Urologists! S1937 & S1931: Vital GU Studies

S1937: Eribulin, +/- gemcitabine, for patients with metastatic urothelial carcinoma

Urothelial carcinoma is the second most common GU cancer. It’s also the second most deadly.

A phase I/II study established eribulin’s activity in treating this disease, and a phase II study in the metastatic setting found giving the drug in combination with gemcitabine generated an objective response rate of 50 percent.

S1937 tests both solo eribulin and the eribulin—gemcitabine combo. It’s a phase III randomized three-arm trial in patients with metastatic urothelial carcinoma that has progressed on an immune checkpoint inhibitor or is deemed ineligible for a checkpoint inhibitor. It compares standard of care treatment for this disease (broadly defined) to treatment with eribulin given with or without gemcitabine.

Led by Drs. Sarmad Sadeghi and Primo Lara, the trial compares the two investigational arms to the control arm and to each other – is an eribulin—gemcitabine combination more effective than eribulin alone in these patients? The study is looking for a benefit in median overall survival of at least 50 percent over the standard of care arm. 

The randomization is 1:1:1 across the three arms, so patients should know they have a two out of three chance of getting an investigational treatment on the trial.

As there is no established standard treatment in this setting, standard of care for the control arm for S1937 is defined as any treatment endorsed for this setting in National Comprehensive Cancer Network (NCCN) guidelines. 

The accrual goal is 465 patients, and the study, which activated in early 2021, is now open at 365 sites nationwide.

The Norris Comprehensive Cancer Center at USC and the UC Davis Comprehensive Cancer Centerare tied as the lead enrollers to the study, but the Cancer Center at Saint Joseph’s in Phoenix (part of the CommonSpirit Health Research Institute) and Case Western Reserve University are close behind!

The study chairs have been working hard to make investigators aware of this trial and of why they should open and enroll to it, and Dr. Sadeghi presented an S1937 trials-in-progress poster at the ASCO GU Symposium last week.
 

S1931: Should patients on immunotherapy for metastatic RCC have surgery?

The second GU study I want to highlight is S1931, the PROBE trial, led by Drs. Hyung Kim and Ulka Vaishampayan, with Dr. Abhishek Tripathi as ECOG-ACRIN study champion. This study asks a seemingly straightforward question: should patients with metastatic renal cell carcinoma (RCC) being treated with immunotherapy have surgery to remove their kidney tumor?

The question may seem straightforward, but the answer to it is anything but.

Patients with metastatic RCC on S1931 get 10 – 12 weeks of initial combination therapy with an immune checkpoint inhibitor (the protocol lists several options for this combination). If their cancer responds to the treatment (or does not progress in that time), the patient is then randomized either to continued immunotherapy or to cytoreductive surgery followed by continued immunotherapy.

Patients can be registered to the trial either before they’ve begun immunotherapy or after a CT scan shows at least stable disease following their first 12 weeks of immunotherapy.

The study was activated at the end of 2020 and is now open for enrollment at 385 sites. The University of Michigan Comprehensive Cancer Center is the lead accruer to the trial, but the Tulane University Health Sciences Center is breathing down Michigan’s neck. Target accrual is 364 patients.

If you’re presenting this study to your patients, be sure to point them to the S1931 patient video as they consider whether to enroll. It’s a clearly delivered overview explaining the trial and the importance of its question.

Why do we need to answer this question? Dr. Mark Ball, of the NCI Urologic Oncology Branch stated it clearly at the recent ASCO GU Symposium in his presentation on the role of surgery in metastatic renal cell carcinoma:  there is no level 1 evidence to guide the role or sequence of surgery in the IO era.

S1931 PROBE will generate that evidence. Please enroll your patients to the study so we can provide a definitive answer. Thank you!