Dr Kaufman speaks with ecancertv at ASCO 2016 to discuss the results of phase II JAVELIN Merkel 200 trial, in which patients with metastatic Merkl cell carcinoma received avelumab, a PD-L1 checkpoint inhibitor.

Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with Merkel cell polyomavirus, with limited therapeutic options after 1st-line chemotherapy.

Dr Kaufman describes the results of the JAVELIN trial in which, of a cohort of 88, six patients (9.8%) achieved complete responses, 12 (19.7%) had partial responses, and 7 (11.5%) had stable disease (83.3% responses were ongoing).

He also details the ongoing progression free survival data, and offers that additional clinical evaluation of avelumab for is warranted.

Isaac Brownell, MD, PhD of the National Cancer Institute, Bethesda, MD discusses the virus associated with Merkel cell carcinoma and ongoing research into a potential vaccine for the disease during his attendance at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Unlike in other skin cancers, Dr Brownell explains that Merkel cell carcinoma is associated with a virus, which may explain why the immune system is able to target so many of the tumors. Viruses express proteins which are not usually expressed in the body, which gives a natural target for the immune system. Because these tumors are driven by a virus and it is necessary for the viral proteins to be expressed, the tumor needs to figure out a way to protect itself from the immune detection of that viral protein, which may be another reason that checkpoint inhibitors are effective in Merkel cell carcinoma. The virus associated with Merkel cell carcinoma is abundant in the environment and can be found on most people’s skin and does not appear to cause any issues. During cancer, the virus is integrated into the host DNA and the virus proteins become mutated which drives tumor formation. Dr Brownell believes developing a vaccine against this virus would not likely be effective as there is not a strong correlation between infection and tumor formation. However, research into vaccines against the tumor formation are ongoing, with the aim to develop a vaccine specifically for patients with Merkel cell carcinoma, which would augment the immune response.

Patients with metastatic Merkel cell carcinoma (MCC) that does not respond to chemotherapy have a very poor survival rate after 1-2 years, representing a great unmet need. Here, Paul Nghiem, MD, PhD, from the University of Washington, Seattle, WA, discusses the preliminary results of the Phase II JAVELIN Merkel 200 trial (NCT02155647) evaluating the efficacy and safety of avelumab for chemotherapy-refractory MCC. This interview was recorded at the American Society of Oncology (ASCO) 2018 Annual Meeting, held in Chicago, IL.

Isaac Brownell, MD, PhD of the National Cancer Institute, Bethesda, MD discusses current studies into Merkel cell carcinoma while attending the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. According to Dr Brownwell, with rare cancers like Merkel cell carcinoma, studies are typically small as it is difficult to recruit a large number of patients. Over time, as more patients are treated a better understanding can be achieved. In each trial, the drug was either given before or after conventional chemotherapy was tried, it is necessary to test the drug in both conditions to show whether the drugs work in treatment resistant cancer or cancer that has never been treated with another type of drug. These type of trials are ongoing as well as additional trials to learn more about the mechanism by which checkpoint inhibitors help control Merkel cell carcinoma and to answer the question – why does Merkel cell carcinoma seem to respond more than other solid tumors to checkpoint inhibitors?

The event will include MCC support groups, lab tours, poster session, and a presentation highlighting the progress in MCC research over the past year.

Isaac Brownell, MD, PhD of the National Cancer Institute, Bethesda, MD gives an overview of his talk on new treatment approaches for Merkel cell carinoma held at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Merkel cell carcinoma is a rare neuroendocrine cancer of the skin and it is more deadly than melanoma on a case by case basis. Patients with advanced disease had very few treatment options according to Dr Bownell; they would respond to conventional chemotherapy but progress rapidly. In order to find better treatment for these patients, two spearate research groups have tested different checkpoint inhbitiors; checkpoint inhibitors activate the immune sytem to attack the cancer. Both studies have had positive results and immune checkpoint inhibitors may soon be the standard of care for advanced Merkel cell carcinoma. The results show that a large group of patients with advanced Merkel cell carcinoma (metastatic disease that has left the skin) responsded to checkpoint inhbitor therapy, i.e. their tumors shrank. Further, patients who responded tended to keep their responses. According to Dr Brownell, the hope is that these drugs can cure Merkel cell carcinoma.

Martin Mihm, Jr., MD of Brigham and Women's Hospital, Boston, MA gives an overview of the session on open quesions in dermatopahtology of cutaneous tumors held at the World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Prof. Mihm held the first talk [overview available in a separate video]. First, he discusses the talk by Dr Klaus Busam about the diagnosis of desmoplastic melanoma; this tumor presents as a firm hard nodule like a scar. Dr Busam further discussed the use of molecular techniques to look for mutations that help to make a differntial diagnosis. The reason that a correct diagnosis is important is that desmoplastic melanoma is a lesion that recurs locally and can go along nerves, in the head and neck and even into the brain. The second talk Prof. Mihm discusses was by Dr Raymond Barnhill on spitzoid melanocytic neoplasms. The spitzoid lesions were originally described as melanoma in childhood as they were thought to occur in children and to be benign. It is now known that there is a spitz lesions that can be excised and does not recur. However, there are variants, which have been problematic. Dr Barnhill reviewed the field and the best course is to realize that these lesions are not black and white; some may be borderline lesions and should be excised, and rarely, lesions can metastesize. Finally, Prof. Mihm discusses the talk by Dr Arthur Sober on staging of Merkel cell carcinoma. Merkel cell carcinoma is a very rare tumor but it is very aggressive. In the new staging system, a large population of patients was analyzed. They found that lesions that present without any evidence of mitosis, have a good survival whereas if they have a node, survival falls; and if they have metastatic diseae, the survival is much worse. The talk gave a detailed understanding of how to better stage the lesions in order to look for better treatments for them according to Prof. Mihm.

Axel Hauschild, MD, PhD of the University Hospital Schleswig-Holstein, Kiel, Germany, discusses the exciting new data on Merkel cell carcinoma presented at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Prof. Hauschild speaks about interesting data recently published in the New England Journal of Medicine and Lancet Oncology on two drugs, a PDL-1 antibody called avelumab and a PD-1 antibody pembrolizumab, which have shown to be effective in the treatment of Merkel cell carcinoma. Prof. Hauschild believes that a new standard of care can be defined for Merkel cell carcinoma and chemotherapy will take a backseat in the near future. Immunotherapy with checkpoint blockade is replacing current chemotherapy because it has shown to have more and longer responses which means better overall survival (OS).