On June 2, 2017 Bristol-Myers Squibb Company (NYSE:BMY) reported the first disclosure of data from a cohort of the Phase 1/2 CheckMate -358 study evaluating Opdivo (nivolumab) for the treatment of patients with advanced cervical, vaginal and vulvar cancers, all associated with infection by the human papillomavirus (HPV) (Press release, Bristol-Myers Squibb, JUN 2, 2017, View Source [SID1234519342]). Schedule your 30 min Free 1stOncology Demo! The cohort included 24 patients, 19 of which were cervical cancer patients. The preliminary efficacy measures from the Phase 1/2 CheckMate -358 study (N=24) in patients with advanced cervical, vaginal and vulvar cancers, included an objective response rate (ORR), the primary endpoint, of 20.8% (95% CI: 7.1 to 42.2), with a 70.8% disease control rate of women experiencing complete or partial response or stable disease. The median progression-free survival (PFS) was 5.5 months (95% CI: 3.5 to not reached) and the median overall survival (OS) was not yet reached. Responses were seen only in cervical cancer patients. Of the 19 women with cervical cancer, five had complete and partial responses, with an ORR of 26.3% (95% CI: 9.1 to 51.2). Median duration of response has not been reached after 6 months of follow-up. Opdivo showed a safety profile consistent with previous results seen with Opdivo monotherapy in other tumor types. Grade 3/4 treatment-related adverse events (AEs) occurred in 12.5% of patients. These data will be presented today in an oral session at 4:12 to 4:24 PM CDT at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2017.
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"These CheckMate -358 results demonstrate the value of studying the potential of an Immuno-Oncology agent to address the significant challenge of treating patients with advanced cervical, vaginal and vulvar cancers," said lead investigator Antoine Hollebecque, M.D., senior medical physician, Gustave Roussy Cancer Institute in Villejuif, France. "As a clinical investigator, I am encouraged by these findings in the women with advanced cervical cancer, and look forward to the anticipated data from the planned longer term analyses."
HPV, which is transmitted through sexual contact, is linked with more than 90% of cervical cancers, about 75% of vaginal cancers and 69% of vulvar cancers. First-line treatment for women with advanced cervical cancer often consists of chemotherapy alone or combined with radiation, and the five-year survival rate for advanced cervical cancer, stages III and IV, ranges from about 35% to 16%.
"This first assessment of Opdivo’s activity in women with advanced cervical, vaginal and vulvar cancers enrolled in this cohort of CheckMate -358 supports further investigation, especially because these patients have very limited options after chemotherapy or radiation fails," said Shinta Cheng, M.D., Ph.D., development lead, Bristol-Myers Squibb. "These trial results also underscore our continued commitment to explore how Immuno-Oncology therapy might benefit as many appropriate patients as possible, including those with virally associated cancers of the gynecological system."
About CheckMate -358 (Abstract #5504)
CheckMate -358 is an ongoing Phase 1/2, open-label, international, multicenter, non-comparative, multi-cohort study that is evaluating the safety and efficacy of Opdivo monotherapy and Opdivo combination therapy in adult patients with virally associated tumors (Merkel cell carcinoma, gastric/gastroesophageal junction carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma of the head and neck, and squamous cell carcinoma of the cervix, vagina, vulva, anal canal and penis).
Patient tumor type, disease stage and resectability determined eligibility for enrollment in one of five treatment cohorts: neoadjuvant Opdivo monotherapy, metastatic Opdivo monotherapy, metastatic Opdivo combination therapy with Yervoy, metastatic Opdivo combination therapy with anti-LAG-3, or metastatic Opdivo combination therapy with daratumumab.
Patients in the neoadjuvant cohort received 2 doses of Opdivo 240 mg intravenously prior to scheduled surgery and patients in the monotherapy cohort were treated with Opdivo 240 mg intravenously every 2 weeks until unacceptable toxicity, withdrawal of consent or disease progression. The primary endpoints of the Phase 2 part of the study are objective response rate by investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria and safety. Secondary endpoints include progression-free survival overall survival, and duration of response.
About HPV & Cervical, Vaginal and Vulvar Cancers
In the majority of patients with human papillomavirus (HPV), which is transmitted through sexual contact, the immune system is effective at eliminating the initial infection. However, 10% to 15% establish life-long persistent infection, which may lead to virally mediated immune suppression and increased risk of cancers like cervical, vaginal and vulvar.
Worldwide, cervical cancer is the fourth most frequent cancer in women with an estimated 530,000 new cases in 2012 and is responsible for 7.5% of all female cancer deaths. Globally, more than an estimated one million women currently live with cervical cancer, as a consequence of a long-term HPV infection. Cancers of the vagina and vulva are rarer than cervical cancer, with estimated new annual diagnoses of 13,000 and 27,000 respectively, which represented 2% and 4% of all gynecological cancers in 2008.