ESMO 2017: SPAZO2 (SOGUG): Comparative effectiveness of everolimus vs axitinib as second-line after first-line pazopanib in metastatic renal carcinoma

Madrid, Spain (UroToday.com) Dr. Jose Angel Arranz Arija and Spanish colleagues presented their results of everolimus vs axitinib as second-line therapy after first-line pazopanib for patients with metastatic renal cell carcinoma (mRCC) at today’s poster session at ESMO 2017. Pivotal studies assessing axitinib [1] and everolimus [2] in the second-line for mRCC did not include patients treated with first-line pazopanib. In addition, everolimus vs axitinib have not been directly compared in clinical trials in this setting. The authors aimed to compare the effectiveness of everolimus vs axitinib in real world clinical practice, as second-line after pazopanib in mRCC.

SPAZO2 was a retrospective real-world study to analyze the effectiveness of first-line pazopanib and subsequent therapies in mRCC in several settings in every day practice. Data from 530 patients treated with frontline pazopanib in 50 centers in Spain were collected by investigators. Out of 285 patients receiving 2nd-line targeted therapies after first-line pazopanib, 189 received either axitinib (n=88, 46.6%) or everolimus (n=101, 53.4%). There were no significant differences between the groups in terms of age (63 vs 66 years), gender (68% vs 64% males), prior nephrectomy (76% vs 67%), metastases to lymph nodes (58% vs 52%), liver (21% vs 28%), bone (45% vs 41%), CNS (6%), adrenal (4% vs 5%), pleura/peritoneum (4% vs 6%), or pancreas (4% vs 6%). Patients treated with everolimus were more likely to have non-clear cell histology (16 vs 1%) and skin/soft-tissue (28% vs 2%) metastases, whereas patients treated with axitinib were more likely to have lung (85% vs 72%) metastases. According to the IMDC risk stratification for second-line targeted therapies, 17% vs 9% of patients were favorable risk, 65% vs 69% were intermediate risk, and 18% vs 22% were poor risk for axitinib vs everolimus, respectively. Subsequent therapies were given in 56% for patients treated with axitinib vs 46% in for everolimus. Overall, after a median follow-up of 28 months, 74.6% of patients died, there was no complete responders, 11.2% had a partial response, and42.9% of patients had stable disease. The median PFS was 5 months (95%CI 4-6), and OS was 10.7 months (95%CI 8-13). There were no statistically significant differences between patients treated with axitinib vs everolimus in terms of ORR, PFS, and OS in the whole population or when stratified by IMDC risk groups.

The authors concluded that in this real-world study of patients with mRCC receiving second-line therapy after first-line pazopanib, there was no difference between second-line axitinib and everolimus across multiple endpoints. These results help to validate the use of both drugs in terms of clinical benefit, PFS and OS in the second-line setting.

Speaker: Jose Angel Arranz Arija, Hospital Gregorio Maranon Madrid, Madrid, Spain

Co-Authors: B. Pérez-Valderrama (Sevilla, Spain) A. Rodriguez Sanchez (Leon, Spain) J. Puertas Alvarez (Valladolid, Spain) A. Pinto Marin (Madrid, Spain) C. Maximiano Alonso (Majadahonda, Spain) J. Villa Guzman (Ciudad Real, Spain) E. Fernandez Parra (Sevilla, Spain) E. Gallardo Diaz (Sabadell, Spain) J. Gonzalez-Larriba (Madrid, Spain) J. Tafalla García (Madrid, Spain) J. Lambea (Zaragoza, Spain) M. Constenla Figueiras (Pontevedra, Spain) M. Mendez Vidal (Cordoba, Spain) J. Virizuela Echaburu (Sevilla, Spain) F. Vazquez Mazon (Elche, Spain) O. Etxaniz Ulazia (Badalona, Spain) M. Abad Villar (Bilbao, Spain) J. Cassinello (Guadalajara, Spain) J. Jurado García (Granada, Spain)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

References:

1. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised phase 3 trial. Lancet 2011;378(9807):1931-1939.
2. Motzer RJ, Barrios CH, Kim TM, et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 2014;32(25):2765-2772.