ESMO 2018: Nivolumab Alone or in Combination with Ipilimumab in Patients with Platinum-Pretreated Metastatic Urothelial Carcinoma, including the Expansion from CheckMate 032

Munich, Germany (UroToday.com) Jonathan E. Rosenberg, MD presented the preliminary results of the study analyzing the effects of Nivolumab alone or in combination with Ipilimumab in patients with platinum-pretreated metastatic urothelial carcinoma. This study is an expansion of the Checkmate 032 trial.

Dr. Rosenberg began with a short overview of the role of immunotherapy in metastatic urothelial carcinoma. Immunotherapy has recently become the recommended treatment for previously treated patients with metastatic urothelial carcinoma. Checkmate 032 is a multicenter, phase 1 and two studies which included three cohorts of patients with platinum-pretreated metastatic urothelial carcinoma:

  1. Nivolumab monotherapy at a dose 3 mg/kg (Nivo3)
  2. The combination of Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (Nivo3+IPI1)
  3. The combination of Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg (Nivo1+IPI3)
Among the 78 metastatic urothelial carcinoma patients previously treated with Nivolumab monotherapy, and the 104 patients who were previously treated with Nivo3+IPI1, an objective response rate of 26% and 38% was demonstrated, respectively. This presentation reports data of the follow-up study, including efficacy and safety outcomes in the expanded, additional Nivo1+IPI3 urothelial metastatic cohort. The study design is shown in figure 1. The primary endpoint included investigator-assessed objective response rate.

Patient demographic data showed that the median age in all three cohorts was 63-66, with the majority being males, and most patients having tumor PD-L1 expression <1%. Most patients have had at least two prior treatments, with approximately 20% of the patients having prior systemic neoadjuvant therapy and approximately 35% of patients undergoing adjuvant therapy. Lastly, ~85% of patients received some form of metastatic systemic therapy. The Nivolumab monotherapy, and the Nivo3 + IPI1 patients had a minimum follow-up of 37-38 months, while the recently added Nivo1+IPI3 arm had only 7.9 months of follow-up.

UroToday ESMO2018 Figure 1 Checkmate 032 study design png
Figure 1 – Checkmate 032 study design:

The results demonstrated an objective response rate of 25.6%, 26.9% and 38% for nivolumab monotherapy, Nivo3+IPI1, and Nivo1+IPI3, respectively.  Complete response rates and median time to response (months) were witnessed in 10.3% and two months, 7.7% and 1.4 months, and 6.5% and 1.4 months of the Nivolumab monotherapy, Nivo3+IPI1, and Nivo1+IPI3, respectively. The median progression-free survival was 2.8 months, 2.6 months, and 4.9 months in the nivolumab monotherapy, Nivol3+IPI1, and Nivo1+IPI3, respectively.  Similar differences were witnessed in the overall survival rates, with the nivolumab monotherapy, Nivo3+IPI1, and Nivo1+IPI3 demonstrating a median overall survival of 9.9, 7.4 and 15.3 months, respectively. In patients with PD-L1 expression of more than 1%, the objective response rate was higher in the Nivo1+IPI3 arm (58.1% vs. 23.8%)

Treatment-related adverse effects were quite similar between the groups, although slightly higher in the Nivo1+IPI3 group.

Dr. Rosenberg concluded his talk stating that with extended follow-up, Nivo3, Nivo3+IPI1, and Nivo1+IPI3 regimens demonstrated sustained efficacy in previously treated patients with metastatic urothelial carcinoma. The objective response rate was higher in patients with PD-L1 expression higher than 1% in the patients treated with Nivo1+IPI3 (58%).  A trend towards higher objective response rates and longer progression-free survival and overall survival was observed in the Nivo1+IPI3 arm. No new safety issues were identified with this longer follow-up. These results support the ongoing phase 3 trial of Nivo1+IPI3 vs. chemotherapy in previously untreated metastatic urothelial carcinoma patients, the Checkmate 901 study (NCT03036098).
 

Presented by: Jonathan E. Rosenberg, MD, Medical Oncologist, Chief, Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology; Enno W. Ercklentz Chair, New York, US

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, twitter: @GoldbergHanan at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23,  2018, Munich Germany

Further Related Content: Invited Discussant, Cora Sternberg, MD - Nivolumab Alone or in Combination with Ipilimumab in Patients with Platinum-Pretreated Metastatic Urothelial Carcinoma, from CheckMate 032
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