Checkpoint inhibitors may offer hope for patients with Merkel cell carcinoma, a rare and aggressive skin cancer without any viable treatment options.
A Phase 2 trial of Merck’s anti-PD-L1 avelumab reported that the treatment was effective in a large proportion of patients, while other clinical trials reported similar data for other checkpoint-blocking molecules.
Although platinum-based chemotherapy is used often in Merkel cell carcinoma, the hopeless state of the treatment situation is exemplified by the fact that published guidelines recommend clinical trials as a standard of care.
About 50% to 60% of patients do respond to chemotherapy, but the effects are usually short-lived, and such treatment does not improve survival, which is about nine months after chemotherapy.
The clinical trial (NCT02155647) recruited 88 patients with advanced Merkel cell carcinoma from North America, Europe, Australia and Asia, all of whom had previously been treated unsuccessfully with chemotherapy.
The study used an open-label design and all patients received avelumab. Patients received 10 mg per kg bodyweight of avelumab as intravenous injections every two weeks. An independent review committee assessed the response to treatment, using Response Evaluation Criteria in Solid Tumors (RECIST), a set of published rules that define improvement in cancer patients.
Patients in the study were followed for a median of 10.4 months. Among the 88 patients, 28 (or 31.8%) were judged to respond to the drug. Eight had a complete response, while the rest had a partial response. At the time of data analysis, 23 of the patients who responded still had an ongoing response, indicating the effect was durable.
The treatment was considered very safe. Four patients, making up 5% of the group, experienced five events of treatment-related adverse events classified as grade 3 (severe, but not life-threatening). Although 43 patients died during the trial, the deaths were not related to the treatment, and a majority died of the cancer. Researchers also noted immune-related side effects, but these were almost exclusively mild.
Based on the results of the study, the U.S. Food and Drug Administration granted avelumab breakthrough, fast-track, and orphan drug designation — nominations that will allow a more speedy development and review of the drug for Merkel cell carcinoma. (Orphan drugs are those that target rare diseases.)
Meanwhile, the European Medicines Agency is reviewing Merck’s Marketing Authorization Application for avelumab for Merkel cell carcinoma.
In a linked comment, also published in The Lancet Oncology, Axel Hauschild, MD, from the University Hospital Schleswig-Holstein, and Dirk Schadendorf, MD, University Hospital Essen (both dermatologists and Merck consultants) underscored that the findings really change the options for patients with Merkel cell carcinoma.
“For the first time, there is some optimism on the horizon for treating patients with Merkel cell carcinoma and hopefully this will also expand to other non-melanoma skin cancers,” they wrote, while also mentioning that other attempts with checkpoint inhibitors in this cancer type are underway.
Since there now is no doubt that Merkel cell carcinoma responds to cancer immunotherapy, the duo argued that clinical trials also should explore if combinations of various checkpoint blockers can further boost the effectivity of this type of treatment.
The clinical trial is still recruiting participants. See the trial page at NCT02155647 for contact information and locations.