{"id":18269,"date":"2020-01-14T12:00:00","date_gmt":"2020-01-14T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2020\/enfortumab-vedotin-bladder-cancer-fda-approval"},"modified":"2024-11-03T15:16:51","modified_gmt":"2024-11-03T15:16:51","slug":"enfortumab-vedotin-approved-for-recurrent-bladder-cancer","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/enfortumab-vedotin-approved-for-recurrent-bladder-cancer\/","title":{"rendered":"Enfortumab Vedotin Approved for Recurrent Bladder Cancer"},"content":{"rendered":"
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The antibody component of enfortumab vedotin binds to the nectin-4 protein on bladder cancer cells. Once enfortumab enters the cell, the MMAE is released and causes the cell to die.<\/p>\n

Credit: Used with permission from Seattle Genetics<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

On December 18, 2019, the Food and Drug Administration (FDA) granted accelerated approval to enfortumab vedotin<\/a>-ejfv (Padcev) for people with advanced bladder cancer that has progressed despite treatment with two previous therapies.<\/p>\n

Enfortumab vedotin was the second targeted drug to be approved for the treatment of advanced bladder cancer in 2019. Earlier in the year, FDA granted accelerated approval to erdafitinib (Balversa)<\/a>. However, erdafitnib can only be used to treat cancers that have an alteration in one of several genes called FGFR<\/em>. Only about 20% of bladder cancers harbor an FGFR<\/em> alteration.<\/p>\n

\u201cWe have been desperately looking for a new treatment option for patients\u201d with advanced, progressive disease<\/a>, said Joaquim Bellmunt, M.D., Ph.D., who directs the Bladder Cancer Program at Beth Israel Deaconess Medical Center in Boston.<\/p>\n

The approval of enfortumab vedotin was based on findings from a cohort of participants in a small clinical trial called EV-201<\/a> that enrolled people with metastatic bladder cancer. All 125 participants in the cohort had been treated with chemotherapy that used platinum-containing drugs (such as cisplatin<\/a> and oxaliplatin<\/a>) as their initial, or first-line, treatment. When their cancer progressed, an immune checkpoint inhibitor<\/a> had been used as their second-line treatment.\u00a0<\/p>\n

All patients in the trial received enfortumab vedotin. Overall, 55 participants (44%) had their cancers shrink or stop growing during treatment<\/a>. Fifteen of these had their tumors disappear entirely, known as a complete response<\/a>. Responses to treatment lasted for a median<\/a> of 7.6 months. The trial was funded by the drug\u2019s manufacturers, Seattle Genetics and Astellas Pharma.<\/p>\n

Currently, the standard third-line treatment for people with metastatic bladder cancer is chemotherapy that uses taxane<\/a> agents, such as paclitaxel<\/a> and docetaxel<\/a>.\u00a0<\/p>\n

\u201cAnd less than 10% of our patients actually have responses to these regimens,\u201d said Tian Zhang, M.D., of Duke University, who is involved with another ongoing study of enfortumab vedotin. \u201cWe’ve seen some great responses [with enfortumab vedotin], and I’m really hopeful for a lot of my patients who might benefit from this drug.\u201d<\/p>\n

A Common Target<\/h2>\n

Enfortumab vedotin is a type of targeted therapy<\/a> called an antibody\u2012drug conjugate. Antibody\u2012drug conjugates consist of a monoclonal antibody<\/a> chemically linked to a drug.\u00a0<\/p>\n

The monoclonal antibody part of enfortumab vedotin binds to a protein called nectin-4, which is found on the surface of most bladder cancer cells. The antibody is chemically linked to monomethyl auristatin E, or MMAE, a type of chemotherapy drug called a microtubule<\/a> inhibitor. Once the conjugate is taken up by cells, the drug stops them from dividing and leads to their death.<\/p>\n

Because nectin-4 is present on the majority of bladder cancers, it’s not necessary to have a diagnostic test to determine which patients are eligible for treatment, explained Dr. Bellmunt.\u00a0<\/p>\n

The participants enrolled in EV-201 received infusions of the drug about 3 times a month until disease progression or unacceptable side effects occurred, or if they chose to leave the study for any reason.\u00a0<\/p>\n

The most common side effects included fatigue, hair loss, decreased appetite, changes in the ability to taste, and peripheral neuropathy<\/a>. Febrile neutropenia<\/a>\u2014fever and a reduced number of white blood cells\u2014was the most common serious side effect related to treatment.<\/p>\n

Treatment-related rash also occurred in about half of participants but was usually mild.<\/p>\n

Overall, side effects led 32% of patients to receive a lower dose of enfortumab vedotin and 12% to discontinue treatment. Peripheral neuropathy was the most common cause of dose reduction or treatment discontinuation.<\/p>\n

At the time the trial\u2019s preliminary results were published, almost half of the 55 patients who had had a response to the drug still hadn\u2019t experienced progression of their cancer. Responses lasted from about 3 months to more than 11 months.\u00a0<\/p>\n

Though the trial is still ongoing, the researchers estimated that the median progression-free survival<\/a>\u00a0was 5.8 months, and the median overall survival<\/a> was 11.7 months.<\/p>\n

More to Study<\/h2>\n

Under an accelerated approval, a drug\u2019s manufacturer must further study and verify a treatment\u2019s clinical benefit. An ongoing<\/a> phase 3 clinical trial<\/a> is comparing enfortumab vedotin with taxane-based chemotherapy as third-line treatment.<\/p>\n

There are currently unanswered questions about which third-line drug should be given first to people with FGFR-positive bladder cancer, who would also be eligible to receive erdafitinib.<\/p>\n

\u201cWe don’t know if the order [of these drugs] matters. There’s no clinical trial or data [yet],\u201d explained Dr. Bellmunt.<\/p>\n

And because treatment response rates in the EV-201 trial were so high\u2014comparable to what\u2019s normally seen with first-line therapy\u2014researchers are beginning to test enfortumab vedotin earlier in treatment, Dr. Zhang said.\u00a0<\/p>\n

For example, an ongoing trial<\/a> is testing enfortumab vedotin alone and in combination with immunotherapy, chemotherapy, or both as an initial treatment for people with advanced bladder cancer.<\/p>\n

Preliminary results from one arm of that trial were presented in September 2019 at the European Society for Medical Oncology\u2019s annual meeting. That data showed response rates of around 70%<\/a> with the combination of enfortumab vedotin and the immune checkpoint inhibitor pembrolizumab (Keytruda)<\/a> in patients who were too sick to receive platinum-based chemotherapy. Such a response rate<\/a> is \u201cphenomenal\u201d for people with metastatic bladder cancer, explained Dr. Zhang.<\/p>\n

\u201cThe concept is really to try to bring active treatments earlier in the disease process,\u201d Dr. Zhang said. \u00a0\u201cWe want to [learn] more about enfortumab vedotin, potentially even for [treating] localized disease.\u201d\u00a0<\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

January 14, 2020, by NCI Staff The antibody component of enfortumab vedotin binds to the nectin-4 protein on bladder cancer cells. Once enfortumab enters the cell, the MMAE is released and causes the cell to die. Credit: Used with permission from Seattle Genetics On December 18, 2019, the Food and Drug Administration (FDA) granted accelerated […]<\/p>\n","protected":false},"author":2,"featured_media":18270,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-18269","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/18269","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=18269"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/18269\/revisions"}],"predecessor-version":[{"id":44355,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/18269\/revisions\/44355"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/18270"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=18269"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=18269"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=18269"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}