Cabozantinib in metastatic renal cell carcinoma (mRCC): Data from UK expanded access program (EAP)

Background: Cabozantinib demonstrated increased efficacy over everolimus in patients with mRCC progressing on VEGF targeted therapy in the randomised phase III METEOR trial. We report real world experience with Cabozantinib in 7 centres across the UK. Methods: In this retrospective study, patients who started Cabozantinib from September 2016 to September 2017 within the UK EAP were included. Patients had mRCC progressing after at least 1 prior systemic treatment, PS 0-2 and adequate organ function. The goal was to analyse toxicities, efficacy and access to other drugs after progression. Adverse events (AEs) were graded using the NCI CTCAE v.4.0.3. Survival times were calculated from the start of Cabozantinib using a Kaplan-Meier model. Radiological response was assessed locally by RECIST 1.1. Results: 128 patients were included. Median follow-up was 10.5 months. Median age was 62 years, 84% had clear cell histology, and 49% were classified as intermediate risk by IMDC score. 87% had visceral M1 and 52% bone M1. Patients received a median of 2 previous lines (1-6) of therapy. Cabozantinib was used as 2nd line, 3rd line and 4th line or beyond in 56 (44%), 38 (30%) and 34 (26%) patients respectively. Baseline characteristics are summarized in the table. 48 (37%) of the patients developed G3/4 AEs, mainly fatigue (N = 14, 11%), diarrhoea (N = 12, 9%), mucositis (N = 7, 5%) and hand-foot syndrome (N = 6, 5%). No treatment-related deaths were seen. 71 patients (55%) required dose reductions. 12 (15%) discontinued Cabozantinib due to toxicity. Median OS was 9.1 months (95% CI 6.6-11.6), being 14.3 vs 9.3 vs 6.0 months for good, intermediate and poor prognostic patients, respectively (p 0.01). Median PFS was 7.7 months (95% CI 5.3-10.1). Partial response to Cabozantinib was 26%, stable disease 24%, Progressive disease 30% and was not evaluated in 20%. Only 21/81 patients (26%) stopping Cabozantinib started on subsequent treatment.Table: 893PBaseline characteristicNumber (%)GenderMale Female87 (68) 41 (32)AgeMedian (range)62 (11-83)PS ECOG0 1 220 (16) 85 (66) 23 (18)HistologyClear Cell Papillary Other107 (84) 13 (10) 8 (6)IMDC Risc CategoryGood Intermediate Poor Unknown35 (27) 62 (49) 27 (21) 4 (3)NephrectomyYes No93 (73) 35 (27)Number of metastatic sites1 2 ≥317 (13) 46 (36) 64 (50)Metastatic sitesLung Lymph node Bone Liver Brain Pleura/Peritoneal Other92 (72) 55 (43) 66 (52) 42 (33) 14 (11) 19 (15) 47 (37)Visceral and bone M1 spreadAll patients with visceral M1 Both Visceral + bone M1 Visceral M1 without bone M1110 (87) 55 (43) 54 (42)Previous lines of therapy1 2 ≥356 (44) 38 (30) 34 (26)Duration of 1st VEGFR TKI≤6 months >6 months34 (27) 94 (73)1st subsequent treatment (N = 21)Nivolumab Axitinib Everolimus Others15 (71) 3 (14) 1 (5) 2 (10)PD-1/PDL1 inhibitors prior to CaboNivolumab PD1/PDL1-VEGF combo27 (21) 10 (8) Open table in a new tab Conclusions: Cabozantinib was safe and active in pretreated patients with mRCC. Legal entity responsible for the study: Alfonso Gomez de Liano. Funding: Has not received any funding. Disclosure: S. Symeonides: Research funding: Merck Sharp & Dohme. T. Powles: Advisory role and research funding: Roche, AstraZeneca. All other authors have declared no conflicts of interest.