ASCO GU 2018: Renal Cell Carcinoma Primary Tumor Shrinkage on Vascular Endothelial Growth Factor Targeted Therapy - A Pooled Analysis

San Francisco, CA (UroToday.com) Cytoreductive nephrectomy (CRN) is an important treatment modality in patients with advanced renal cell carcinoma (RCC), however the role and timing in the context of vascular endothelial growth factor (VEGF) - targeted therapy (TT) remains under investigation. The aim of this study was to determine the efficacy of VEGF-TT to induce primary tumor shrinkage in advanced RCC.

Methods:

The authors conducted a pooled analysis of 12 Pfizer-sponsored trials in patients with metastatic RCC treated with sunitinib, sorafenib, axitinib, bevacizumab, termsirolimus or interferon-α. Primary endpoint was the primary tumor objective response rate (ORR) by RECIST in patients who have not undergone prior nephrectomy. Kaplan-Meier method was used to estimate median overall survival (OS) of responders (partial or complete) vs. non-responders. Cox regression adjusting for demographics, histology type, prior therapy, metastasis sites, IMDC risk factors and neutrophil-to-lymphocyte ratio was used to compare OS between pts with and without primary tumor ORR.

Results:

565/4736 patients (12%) included in this study had their primary tumors intact, of which 360 (8%) received VEGF-TT. In patients with primary tumor intact, 87% had clear-cell RCC and IMDC risk group were 4% favorable, 33% intermediate, 39% poor, 24% unknown. 35% had bone metastasis and 32% had liver metastases. 65% had ECOG performance status ≥1. Compared to patients with prior nephrectomy, primary tumor intact patients were more likely to have bone or liver metastases or to be IMDC poor risk. Primary tumor ORR was 17% (95% exact CI, 14, 20) in all patients, 19% (95% CI. 16, 23) in first line treated patients and 23% (95% Exact CI, 19, 28) in patients treated with VEGF-TT (any line). Primary tumor ORR was 20% (95% CI. 15, 26) in IMDC intermediate risk pts and 9% (95% exact CI. 5 – 13) in the poor risk. Median OS was 33.98 months in patients with primary tumor ORR and 9.8 months in patients without ORR, adjusted HR 0.42 [95%CI, 0.28, 0.6; p < 0.0001].

Conclusions:

VEGF-TT lead to primary tumor shrinkage in 23% of patients with IMDC intermediate and poor risk advanced RCC, who have not undergone CRN. VEGF-TT may potentially facilitate future CRN in select patients. 


Presented by: Dominick Bosse, MD Boston, MA, USA

Co Authors: Xun Lin, Ronit Simantov, Aly-Khan A. Lalani, Ithaar Derweesh, Steven Lee Chang, Toni K. Choueiri, Rana R. McKay; Dana-Farber Cancer Institute, Boston, MA; Pfizer Oncology Inc., San Diego, CA; Pfizer Oncology Inc., New York, NY; University of California San Diego, San Diego, CA; Brigham and Women's Hospital, Boston, MA; Dana-Farber Cancer Institute/ Brigham and Women’s Hospital/Harvard Medical School, Boston, MA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA