First Drug Approved for Merkel Cell Carcinoma Achieves Strong Response

Merkel cell carcinoma; AACR: Merkel cell carcinoma; AACRWASHINGTON, D.C.—Up until recently, patients with advanced Merkel cell carcinoma (MCC) had little hope of a durable treatment for their rare, aggressive skin condition, which is considered more deadly than melanoma. Although stage IV MCC, which affects about 2,000 newly diagnosed U.S. patients each year, can be treated with chemotherapy, the responses are seldom durable, said Howard L. Kaufman, MD, Surgical Oncologist at Rutgers Cancer Institute of New Jersey and Professor of Surgery and Medicine at the Rutgers Robert Wood Johnson Medical School. So the approval of avelumab for advanced MCC by the FDA March 23, 2017, was good news for patients and oncologists, said Kaufman at the annual meeting of the American Association for Cancer Research (AACR), held April 1-5. This is the first-ever drug approved by the FDA for MCC; it was approved for treatment of metastatic MCC in adults and pediatric patients 12 years and older. The agency's accelerated approval is contingent upon confirmatory trials. Patients With Merkel Cell “This is a terrible disease,” said Kaufman at a news briefing at the AACR meeting. “Avelumab monotherapy showed durable antitumor activity and manageable safety in patients with metatastic Merkel cell carcinoma that progressed after chemotherapy.” Avelumab targets the PD-L1 protein; the impetus for studying patients with MCC came from studies showing that PD-L1 is found in tumor samples from almost all patients who have MCC. It is “often associated with Merkel cell polyomavirus infection” and “exposure to UV light, advanced age, and immunosuppression elevate risk,” noted Kaufman. Because it is so rare, “this is a disease that oncologists don't see so much,” said Kaufman. Therefore, it is important to get the word out so patients can have access to avelumab. “MCC is an orphan disease,” commented briefing moderator Suzanne Topalian, MD, Director of the Melanoma Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore. “This is a disease primarily of older patients,” with an average age of about 73. Although the immune systems of older people are frequently less competent, Topalian noted that the response of older patients to avelumab was good and it was relatively well-tolerated. In fact, Kaufman said older patients responded just as well as younger patients to avelumab and, interestingly, they seemed to have somewhat fewer side effects than younger patients. “I think that age in and of itself should not be a contraindication for use of the drug,” he noted. The most common side effects were fatigue and infusion reactions. Results With Avelumab Kaufman and his colleagues enrolled 88 patients with metastatic MCC who had progressed after treatment with chemotherapy in a multi-center, phase II clinical trial. All patients on the trial received 10 mg/kg avelumab as an IV infusion over 1 hour every 2 weeks. As shown in previously reported data, 28 patients had a response after 10.4 months of follow-up. Eight had a complete response and 20 had partial responses. The trial demonstrated that avelumab works in patients with highly mutated cancers typically caused by UV light and also in those with minimally mutated tumors triggered by the Merkel cell polyomavirus. At the AACR meeting, Kaufman reported on a longer follow-up; the number of MCC patients with a response increased to 29, for an overall response rate of 33 percent after a median of 16.4 months, which Kaufman called “quite remarkable.” The number of patients with a complete response increased to 10, while another patient newly recorded to have a response had a complete response. When the data cutoff time occurred, 21 of the responses were ongoing and the median duration of response had not been reached. Kaufman and his team estimate that 74 percent of patients with metastatic MCC will have a response to avelumab that lasts 1 year or longer. He added that “maturing progression-free and overall survival data suggest long-term benefit in a proportion of patients.” During his presentation, Kaufman said avelumab is also being evaluated for other cancers. Asked by Oncology Times what those are, he named bladder, lung, gastric, ovarian, and renal cancers. “It does look like there is activity against other cancers,” said Kaufman. But while avelumab is being studied in a variety of other cancers, he emphasized it has not been approved for such indications in the U.S., Canada, or elsewhere. In a statement made available at the AACR meeting, an Oregon MCC patient treated with avelumab described what the drug has meant to him. Tom Judd received his first infusion of avelumab more than 2 years ago under the care of one of Kaufman's study co-authors, Paul Nghiem, MD, PhD, Director of the Skin Oncology Program at the Seattle Cancer Care Alliance and Head of Dermatology at the University of Washington. Judd's MCC, which initially appeared as a pimple-like bump on his face in 2012, had spread through his vital organs, and he and his family were preparing for a dismal prognosis. But 6 weeks after Judd received his initial infusion of avelumab, a scan showed that 35 percent of his tumor had disappeared, and today it is 90 percent gone. “I feel very lucky, if that's a word that can be used, that I'm living in this time and in this area that this can even happen,” said Judd, who feels well and enjoys working in his garden and babysitting his preschool-aged granddaughter. Judd still receives infusions of the drug every 2 weeks at the Seattle Cancer Care Alliance. Nghiem called the latest response rates in the trial “extraordinarily durable,” and said such treatment responses are “unheard of.” Peggy Eastman is a contributing writer.

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