Pembrolizumab Immunotherapy Benefits Some Merkel Cell Carcinoma Patients

MedicalResearch.com Interview with:

Paul Nghiem, MD, PhD Professor & Head, University of Washington Dermatology George F. Odland Endowed Chair Affiliate Investigator, Fred Hutchinson Cancer Research Center Professor, Adjunct, of Pathology and Oral Health Sciences Clinical Director, Skin Oncology, Seattle Cancer Care Alliance UW Medical Center at Lake Union Seattle WA 98109

Dr. Paul Nghiem

Paul Nghiem, MD, PhD
Professor & Head, University of Washington Dermatology
George F. Odland Endowed Chair
Affiliate Investigator, Fred Hutchinson Cancer Research Center
Professor, Adjunct, of Pathology and Oral Health Sciences
Clinical Director, Skin Oncology, Seattle Cancer Care Alliance
UW Medical Center at Lake Union
Seattle WA 98109

 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Nghiem: Merkel cell carcinoma (MCC) is about 30 times less common than malignant melanoma, but about 3 times more likely to kill a patient than a melanoma. There is no FDA-approved therapy for this cancer & chemotherapy typically only provides about 90 days prior to the cancer progressing. Because of the strong links between MCC and the immune system, including the fact that most MCCs are caused by a virus, there was interest in trying to use immune checkpoint therapy to treat advanced Merkel cell carcinoma. The response to immune stimulation with anti-PD1 therapy was about as frequent as to chemotherapy (56% of patients responded) but importantly, among the responders, 86% remained in ongoing responses at a median of 7.6 months.  While still early, this appears to be strikingly more durable than responses to chemotherapy.

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Immunotherapy Drug Nivolumab May Help Some Aggressive HPV-Induced Anal Cancers

MedicalResearch.com Interview with:

Dr. Van K. Morris, MD Assistant Professor, GI Medical Oncology The University of Texas MD Anderson Cancer Center

Dr. Van Morris

Dr. Van K. Morris, MD
Assistant Professor, GI Medical Oncology
The University of Texas MD Anderson Cancer Center

MedicalResearch.com: What is the background for this study?

Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past.

Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer.

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Study Reveals High Rate of Anal Cancer in HIV-Positive Women

Newswise — NEW YORK CITY (April 12, 2012) — Anal cancer is on the rise among HIV-positive women, according to a Montefiore Medical Center study entitled, “High Prevalence of High Grade Anal Intraepithelial Neoplasia in HIV-Infected Women Screened for Anal Cancer,” to be published in the Journal of Aids on May 1.

“Anal cancer was widely associated with HIV-infected men who have sex with men,” said Mark H. Einstein, MD, MS, Director of Clinical Research, Division of Gynecologic Oncology at Montefiore Medical Center and Professor at Albert Einstein College of Medicine. “But now, this study reveals anal precancerous disease in a high proportion of women with HIV.”

Out of 715 asymptomatic HIV-infected women studied, 10.5% exhibited some form of anal disease and approximately one third of them were found to be true pre-cancerous disease. The researchers determined that this is likely due to the fact that HIV promotes human papillomavirus (HPV) persistence and consequently, which is known to cause nearly all anal cancers. HIV-infected individuals are also at increased risk for the development of many other HPV-associated neoplasms.

The incidence of anal carcinoma (AC) has been increasing despite the implementation of antiretroviral therapy (ART), which has not been shown to consistently alter the course of HPV–associated anogenital disease.

The women studied were Montefiore patients in the Bronx, which has one of the highest HIV prevalence rates in the United States. Data indicates that 1.8% of the Bronx population is known to be HIV infected, representing 3% of the total number of HIV patients in the entire country. Montefiore is the largest provider of medical services for people with HIV in the Bronx and has adopted routine screening for AC with annual anal cytology in all HIV-infected patients.

As a result of these findings, Dr. Einstein and his colleagues recommend that all HIV+ women who have any abnormal anal cytology be referred for high resolution anoscopy, particularly those with poorly controlled HIV who are significantly at even higher risk for harboring a high-grade AIN than women who are well controlled. Also, all HIV infected men and women should be considered for anal cancer screening. Given the lower high-grade anal disease prevalence in women with well-controlled HIV, other strategies to improve disease ascertainment, such as inclusion of HPV testing might be found to be useful for AC screening. This risk stratification might prove to be different for women than it is for men, where prevalence rates seem to be considerably higher. Given the high rate of high-grade anal precancerous lesions in screened HIV-infected women and an aging population of HIV-infected patients, measures to increase routine AC screening should be strongly considered. Depending on the size of the pre-cancerous legion, it can be removed long before it becomes cancer, thus being able to save lives.