She kicked off the session by reviewing the numerical burden of metastatic urothelial cancer reviewing the recent numbers and trends. Specifically, she notes that bladder cancer is primarily diagnosed in the localized setting. However, survival for patients with distant metastatic disease remains extremely poor. Interestingly, it is projected that by 2040 in the United States there will be 10,000 fewer deaths from bladder cancer. This is not to be the impact of immune-oncology medications and antibody-drug conjugates. However, she knows the concern that these benefits are likely to be seen in high-income countries that have modern but “financially toxic” treatment approved. The rest of the world might not see this benefit.
Immune checkpoint blockade for bladder cancer starts in the metastatic urothelial carcinoma setting. In 2014, Tom Powles presented data on MPDL3280A at ASCO.1 This has kicked off the IO storm that followed. That study demonstrated a 50% objective response rate (ORR) with durable responses. Importantly, there were 2 complete responses (CRs) in the responsive group, which was not previously seen.
Her next slide highlights the progression from cisplatin-failure to cisplatin-ineligible first-line therapy to now 2020 first-line triplet therapy trials.
However, she notes that more is not always better! Also in 2020, JAVELIN Bladder 100 was presented, demonstrating the benefit of switch maintenance therapy after platinum-based therapy.2 Based on this data, the guidelines for metastatic urothelial carcinoma were changed to strongly recommend maintenance avelumab.
She did note that DANUBE and KEYNOTE-361 both did not meet primary endpoints, but there were other important IO studies presented in 2020/2021. These were both first-line triplet therapy options.
The current EAU guidelines have been modified in March 2021 to incorporate these changes.
The current use of IO drugs in metastatic urothelial carcinoma is for:
1) Platinum-eligible patients – as maintenance therapy after CR/PR/SD
2) Platinum-ineligible patients – PD-L1+
3) 2nd line after platinum failure
She did highlight that there are numerous ongoing phase 3 trials that will likely change this landscape further.
Presented by: Ursula Vogl, MD, Senior Consultant, Medical Oncology at Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
References:
1. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014 Nov 27;515(7528):558-62. doi: 10.1038/nature13904. PMID: 25428503.
2. Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18. PMID: 32945632.