The study keynote-045 compared Pembrolizumab (PEMB) vs. chemotherapy in platinum refractory disease. Patients with MUC of upper and lower tract after 1-2 lines of platinum based chemotherapy or recurrence within 12 months of perioperative platinum based chemotherapy were included in the study. Patients were randomized to either PEMB or 2nd line chemotherapy. The study demonstrated a hazards ratio (HR) of 0.73 in favor of PEMB for OS. The IMVIGOR 211 study compared Atezolizumab (ATEZ) vs. 2nd line chemotherapy in platinum refractory PD-L1 positive metastatic disease. Results showed a HR of 0.87 (p=0.4) in favor of ATEZ, demonstrating the biomarker was prognostic but not predictive. Table 1 demonstrates key parameters of these 2 important studies.
Long term durable remission appears possible with all five PD/PD-L1 inhibitors shown in figure 1. All five agents should be considered as attractive alternatives to chemotherapy. PEMB is the only agent with statistically significant randomized phase 3 trial data supporting its use. So far, The PD-L1 biomarker has no role. It has also been shown that both carboplatin and ICI are reasonable choices for patients who are not eligible for cisplatin based chemotherapy.
In summary, there is increasing evidence of activity of ICI in bladder cancer. Currently, there are some signs of revival of targeted therapy.
Figure 1: Licensed immune check point inhibitors in metastatic urothelial cancer:
Table 1: Comparison of key parameters in the randomized phase 3 trials of Atezolizumab and Pembrolizumab:
Presented by: Thomas Powles, Barts cancer center
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, twitter: @GoldbergHanan at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark