ASCO GU 2018: Nivolumab Monotherapy in Metastatic Urothelial Carcinoma: Longer-term Efficacy and safety Results from the CheckMate 032 Study

San Francisco, CA (UroToday.com) Few options exist for patients who fail front-line platinum-based chemotherapy for metastatic urothelial carcinoma (UC). With the advent of immunomodulatory (IO) agents, this era is finally coming to an end. An important study in this space is the ongoing CheckMate 032 trial. This 3-arm trial is a nonrandomized study of treating platinum-resistant metastatic UC with: 1. Nivolumab-only; 2. Nivolumab + ipilimumab (1mg/kg); 3. Nivolumab + ipilimumab (3mg/kg).

Dr. Rosenberg, on behalf of the CheckMate investigators, presented longer-term 2-year data on the nivolumab-only arm of the study. The initial phase I/II report published in 2016 demonstrated a response rate (ORR) of 24% and 22% Grade 3-4 complications rate. 

Now, at 2-years of follow-up, the ORR% is 25.6%. Importantly, the study now has information on PD-L1 tumor expression levels (<1% vs. >1%). 53% of patients in the study had low levels of PD-L1 expression. Interestingly, the ORR% did not differ between the groups -- ~26% ORR% in both low- and high-PD-L1 expression groups.

The median time to response is 2 months, and duration of response was not reached at 2-year follow-up. Amazingly, 65% of patients who initially responded are still enjoying a durable response at 2 years. Looking at Kaplan-Meier progression and survival curves, there appear to be very few progression events after 1 year of therapy. This is mirrored by the overall survival (OS) data as well. The 1yr-OS was 46% and 2-yr OS was 37%. The median OS was 10 months. These types of durable responses are extremely rare in chemotherapy-only studies!

With regard to treatment-related adverse events (AEs), investigators reported 83% for all grades, and 28% for Grade 3-4 AEs. Only 3.8% of AEs led to treatment discontinuation. There was one death due to pneumonitis on study. 

In conclusion, there were no new safety signals or cause for concern with longer-term follow-up in the nivolumab-only arm of CheckMate 032. Responses remained around 25%, and those who respond tend to maintain that response by 2-year follow-up. These responses did not differ based on PD-L1 expression. These are extremely exciting data for patients with platinum-resistant metastatic UC. Follow-up from the nivolumab + ipilimumab arms are eagerly anticipated to see if these responses can be even better with combination IO therapy.

Presented by: Dr. Rosenberg on behalf of Dr. Padmanee Sharma

Written by: Shreyas Joshi, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA


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