Source: curetoday.com<\/p>\n
Women with endometrial cancer that is not categorized as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who are not eligible for curative surgery or radiation, and whose disease has progressed after previous systemic therapy now have a new, and much needed, treatment option.
Last week, the Food and Drug Administration (FDA) approved the combination use of Lenvima (lenvatinib) and Keytruda (pembrolizumab) for this patient population.
\u201cWhile the majority of endometrial cancer is early stage and potentially curable, metastatic recurrent endometrial cancer rarely is. Our treatment options for women with advanced and recurrent endometrial cancer are limited by a \u2018shallow bench\u2019 of treatment options,\u201d Dr. Amelia Jernigan, a gynecologic oncologist with the LSU Health Sciences Center Department of Obstetrics and Gynecology, explained in an interview with\u00a0CURE<\/em>.
Therapeutic Need<\/strong>
While many women will respond initially to front-line chemotherapy (about 50% to 60%), Jernigan noted that these responses are rarely durable and eventual recurrence or progression through treatment is the rule. In addition, second-line treatments have been shown to induce a much lower response rate (about 14% to 16%).
\u201cAs endometrial cancer is the most common gynecologic cancer in the US, we often find ourselves trying to figure out what to do after front-line therapy fails,\u201d she added.
In addition, there is a need for treatment of women whose tumors are not categorized as MSI-H or dMMR \u2013 features of cancer\u2019s genetic coding, which result in it behaving and \u201clooking\u201d a certain way on a microscopic level.
\u201cMSI-H or dMMR tumors are tumors that have broken cellular machinery to fix mismatches in the DNA of a cell and the presence of this can be tested on tumor specimens,\u201d said Jernigan, who is also an active member of the Society of Gynecologic Oncology and serves on the Communications Committee.
However, 70% of women\u2019s endometrial cancers are not MSI-H or dMMR. \u201cTherefore, most women in desperate need of a promising second-line therapy were still at a loss,\u201d she said.
KEYNOTE-146 Trial<\/strong>
The FDA based its decision on data from the multi-cohort, multicenter, open-label, single-arm phase 2 KEYNOTE-146\/Study 111 trial \u2013 designed to evaluate Keytruda in combination with Lenvima among 108 patients with metastatic endometrial carcinoma that had progressed following at least one prior systemic therapy in any setting. In particular, the agency focused on data from 94 patients in the study whose tumors were not MSI-H or dMMR.
A little over one-third of whom had a response to the regimen that lasted up to six months.
\u201cThe nearly 40% response rate in all comers in this trial is exciting because it allows for women who fail front-line chemotherapy to have a higher chance of responding to treatment,\u201d Jernigan said.
Project Orbis<\/strong>
The FDA\u2019s decision was also made under a new initiative of the FDA Oncology Center of Excellence, known as\u00a0Project Orbis, which is designed to allow international partners to concurrently submit oncology drugs for review. In addition to the FDA, the Australian Therapeutic Goods Administration and Health Canada collaborated on the review of the combination, leading to simultaneous approvals in all three countries.
\u201cWith attempts to maximize safety, understand value and efficacy of new drugs, and variable administrative processes for new drug approval from country to country, patients can often experience considerable delays in access to novel and cutting-edge cancer treatments due to regulatory hold up,\u201d Jernigan explained, adding that because of this, Project Orbis seems to be a success.
As part of the initiative, the agency was able to approve the novel combination three months ahead of the\u00a0Prescription Drug User Fee Act\u00a0date.
\u201cThe hope is to maintain a safe and thorough approval process but cut through some of the red tape and cut out some of the inefficiency,\u201d Jernigan said. \u201cThis will hopefully minimize the number of patients who do not get access to the latest cancer treatment options because of regulatory hold up.\u201d
Moving Forward<\/strong>
Moving forward, Jernigan sees the oncology field embracing more targeted therapies like the combination use of Keytruda and Lenvima. With this, the goal is also to aim for an increased use of targeted treatment options with improved toxicity and more durable responses for women with endometrial cancer.
\u201cEndometrial cancer represents a diverse group of cancers and we\u2019ve embraced carboplatin and paclitaxel as front-line therapy for advanced and recurrent disease. However, in select patient populations, we\u2019ve found that using a targeted therapy either alone or in combination with systemic chemotherapy can improve outcomes,\u201d she added. \u201cI think we will begin to be able to more specifically identify targets that are actionable in this diverse group of tumors.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":1875,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[1902,311,1901,273,53,113],"class_list":["post-1874","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-fda-2","tag-cancer","tag-endometrial","tag-health","tag-treatment","tag-women"],"yoast_head":"\n