Pembrolizumab shows promise for some advanced, hard-to-treat rare cancers

March 19, 2020

HOUSTON -- A study conducted by researchers at The University of Texas MD Anderson Cancer Center demonstrated acceptable toxicity and anti-tumor activity in patients with four types of advanced, hard-to-treat rare cancers. Study findings were published in the March 17 online issue of the Journal for ImmunoTherapy of Cancer.

The open-label, Phase II study followed 127 patients who had advanced rare cancers: squamous cell carcinoma of the skin (cSCC), carcinoma of unknown primary (CUP), adrenocortical carcinoma (ACC), and paraganglioma-pheochromocytoma. Patients received 200 milligrams of the immunotherapy treatment pembrolizumab administered every three weeks between August 2016 and July 2018. All patients had tumors that had progressed on standard therapies.

"Our findings that pembrolizumab has a favorable toxicity profile and anti-tumor activity in patients with these rare cancers supports further evaluation in these populations," said Aung Naing, M.D., associate professor of Investigational Cancer Therapeutics. "Finding solutions for treatment is vital given that patients with advanced rare cancers have poor prognosis and few treatment options."

Rare cancers are defined by the American Cancer Society as those with an incidence of fewer than six cases per 100,000 people per year. CUP is a type of cancer in which the primary cancer site is not always known, but has spread to other areas within the body, while ACC occurs when malignant cells form in the outer layer of the adrenal glands. Paraganglioma-pheochromocytoma are tumors formed in nerve-like cells near the adrenal glands (pheochromocytomas) and near blood vessels or nerves in the head, neck, chest, abdomen, and pelvis. cSCC is the second most common type of skin cancer and is treatable in early stages, but harder to treat if in advanced stages.

The primary objective of the study was to find the proportion of patients who were alive and progression-free (non-progression rate) at 27 weeks on treatment with pembrolizumab. The median non-progression rate at that time was 28% for 127 patients with advanced rare cancers. Complete response, partial response or stable disease after four months was observed in 38% of the patients. Non-progression rates for each cancer group were: 36% for cSCC, 33% for CUP, 31% for ACC, and 43% for paraganglioma-pheochromocytoma. Treatment-related adverse events occurred in 52% of patients, with the most common side effects being fatigue and rash, with six deaths reported that were unrelated to treatment.

"Studies such as this one are key since rare cancers collectively accounted for 13% of all new cancer diagnoses and 25% of all cancer-related deaths in adults in 2017," said Naing. "The five-year survival rate is 15% to 20% lower than for more common cancers. The poor outcomes associated with rare cancers have been attributed to difficulty or delay in diagnosis, limited access to centers with expertise such as MD Anderson, and limited therapeutic options."

Naing added that, despite the significant burden and aggressive nature of these diseases, research that could lead to development and approval of new therapies are few. However, MD Anderson has the patient volume and research resources that uniquely positions its researchers to conduct this work.

"Findings from our study support further investigation to confirm the clinical activity of pembrolizumab in advanced rare cancers, and to identify immune signatures predictive of response to treatment,"said Naing.
MD Anderson study team participants included Funda Meric-Bernstam, M.D.; Bettzy Stephen, M.B.B.S.; Daniel Karp, M.D.; Jordi Rodon Ahnert, M.D.; Sarina Piha-Paul, M.D.; Saria Khan; Jeane Painter, Ph.D.; Abdulrahman Abonofal, M.D.; Jing Gong, M.D.; Anas Alshawa, M.D.; Lacey McQuinn; Mingxuan Xu, Ph.D.; Vivek Subbiah, M.D.; David Hong, M.D.; Shubham Pant, M.D.; Timothy Yap, M.D.; Apostolia Tsimberidou, M.D.; Ecaterina Ileana Dumbrava, M.D.; Filip Janku, M.D.; and Siqing Fu, M.D., all of the Department of Investigational Therapeutics; Rivka Colen, M.D.; and Sara Ahmed, M.D., of the Department of Cancer Systems Imaging; Camilo Jimenez, M.D.; and Mouhammed Habra, M.D., of the Department of Endocrine Neoplasia and Hormonal Disorders; Kanwal Raghav, M.D.; and Gauri Varadhachary, M.D., of the Department of Gastrointestinal Medical Oncology; Renata Ferrarotto, M.D., of the Department of Thoracic Head & Neck Medical Oncology; Shi-Ming Tu, M.D.; Matthew Campbell, M.D.; and Nizar Tannir, M.D., of the Department of Genitourinary Medical Oncology; Linghua Wang, Ph.D., of the Department of Genomic Medicine; Sharjeel Sabir, M.D., of the Department of Interventional Radiology; Coya Tapia, M.D., of the Department of Translational Molecular Pathology; Chantale Bernatchez, Ph.D., of the Department of Melanoma Medical Oncology; Michael Frumovitz, M.D., of the Department of Gynecologic Oncology and Reproductive Medicine; Vinod Ravi, M.D., of the Department of Sarcoma Medical Oncology; and Kenneth Hess, Ph.D., of the Department of Biostatistics.

Other participating institutions included Texas Children's Hospital and Baylor College of Medicine, Houston; and R. Simon Consulting, Potomac, Md.

Mercke Sharp &Dohme Corp, a subsidiary of Merck & Co., Inc.; the National Institutes of Health (P30CA016672) and MD Anderson's Molecular Evaluation and/or Biopsy Related Support Program funded the study. Naing reports research support and non-financial support from Mercke Sharp & Dohme Corp.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. The institution's sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 51 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is ranked No.1 for cancer care in U.S. News & World Report's "Best Hospitals" survey. It has ranked as one of the nation's top two hospitals for cancer care since the survey began in 1990, and has ranked first 15 times in the last 18 years. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).

University of Texas M. D. Anderson Cancer Center

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