Clinical studies indicate that an inhibitor of the immune checkpoint reduces tumors in almost half of patients with incurable, extended form of the common skin cancer, according to a New England Journal magazine.
"These results suggest a possible paradigm shift in the treatment of patients with advanced squamous cell carcinoma of the skin, which currently has very limited results with the help of chemotherapy and targeted therapy", - said lead author Michael Migden, MD, associate professor of dermatology.
Migden is the principal investigator registration international multicenter phase II clinical trial cemiplimab, immune checkpoint inhibitor that works by blocking PD1, surface receptor on T cells, which disables the immune response to cancer.
Cutaneous squamous cell carcinoma is the second most common cancer of the skin, with an annual estimated 1 million new cases. More than 95 percent of patients are cured by surgery and radiation in the early stages of the disease. The researchers said that the faction is progressing, there is no systemic therapy approved as a standard of care.
By observing the average 7.9 months in 28 of 59 patients with metastatic disease (47.5%) had an objective response to cemiplimab, 30% decreased tumor. Four fully responded, 24 - partially, and 82% of the respondents were on the drug.
"Patients continue to do well, so the average progression-free survival and overall survival has not yet been reached", - said Migden, Mohs surgeon and dermatological oncology. Prolonged disease control level of respondents and patients with stable disease for at least 105 days was 61 percent. Migden noted that the response rate to chemotherapy regimens or therapies targeted against epidermal growth factor receptor (EGFR), currently used for the treatment of squamous cell carcinoma of skin cancer, varies from 15-25 percent, while there are many debilitating side effects.
Immunotherapy is a risk of inflammatory side effects that need to be controlled, but otherwise they have a smaller number of daily events than chemotherapy and EGFR inhibitors, Migden said.
Common side effects in the phase II study cemiplimab were diarrhea, fatigue, nausea, constipation and rash. Four patients (6.8%) had to discontinue treatment. Three patients died of adverse events during the trial, but the deaths were not considered related to treatment.
The mean age of patients in phase II study was 71 years old, of whom 33 (55.9%) received provisional systemic therapy and 50 (84.7%) received radiotherapy.
In phase I study in patients with metastatic or locally advanced, unresectable disease but 13 out of 26 (50%) had a partial response. During the 11 months follow-up, seven patients remained in the response. Two patients (7.7%) had to discontinue treatment due to adverse events. The median age was 73 years.
The US administration by the Food and Drug Administration has granted an application for a breakthrough therapy for drug status, providing a faster way for a potential approval of FDA.
Cutaneous squamous cell carcinoma develops due to genetic damage caused by UV radiation. These tumors have a high mutation load, providing a target environment for the immune system and the cancer is also strongly associated with immunosuppression. These factors have made it a strong candidate for the inhibition of PD1, which unleashes the immune system to fight cancer.
Cutaneous squamous cell carcinoma is not included in the national cancer registries, so the incidence of the disease and its mortality is unknown. Assessment or annual diagnoses range from 700,000 to 1 million. According to one study, in 2012, died from 3900 to 8700 people from this cancer.