{"id":6512,"date":"2018-07-26T16:00:00","date_gmt":"2018-07-26T16:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2018\/bladder-cancer-checkpoint-inhibitor-change"},"modified":"2024-11-03T15:17:33","modified_gmt":"2024-11-03T15:17:33","slug":"fda-alters-approved-use-of-two-checkpoint-inhibitors-for-bladder-cancer","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/fda-alters-approved-use-of-two-checkpoint-inhibitors-for-bladder-cancer\/","title":{"rendered":"FDA Alters Approved Use of Two Checkpoint Inhibitors for Bladder Cancer"},"content":{"rendered":"

July 26, 2018, by NCI Staff<\/p>\n

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Several drugs that target immune checkpoint proteins like PD-1 and PD-L1 are approved to treat bladder cancer. Credit:\u00a0<\/span>Adapted from<\/span>\u00a0<\/span>Onco Targets Ther April 2017. doi: 10.2147\/OTT.S133385 CC BY 3.0.<\/span><\/p>\n<\/div>\n<\/figcaption><\/figure>\n

The Food and Drug Administration (FDA) has changed the approved uses of two immunotherapy drugs to treat people with the most common form of bladder cancer, urothelial carcinoma.<\/p>\n

Last year, the drugs\u2014pembrolizumab (Keytruda)<\/a> and atezolizumab (Tecentriq)<\/a>\u2014received approval<\/a> for the treatment of patients with previously untreated urothelial carcinoma that has spread beyond the bladder. The 2017 approvals covered the use of the drugs for patients who, because of other health-related factors, cannot receive the chemotherapy drug cisplatin, which is a standard treatment for patients with advanced bladder cancer.<\/p>\n

Approximately half of people diagnosed with bladder cancer that has spread can\u2019t receive cisplatin, explained Andrea B. Apolo, M.D., of the Genitourinary Malignancies Branch (GMB) in NCI\u2019s Center for Cancer Research<\/a>.<\/p>\n

Last year\u2019s approvals were based on results from two small, early-phase clinical trials. On June 20, however, the agency announced that data from two larger, ongoing clinical trials showed that patients with metastatic bladder cancer treated with either pembrolizumab or atezolizumab died sooner than those treated with a standard chemotherapy regimen.<\/p>\n

The worse survival was seen specifically in people whose tumor cells had very low levels of the protein PD-L1.<\/p>\n

As a result of the new findings, FDA announced that it was changing the prescribing label for both drugs. Under the change, pembrolizumab and atezolizumab should be used as an initial, or first-line, treatment in only those people with metastatic bladder cancer who can\u2019t receive cisplatin-based chemotherapy and whose tumors have high levels of PD-L1. The assessment of PD-L1 levels must be made using an FDA-cleared test.<\/p>\n

Under the labeling change, Dr. Apolo noted, patients who can\u2019t be treated with any platinum-containing\u00a0therapy can still receive either immunotherapy drug, regardless of their PD-L1 levels.<\/p>\n

Following Up on Accelerated Approvals<\/h2>\n

Pembrolizumab and atezolizumab are both immune checkpoint inhibitors, and both are approved by FDA to treat patients with metastatic bladder cancer that has continued to progress on standard treatments such as combinations of chemotherapy drugs.<\/p>\n

The expanded approvals of both drugs as first-line treatments in 2017 were accelerated approvals, based on the findings from smaller clinical trials showing that some patients\u2019 tumors shrank following treatment. Because they were not randomized<\/a> trials that compared the drugs against standard treatments, however, the trials could not show whether patients who received the immunotherapy drugs lived longer.<\/p>\n

Under an accelerated approval, a drug\u2019s manufacturer has to conduct a larger trial to confirm that the drug does indeed have a meaningful benefit for patients, such as improving survival or quality of life.<\/p>\n

It was the early\u00a0analyses of data from two of these confirmatory trials\u2014KEYNOTE-361<\/a> (pembrolizumab) and IMvigor 130<\/a> (atezolizumab)\u2014which showed that patients with low PD-L1 levels who received the checkpoint inhibitor alone \u201chad decreased survival compared to patients who received cisplatin- or carboplatin-based chemotherapy,\u201d the agency reported.<\/p>\n

PD-L1 levels have been widely studied as a biomarker<\/a> for response to treatment with checkpoint inhibitors. PD-L1 on tumor cells is involved in dialing down the immune response<\/a>, and both pembrolizumab and atezolizumab disrupt that process. Several checkpoint inhibitor approvals have been limited to people whose tumors have elevated PD-L1 levels.<\/p>\n

However, using PD-L1 levels to select treatment for these patients \u201cputs oncologist in the difficult position of finding a laboratory that will do the correct assay for that specific therapy,\u201d said Dr. Apolo.\u00a0 \u201cThe assays used with atezolizumab and pembrolizumab each look at different cells, the cut-off for a \u2018positive\u2019 result is still being fine-tuned for each assay, and some patients may not have tissue available for testing,\u201d she explained.<\/p>\n

Also, for patients who are ineligible to receive cisplatin, selecting treatment based on the PD-L1 levels of their tumors \u201cmay eliminate a viable, effective treatment option for some patients,\u201d said Dr. Apolo. \u201cBased on the reported studies that led to these approvals, approximately 20%\u201330% of cisplatin-ineligible bladder cancer patients with low PD-L1 levels had durable responses to atezolizumab or pembrolizumab.\u201d<\/p>\n

According to FDA, patients with low PD-L1 levels are no longer being enrolled in the KEYNOTE-361 or IMvigor 130 trials.<\/p>\n

Evolving Role of Immunotherapy in Bladder Cancer<\/h2>\n

It\u2019s not surprising that the patients who received chemotherapy responded well to treatment, said Dr. Apolo, who heads the GMB\u2019s Bladder Cancer Section. \u201cChemotherapy is very active in patients with urothelial carcinoma,\u201d she explained.<\/p>\n

In fact, Dr. Apolo continued, evidence from previous bladder cancer trials has shown that the rates at which patients\u2019 tumors shrink after treatment with first-line chemotherapy regimens that include cisplatin or carboplatin are higher than the rate for cisplatin-ineligible patients treated with a first-line checkpoint inhibitor.<\/p>\n

However, patients whose tumors do respond to checkpoint inhibitors tend to maintain those responses for long periods, she said. So the premise in these trials was that these extended responses \u201cwould translate into a survival benefit.\u201d<\/p>\n

Data on whether survival will be improved for patients with high PD-L1 levels treated with only a checkpoint inhibitor are still not available. In addition, KEYNOTE-361 and IMvigor 130 also have a treatment group that is receiving the immunotherapy drug in combination with chemotherapy, but efficacy data are not yet available for those groups either.<\/p>\n

Dr. Apolo stressed that, in patients whose cancer has progressed after chemotherapy treatment, \u201cimmunotherapy with checkpoint inhibitors [alone]\u00a0is still the standard of care.\u201d<\/p>\n

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

July 26, 2018, by NCI Staff Several drugs that target immune checkpoint proteins like PD-1 and PD-L1 are approved to treat bladder cancer. Credit:\u00a0Adapted from\u00a0Onco Targets Ther April 2017. doi: 10.2147\/OTT.S133385 CC BY 3.0. The Food and Drug Administration (FDA) has changed the approved uses of two immunotherapy drugs to treat people with the most […]<\/p>\n","protected":false},"author":2,"featured_media":6513,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-6512","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\/6512","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=6512"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/6512\/revisions"}],"predecessor-version":[{"id":42829,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/6512\/revisions\/42829"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/6513"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=6512"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=6512"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=6512"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}