FDA Approval Withdrawal of Trodelvy Leaves Fewer Bladder Cancer Options

With the recent decision to rescind the Food and Drug Administration (FDA) approval of Trodelvy (sacituzumab govitecan-hziy) for the treatment of certain patients with bladder cancer, there is now one less treatment option available for patients and providers, as one expert explained.

“The most important thing is that one of the options we had some optimism for as another available systemic therapy for urothelial cancers, for the time being, is not going to be an option,” Dr. John L. Gore told CURE® in an interview.

Gore, a member of CURE’s advisory board, is an oncologist at the University of Washington Medical Center and Fred Hutchinson Cancer Center, the University of Washington’s Jessie H. Bridges Endowed Professor in Prostate Cancer and Urology Research, a University of Washington associate professor of urology and a professor of surgery.

Last month, manufacturer Gilead Sciences announced the voluntary withdrawal of the FDA’s accelerated approval of Trodelvy for the treatment of locally advanced or metastatic urothelial cancer, a type of bladder cancer, that has been previously treated with platinum-containing chemotherapy and a PD-(L)1 inhibitor.

The FDA’s accelerated approval for Trodelvy in metastatic urothelial cancer was granted in 2021 based on findings from the phase 2 TROPHY-U-01 study, with continued approval contingent on findings from the TROPICS-04 study, Gilead explained in a news release. However, TROPICS-04 did not reach its primary end point of overall survival, the news release stated.

“What's really important to understand is that, in their study, the reason why they pulled the drug is because overall survival was not better in the patients that got the Trodelvy,” Gore said. “That doesn't mean that no one benefited. And so sometimes, when this happens, we learn different biomarkers of response that help us understand, well, gosh, maybe this drug isn't for everybody, but for those that have this biomarker or that biomarker, it is helpful. And so that's a common sort of next step when the main study didn't show an overall benefit.”

Trodelvy is a type of drug known as an antibody-drug conjugate, otherwise described as a form of “targeted chemotherapy” by Dr. Yousef Zakharia, co-leader of the Genitourinary Oncology Program at the University of Iowa, to CURE® earlier this year.

“It is an antibody that is directed toward certain receptors on the cancer cells. … And basically, this antibody is attached to a payload, which is a very effective chemotherapy,” he said. “The way it works [is that] it takes that chemotherapy, carries it directly to the cancer cells, and it gets internalized within the cancer cells. That payload or chemotherapy gets integrated within the microtubules and starts disrupting the cell growth, and that results in cell killing. In other words, it is carrying the cytotoxic material directly and specifically to the cancer cells with the hope to save the normal cells from the toxic [adverse] effects associated with that if they do not have that specific receptor expressed.”

The approval withdrawal, Gilead noted, does not affect Trodelvy’s other FDA approvals for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one of them for metastatic disease, and for unresectable locally advanced or metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.

“It's important to know [that] even though the receptor that this is active against is common across a number of cancers, it doesn't mean it has the same activity across a number of cancers,” Gore said. “[Although] it maybe didn't work as well as we’d hoped in bladder cancer doesn't mean the same is true of breast cancer, just like just because it worked well in breast cancer doesn't mean it's automatically going to work in bladder cancer. That's why we need to do these clinical trials; we need to understand what works and what doesn't in a really controlled setting.”

In the news release, Gilead stated that patients who are being treated with Trodelvy for metastatic urothelial cancer in the United States should discuss their care with their provider.

“The first thing they should do is reach out to their provider if they're on this drug, and ask if they should continue taking it, or if they should potentially switch to another therapy,” Gore said. “A lot of it depends on the response. If they're doing well and they're having a good response to the medication, it would be hard for a provider to take them off of it, especially because the main use for this drug is in a in a down-the-line setting where other medications haven't worked as well as we'd hoped, or they worked initially, and then the tumor got worse. So if it's working, I think most providers would be hard pressed to stop it, even with this news.”

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