ASCO 2019: Urothelial and Variant Cases: Medical Oncologist Perspective

Chicago, IL (UroToday.com) Evan Yu, MD, focused his presentation at ASCO 2019 on cisplatin-ineligible patients with urothelial carcinoma.

What is cisplatin-ineligibility? Work by Galsky et al. defines cis-ineligible as the following1:

ASCO2019_Galsky_et_al.png

We know from multiple studies and level 1 evidence that cisplatin combination therapy is the standard. There are 2 regimens often used in urothelial carcinoma – MVAC and gemcitabine-cisplatin. Data from multiple groups have demonstrated that gem-cis is non-inferior to MVAC – but all of these have also shown that “other regimens,” often carboplatin-based regimens, are significantly worse than cisplatin combination regimens:

ASCO2019_MVAC.png

Based on this, all major national and international guidelines recommend against neoadjuvant therapy if patients are cisplatin ineligible. Many specifically state that carboplatin should not be substituted in this setting.

However, Dr. Yu notes that there are ongoing trials and work looking at novel therapies that may eventually become the standard of care. He specifically highlighted the PURE-01 and ABACUS trials. In the PURE-01 trial, in which pembrolizumab was utilized in the neoadjuvant setting for cis-eligible patients, they found a 42% pT0 rate at the time of RC and a 51% rate of downstaging. The ABACUS trial, which assessed atezolizumab in the cis-ineligible population, the authors identified a 29% pT0 CR response. These, along with the upcoming neoadjuvant trials in cis-ineligible patients, are likely to change the landscape in the near future.

ASCO2019_ABACUS.png

In the adjuvant setting, for patients who develop metastatic disease following primary definitive therapy, the options for cis-ineligible patients are broader:

  • Gemcitabine with carboplatin – this can be considered in this setting. It is likely not as effective but may be enough in some patients.
  • Pembrolizumab or Atezolizumab (Atezo) – these are newer agents that have been FDA-approved in this setting. However, they have multiple other considerations prior to use.
  • Gemcitabine/Carboplatin (Gem/Carbo) with either Pembrolizumab or Atezolizumab – there is work being done with combination, but it is not ready for actual use yet.
Gem/Carbo, in this setting, has the best ORR amongst 2nd line chemotherapy regimens – ORR 36%, time to progression is 4.8 months, and overall survival (OS) 7.2 months. In comparison, the results from ImVigor 210 (Atezo) demonstrated a 24% objective response rate (ORR), 2.7 progression free survival (PFS) and 14.8 month OS. In the Keynote 052 study (Pembro), ORR was 29%, 2.3 month PFS, and 11.5 month OS. So, while ORR was a bit lower, they had good survival outcomes – and this may be due to the nature of “response” in immune checkpoint inhibitors. Even stable disease may respond well with the use of ICIs.

There are also more drugs expected to enter this field as the following trials finish, including a combination of ICI’s:

ASCO2019_ongoing_trials.png

Presented by: Evan Y. Yu, MD, Professor, Department of Medical Oncology, University of Washington School of Medicine, Seattle, WA

Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @JEFFUrology, at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References: 
  1. Galsky et al. (JCO 2017)
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