Investigational immunotherapy drug well tolerated in those with rare form of melanoma

Immunotherapies harness the body's natural defenders, T-cells, in fighting a disease like cancer. T-cells can be looked at as a car that crashes into cancer cells. PD-L1 is a brake on the car that prevents it from crashing. The immunotherapy drug avelumab examined in this study allows that brake to be released, allowing T-cells to do their job in attacking the disease -- in this case, Merkel cell carcinoma.

Merkel cell carcinoma is a sun exposure-related form of skin cancer that is more aggressive than melanoma affecting 1,500 people each year in the United States and according to the National Cancer Institute, the number of cases diagnosed each year is on the rise. The five-year survival rate for this disease is approximately 60 percent and is only 20 percent for those with disease that has spread to other parts of the body (metastatic). "Chemotherapy and radiation are not associated with long-term, overall survival, and this form of cancer is uniformly fatal, especially for those with metastatic disease. With that, there is clearly an unmet need for treatment options in this population," says the study's lead investigator Howard L. Kaufman, MD, FACS, associate director for clinical science and chief surgical officer at Rutgers Cancer Institute of New Jersey. Dr. Kaufman and colleagues examined patients with metastatic disease.

The study enrolled 88 patients, whose metastatic Merkel cell carcinoma progressed after receiving first or second line chemotherapy. Participants received a 10 mg/kg dose of avelumab every two weeks. Participants were followed for a median of 10 months. Investigators found 32 percent of patients achieved a complete or partial response (eight complete, 20 partial) and another 10 percent (nine patients) achieved stable disease. The findings also showed tumor responses to be rapid, with 22 of 28 patients (78.6 percent) responding to avelumab within seven weeks of starting therapy. A durable response was shown with 23 of 28 patients (82.1 percent) still responding at the time of analysis. Treatment-related adverse events were low grade (Grade 1 or 2) and seen in 62 patients (70.5 percent). The most common was fatigue (23.9 percent). Grade 3 adverse events were seen in four patients (4.5 percent) and included two cases of a reduction in lymphocytes in the blood and three cases of laboratory abnormalities relating to increased liver enzymes, blood cholesterol and blood creatine kinase. There were no Grade Four adverse events or death related to treatment.

"The typical patient with metastatic Merkel cell is a male in his mid-70s and often with co-morbid disease. A lot of patients in this population are unable to tolerate chemotherapy. Those who are may not see a response for up to three months, and side effects are likely. Our study shows the response to avelumab is not only durable for some patients but also rapid, which translates into a manageable quality of life for them," says Kaufman. "Yes, it may be a minor inconvenience to undergo an infusion for the treatment, but we're seeing patients leaving the clinic feeling well and heading out to normal activities like shopping or dinner -- not something we often see after chemotherapy is administered. The safety profile is remarkable. Side effects are easily managed and consistent with anti-PD-L1 antibodies in other tumor types," notes Kaufman. The team did report Grade 1 or 2 infusion reactions to avelumab in 17 percent of patients, but Kaufman notes that this was controlled, and in many cases could be prevented with pre-infusion medications.

Carrie Best of Ohio is believed to be the first patient globally to take avelumab as part of a clinical trial for Merkel cell carcinoma. A school psychologist with a young son, Best was diagnosed in her late 40s with an advanced form of disease in 2014 and was told by her community oncologist that her odds of recovery were "less than one percent." She researched her disease and met the criteria for the avelumab study led locally by Kaufman at Rutgers Cancer Institute of New Jersey. "After enduring various treatments including chemotherapy and a clinical trial leaving me physically and mentally exhausted, I wasn't sure what to expect with an investigational therapy," notes Best. "While on avelumab, I was able to get around easier, ride my bike and go to the park with my little boy. I started feeling relatively 'normal.' Six weeks after my first treatment, Dr. Kaufman told me my scans were clear and there was no evidence of disease. It was probably the most defining and powerful moment in my life, especially as I realized the improved quality of life I was afforded while receiving treatment. It was amazing to me that while I was in my most desperate hour, I was able to continue with the things most important to me -- being a wife and an active participant in my child's life, working in a job I love and being productive. I am truly grateful that other patients with advanced stage disease may have an opportunity to experience similar outcomes."

"A decade ago we might have one patient in my clinic with this type of advanced disease responding to treatment. Today, we have an opportunity for many more patients to respond with 'T-cell checkpoint inhibitor' drugs," notes Kaufman. "This study shows meaningful results and adds to emerging data showing promise with immunotherapy drugs in other forms of cancer."