New treatment option for advanced urothelial cancer patients shows
promise in a phaseclinical trial

Date:
August 2, 2021
Source:
Weill Cornell Medicine
Summary:
A new treatment for advanced urothelial cancer was effective with
tolerable side effects in an international, multi-center phase 2
clinical trial. The trial results prompted a U.S. Food and Drug
Administration (FDA) accelerated approval of the treatment on
April 13, giving patients with this very aggressive type of cancer
a new therapeutic option.



FULL STORY ==========================================================================
A new treatment for advanced urothelial cancer was effective with
tolerable side effects in an international, multi-center phase 2
clinical trial led by investigators at Weill Cornell Medicine and NewYork-Presbyterian.


==========================================================================
The trial results prompted a U.S. Food and Drug Administration (FDA) accelerated approval of the treatment on April 13, giving patients with
this very aggressive type of cancer a new therapeutic option.

In the study, published online April 30 in the Journal of Clinical
Oncology, the researchers gave the treatment, sacituzumab govitecan
(SG), previously known as IMMU-132 and now by the trade name Trodelvy, to
113 patients with advanced urothelial carcinoma, the most common type of bladder cancer. The trial population had progressed despite treatment with platinum-based chemotherapy and immune-boosting "checkpoint inhibitors,
and overall had a median of 3 prior lines of therapy. Treatment with
SG was followed by sustained reductions in tumor size for 31 patients
(27 percent), including complete tumor disappearance in six patients. The
most common severe side effects included very low white blood cell count
in 34 percent (with fever in 10 percent) and severe diarrhea in 9 percent, which were managed with dose adjustment and best supportive care.

"The bottom line is that SG represents another option for patients with
this aggressive type and stage of cancer -- and it's also nice that it
has a different target and mechanism of action compared to other drugs
for this indication," said lead principal investigator of the global
trial Dr. Scott Tagawa, a professor of medicine in the Division of
Hematology and Oncology at Weill Cornell Medicine and medical director
of the genitourinary oncology program at NewYork-Presbyterian/Weill
Cornell Medical Center.

Urothelial carcinoma accounts for about 90 percent of bladder cancers and occurs at a rate of about 70,000 new cases and 17,000 deaths per year in
the United States. More than three quarters of these cases are in men,
and cigarette smoking increases the risk of this cancer by several times.

Advanced urothelial carcinoma, in which the tumor is inoperable or has metastasized, is normally treated with platinum-based chemotherapy drugs,
such as cisplatin or carboplatin, and/or immune checkpoint inhibitor drugs
that aim to unleash the immune system's anticancer capabilities. But in
most cases, those treatments work for a limited period of time before
the disease progresses again.



========================================================================== Sacituzumab govitecan is an antibody-drug conjugate. The drug portion,
a chemotherapy agent called SN-38, is attached to an antibody that homes
in on a receptor called Trop-2 -- found on most urothelial carcinoma
cells. In this way the drug can aim to specifically kill tumor cells
while largely sparing healthy cells.

The company that makes SG was testing it mainly against other cancers,
but Dr.

Tagawa, who is also a professor of urology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and his colleagues
showed in a 2015 pilot trial that it shrank tumors in three of six
patients with advanced urothelial carcinoma that had not responded to platinum-based chemotherapy. That trial led to the enrollment of a group
of 45 patients with treatment-refractory urothelial carcinoma (amongst
many others with various advanced cancers) with encouraging results.

In the new phase 2 trial, called TROPHY-U-01 and sponsored by Gilead
Sciences, they tested SG in 113 patients with advanced urothelial
carcinoma whose cancers had progressed despite platinum and checkpoint inhibitor treatment. The patients, treated at 42 sites around the world, including NewYork-Presbyterian/ Weill Cornell Medical Center and Seattle
Cancer Care Alliance, one of the higher accruing sites, received infusions
of SG twice every three weeks.

Treatment was stopped if tumors grew (progressed) or the side effects
became unacceptable.

An independent, blinded analysis of tumor scans revealed shrinkage of
tumors in 76 percent of the patients, and an "objective response,"
meaning significant, sustained tumor shrinkage, in 27percent of the
patients -- including the disappearance of tumors in six patients. The
median duration of response was 7.2 months, and the median overall
survival from start of treatment was 10.9 months.

By contrast, standard cytotoxic chemotherapy for treatment-resistant
advanced urothelial cancer in this category has an objective response rate
of about 10 percent, with median overall survival of about seven months.

As the TROPHY-U-01 study was ongoing, another antibody-drug conjugate
called enfortumab vedotin (EV) was granted accelerated approval by the
FDA, with recently published phase 3 trial data that are likely to lead
to full approval, according to Dr. Tagawa. The number of patients in the TROPHY-U-01 trial who had been treated with EV was small but showed a
similar response compared with the rest of the trial participants. This
finding was not surprising given that each therapy has a different target
and linker and uses a different toxin to destroy tumors, he said.

Dr. Tagawa cautions that the TROPHY-U-01 trial was a preliminary one
that lacked a concurrent control group -- every patient was treated --
and thus it is hard to compare its results to those for other drugs. He
notes, though, that the maker of SG, late last year, began a randomized, controlled, phase 3 trial of the drug comparing it to chemotherapy (TROPiCS-04). The results from that study, due in another few years,
will determine whether the FDA grants full regulatory approval.

"In the meantime, thanks to our study, this treatment will continue to be available to at least some of our patients with bladder cancer," said Dr.

Tagawa.

========================================================================== Story Source: Materials provided by Weill_Cornell_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Scott T. Tagawa, Arjun V. Balar, Daniel P. Petrylak, Arash Rezazadeh
Kalebasty, Yohann Loriot, Aude Fle'chon, Rohit K. Jain, Neeraj
Agarwal, Manojkumar Bupathi, Philippe Barthelemy, Philippe
Beuzeboc, Phillip Palmbos, Christos E. Kyriakopoulos, Damien
Pouessel, Cora N. Sternberg, Quan Hong, Trishna Goswami, Loretta
M. Itri, Petros Grivas. TROPHY-U-01: A Phase II Open-Label Study
of Sacituzumab Govitecan in Patients With Metastatic Urothelial
Carcinoma Progressing After Platinum-Based Chemotherapy and
Checkpoint Inhibitors. Journal of Clinical Oncology, 2021; 39
(22): 2474 DOI: 10.1200/JCO.20.03489 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210802160627.htm

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