001). CONCLUSION: These results reflect clinical use of sequential TKI-everolimus and TKI-everolimus-TKI and provide additional evidence that everolimus could be an option in second-line therapy in mRCC. Results of the CheckMate-025 (Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma) and METEOR (Metastatic RCC Phase 3 Study Evaluating Cabozantinib versus Everolimus) studies might change the treatment landscape.

Mots clés: VEGFR inhibitor; Sequential targeted therapy; mTOR inhibitor; Observational study; Real-world study

Domaines: Urologie et Néphrologie; Cancer

Stéphane Oudard, Florence Joly, Lionnel Geoffrois, Brigitte Laguerre, Nadine Houédé, et al.. Clinical Benefit of Everolimus as Second-Line Therapy in Metastatic Renal Cell Carcinoma: The French Retrospective SECTOR Study. Clinical Genitourinary Cancer, 2016, 14 (6), pp.e595 - e607. ⟨10.1016/j.clgc.2016.04.019⟩. ⟨hal-01904931⟩