ESMO 2018: Efficacy and Safety Results of GETUG, Axitinib in Metastatic Papillary Renal Cancer

Munich, Germany (UroToday.com) Papillary renal cell carcinoma (pRCC) is a rare form of RCC, which represents 15-20% of renal epithelial tumors1. There is limited data on the best sequence of therapies for papillary RCCs. The largest randomized trial for pRCC was the ASPEN trial, which randomized 108 patients to either sunitinib or everolimus2. In this study, patients treated with sunitinib had a longer median progression-free survival with sunitinib than everolimus (8.1 vs 5.5 months). However, for patients with poor risk disease, there was a signal that everolimus may be a better option than sunitinib. MET inhibitors such as crizotinib, foretinib, and savolitinib have also been explored in small phase II studies. Savolitnib demonstrated a response rate of 18% (8/44) with a median PFS of 6 months for tumors which were MET “driven”, as defined as a chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations3. The results of this study have prompted a phase III clinical trial comparing savolitinib with sunitinib for MET driven tumors (NCT03091192).

This abstract describes the efficacy of frontline axitinib for the treatment of papillary RCC. The primary endpoint was 24-week progress free rate. Secondary objectives included safety, progression-free survival, overall survival, and best response rate.

56 patients were enrolled and underwent a central pathology review. This is important as 5 patients were discovered to not have papillary RCC. The discussant notes that it is critical to have critical pathology review of papillary RCC cases because misclassification is not uncommon.  Of the 50 remaining cases, 13 were Type 1 and 30 were Type 2, and ultimately 44 were given therapy.

Most patients were men (84%) and the median age was 75. All had a performance status of 0 or 1 and the majority had intermediate or poor IMDC prognosis. 84% of patients had prior nephrectomy.

ESMO 2018 patient characteristics

In terms of efficacy, 26% of patients had a partial response, 64% of patients had stable disease, and 9.5% of patients had progressive disease.  Median PFS was 23.8 weeks for all patients and numerically similar for papillary type 1 and papillary type 2 (21.0 and 23.8 months). Median overall survival was 18.9 months for all patients and has not been reached for papillary type 1 patients.

ESMO 2018 efficacy

In terms of toxicity, 15.9% percent of patients had treatment discontinuation due to SAEs. There were no unexpected toxicities. The most common grade 3/4 SAEs were hypertension, GI symptoms, and deterioration in performance status.

ESMO 2018 toxicity

In this study, axitinib demonstrated substantial disease control for patients with papillary RCC and has a median PFS similar to other therapies for this indication.

ESMO 2018 trials in mPRC

Given the rarity of papillary RCCs, it is important for patients with pRCC be enrolled in clinical trials so that we can develop strategies to best target this challenging disease.  One such study is PAPMET, which is randomizing patients to one of four treatment arms: sunitinib, cabozantinib, crizotinib, and volitinib (NCT02761057). There are several targeted therapy studies and immunotherapy studies ongoing, which will be critical for developing the treatment paradigm for pRCC. Per the discussant, MET status should be determined for all patients with papillary RCC, and if MET positive, consideration should be given to MET inhibitors. If MET status is unknown or wildtype, then sunitinib and axitinib should be considered.

ESMO 2018 personal view

ESMO 2018 targeted therapies

ESMO 2018 ongoing trials immunotherapy


Presented By: Sylvie Negrier, MD, PhD, Centre Leon Berard, Lyon, France

Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23,  2018, Munich Germany


References:

1. Allory Y, Ouazana D, Boucher E, Thiounn N, Vieillefond A. Papillary renal cell carcinoma. Virchows Archiv 2003;442:336-42.
2. Armstrong AJ, Halabi S, Eisen T, et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. The Lancet Oncology 2016;17:378-88.
3. Choueiri TK, Plimack ER, Arkenau H-T, et al. A single-arm biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer (PRCC). American Society of Clinical Oncology; 2017.H-TChoueiri TK, Plimack ER, Arkenau H-T, et al. A single-arm biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer (PRCC). American Society of Clinical Oncology; 2017.savolitinibChoueiri TK, Plimack ER, Arkenau H-T, et al. A single-arm biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer (PRCC). American Society of Clinical Oncology; 2017.
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