THE COMBINATION of savolitinib and durvalumab achieved durable responses in approximately one-fourth of patients with metastatic papillary renal cell carcinoma in the phase II CALYPSO study.1
Treatment options are limited for papillary renal cell carcinoma. Clinical guidelines recommend enrollment into a clinical trial—the preferred strategy—or sunitinib. With these options, overall survival is approximately 12 months, and new treatments represent an unmet need.
Based on preliminary data suggesting synergy, savolitinib was combined with durvalumab for the phase II CALYPSO trial, a multiarm study that includes patients with different renal cell carcinoma histologies: clear-cell renal cell carcinoma, sarcomatoid, and papillary renal cell carcinoma.
In 41 evaluable patients, who were either vascular endothelial growth factor-treatment naive or refractory, 11 patients (27%) achieved response (all partial responses) on savolitinib/durvalumab. Fifteen patients (39%) achieved stable disease. Responses were similar in previously-treated patients.
A total of 22 of the 41 evaluable patients (54%) had a decrease in tumor burden. Of the 11 patients with objective response, an interim analysis showed a duration of response approaching 6 months. Three patients were not evaluable for response.
Cristina Suarez, MD, PhD
Cristina Suarez, MD, PhD, Vall d’Hebron University Hospital and Vall d’Hebron Cancer Institute, Barcelona, presented data at the 2019 Genitourinary Cancers Symposium based on a cohort of 42 patients with measurable metastatic papillary renal cell carcinoma. One patient experienced disease progression prior to study therapy.
Savolitinib monotherapy at 600 mg/d was administered during a 4-week lead-in period; then durvalumab at 1,500 mg was added. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate; secondary endpoints were progression-free survival, overall survival, duration of response, best response at 24 weeks, and safety.
Median age was 62 years and all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. A total of 29% of patients were good risk, according to International Renal Cell Carcinoma Database Consortium criteria, 63% were intermediate-risk, and 7% were poor-risk.
At a median follow-up of 6.9 months, in an interim analysis, the investigator-assessed median progression-free survival was 5.3 months and median overall survival was not reached. There was no correlation between PD-L1 status and MET biomarker expression with outcome.
The combination was tolerable; the most prominent all-grade adverse events were mostly grade 1 and 2 nausea, edema, and fatigue. The most frequent grade 3 adverse was edema, which occurred in 4 patients. One patient had a grade 4 toxicity (transaminitis); there were no grade 5 toxicities.
“The progression-free survival and overall survival are immature, but encouraging,” said Dr. Suarez. ■
DISCLOSURE: Dr. Suarez is a consultant/advisor with Bristol-Myers Squibb, Ipsen, Pfizer, and Sanofi; has received travel/accommodations/expenses from Bristol-Myers Squibb; and has other financial relationships with Astellas, Eisai, Exelixis, and Roche.
1. Powles T, Larkin JMG, Patel P, et al. A phase II study investigating the safety and efficacy of savolitinib and durvalumab in metastatic papillary renal cancer (CALYPSO). San Francisco: 2019 Genitourinary Cancers Symposium. Abstract 545. Presented February 16, 2019.