ASCO GU 2019: Phase II Study of Ribociclib in Men with Unresectable, Incurable Teratoma with Recent Progression

San Francisco, CA (UroToday.com) Most patients with teratoma are managed by surgery and no standard medical therapy exists for progressive and unresectable teratoma. Little progress has been made in the treatment of progressive and unresectable disease, and no standard therapy exits. Teratomas have a functional expression of retinoblastoma protein, and clinical activity was observed with CDK4/6 inhibition.1 Ribociclib is an orally bioavailable small molecule inhibitor of CDK 4/6, approved for the use in patients with hormone receptor positive, human epidermal growth factor 2 negative advanced breast cancer. Given its mechanism of action, it may have potential therapeutic activity in patients with teratomas. 

In this trial, the authors report results from a randomized phase 2 study or Ribociclib compared with placebo in patients with unresectable and incurable teratomas with recent progression. 

The primary objective was to assess the efficacy of Ribociclib compared with placebo in patients with relapsed/refractory teratomas with recent progression. Secondary objectives included measures of efficacy, safety, and tolerability. This was a multicenter, double-blind study (primary treatment phase) and unblinded crossover treatment (secondary treatment phase), and post-treatment follow-up periods. 

The enrolled patients were older than 15 years with unresectable, progressive teratoma without malignant transformation, ECOG PS 0-1, and ≥ 1 line of prior chemotherapy. The primary endpoint was progression-free survival. Patients were randomized to receive RIBO (600 mg/day, three weeks on/1 week off) or placebo. 

The trial was closed early in the setting of slow accrual. Only ten patients were enrolled and received treatment before enrollment halt as shown in table 1. In the Ribociclib arm 6/8 patients discontinued treatment, 2 completed the primary treatwho arement and moved to the rollover trial to continue to receive Ribociclib. Demographic data are shown in table 2. The mean duration of exposure was significantly higher in the Ribociclib than in the placebo arm, as shown in table 3.

Table 1 - Patient Disposition
Phase II Study of Ribociclib in Men with Unresectable Incurable Teratoma with Recent Progression Table 1

Table 2 - Demographic and Disease Characteristics at Baseline 
Phase II Study of Ribociclib in Men with Unresectable Incurable Teratoma with Recent Progression Table 2

Table 3 - Duration of Exposure to Study Drug by Treatment 
Phase II Study of Ribociclib in Men with Unresectable Incurable Teratoma with Recent Progression Table3

Progression-free survival reached 71.4% in the Ribociclin arm and was maintained for 24 months. The remaining six patients were censored (Figure 1). At six months the progression-free survival was 50% in the placebo arm, reaching 0% by nine months. Summary of adverse events is demonstrated in table 3.

Figure 1- Kaplan-Meier Plot of Progression-Free Survival 
Phase II Study of Ribociclib in Men with Unresectable Incurable Teratoma with Recent Progression Figure1

Table 4 - Adverse Events Suspected to be Study Drug Related
Phase II Study of Ribociclib in Men with Unresectable Incurable Teratoma with Recent Progression Table4

In conclusion, this phase 2 study highlights the potential therapeutic activity of Ribociclib in patients with unresectable, incurable teratoma with recent progression. Progression-free survival was higher with Ribociclib and the treatment was well tolerated, and no new safety signals were identified.

Presented by: Daniel Castellano, MD, Hospital Universitario 12 de Octubre, Madrid, Spain

Reference: 
1. Vaughn DJ, et al. Cancer. 2015

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA