Nav: Home

Targeted therapy erdafitinib effective for patients with advanced bladder cancer and specific gene mutations

July 24, 2019

Treatment with the FGFR inhibitor erdafitinib in patients with metastatic bladder cancers marked by mutations in the FGFR3 gene resulted in a 40% overall response rate (ORR) and was well-tolerated, according to an international Phase II trial led by The University of Texas MD Anderson Cancer Center.

The trial results, published today in the New England Journal of Medicine, led to approval of erdafitinib in April by the Food and Drug Administration (FDA), making it the first targeted therapy approved for treating patients with advanced bladder cancer.

The oral targeted therapy also achieved a 59% ORR in patients for whom immunotherapy had previously failed, indicating this may be a viable option for these patients in need of alternative treatments. The findings were first reported at the 2018 American Society of Clinical Oncology Annual Meeting by principal investigator Arlene Siefker-Radtke, M.D., professor of Genitourinary Medical Oncology.

"Patients have been in desperate need for alternative strategies, especially when a large number of patients cannot tolerate the current standards of care," said Siefker-Radtke. "We were very gratified to see a 40% response rate in patients treated on this clinical trial. Not only did it work well in patients with lymph node metastases, but also in patients with high volume and very aggressive disease."

Standard of care for these cancers is cisplatin-based chemotherapy, an aggressive regimen with significant side effects, and this has largely remained unchanged for several decades, explained Siefker-Radtke. Recently, immune checkpoint inhibitors have been approved for the treatment of advanced bladder cancer, but only 15 to 20% of patients see any benefit from these therapies, she said.

"I noticed that I wasn't seeing a great response to immune checkpoint inhibitors in my patients with FGFR3 mutations, which led me to wonder whether this would reflect a group of patients with an unmet need," said Siefker-Radtke. "When we heard about novel agents targeting this pathway, I became quite interested in exploring them in our bladder cancer patients."

Mutations in FGFR3 are present in approximately 15 to 20% of patients with metastatic bladder cancer and up to 35% of patients with other urothelial cancers, such as those of the renal pelvis and ureter. The international trial enrolled 99 patients with metastatic or surgically unresectable urothelial cancer and verified alterations in the FGFR3 gene.

Three patients in the trial had complete responses, or tumor disappearance, and 39 had percent stable disease. Median PFS was 5.5 months and median OS was 13.8 months. Among 22 patients previously treated with immunotherapy, 59% (13) had a partial or complete response.

"With a response rate of over 50% in patients previously treated with immunotherapy, the data suggest treatment with erdafitinib may be preferential for patients with FGFR3 mutations. However, this is preliminary evidence, so we need additional data to confirm this finding," said Siefker-Radtke.

All patients on the trial reported side effects from the therapy, with 21% discontinuing treatment due to adverse events and 67% reporting grade 3 or 4 adverse events. The most common treatment-related side effects were stomatitis (9%), nail dystrophy (6%), and hand-foot syndrome (5%).

Based on the results of the trial, the FDA granted a breakthrough therapy designation to erdafitinib in 2018 and approved the drug in April 2019 for treating patients with locally advanced or metastatic urothelial cancers with mutations in the FGFR2 or FGFR3 genes.

"With the recent approval of erdafitinib for the treatment of patients with FGFR3-mutant urothelial cancers, we now have an additional agent to add to our armamentarium," said Siefker-Radtke. "My hope is we will be able to add this to our treatment strategy, learn how it combines with immunotherapy and how we can use the effects of this drug to improve the survival for all of our bladder cancer patients."

A Phase III trial currently is underway to evaluate the efficacy of erdafitinib relative to chemotherapy or the checkpoint blockade inhibitor pembrolizumab in patients with metastatic urothelial cancer and FGFR3 mutations.
-end-
The study was funded by Janssen Research & Development, LLC. Siefker-Radtke serves on the scientific advisory committee for Janssen. A full list of collaborating researchers and their disclosures are included in the paper.

University of Texas M. D. Anderson Cancer Center

Related Immunotherapy Articles:

Transition to exhaustion: clues for cancer immunotherapy
Emory research on immune cells 'exhausted' by chronic viral infection provides clues on how to refine cancer immunotherapy.
Using artificial intelligence to determine whether immunotherapy is working
Currently, only about 20% of all cancer patients will actually benefit from costly immunotherapy.
Clues to improve cancer immunotherapy revealed
A new study by researchers at Washington University School of Medicine in St.
Algorithm personalizes which cancer mutations are best targets for immunotherapy
As tumor cells multiply, they often spawn tens of thousands of genetic mutations.
Tasmanian devil research could help tackle immunotherapy resistance
A cluster of interacting proteins that are active in both human cancers and Tasmanian devil facial tumours, may give clues to how cancers evade the immune system, according to a study part-funded by Cancer Research UK and published in Cancer Cell today (Thursday).
B cells linked to immunotherapy for melanoma
Immunotherapy uses our body's own immune system to fight cancer.
Delivering immunotherapy directly to brain tumors
A new study published this week gives insight into how cancer immunotherapies might one day be delivered directly to the brain in order to treat brain tumors.
Researchers discover a new form of immunotherapy
A new form of immunotherapy that has so far been tested on mice makes it probable, that oncologists in the future may be able to treat some of the patients who are not responding to existing types of immunotherapy.
Better tools, better cancer immunotherapy
Researchers from DTU have developed an important new tool towards producing therapies for cancer patients using the patient's own cells.
Immunotherapy and diabetes: A game of hide and seek?
Immune checkpoint inhibitors (ICIs) are emerging as an effective treatment for certain cancers, but in rare cases can cause autoimmune diseases.
More Immunotherapy News and Immunotherapy Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab