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:
- Nivolumab monotherapy at a dose 3 mg/kg (Nivo3)
- The combination of Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (Nivo3+IPI1)
- The combination of Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg (Nivo1+IPI3)
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.
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