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 ( 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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