Updated survival data of more than 5 years follow-up were presented at the 2021 ASCO Annual Meeting, demonstrating the long-term survival benefits of treatment with the immune checkpoint inhibitor Bavencio (avelumab), a PD-L1 inhibitor, in patients with metastatic (spreading) Merkel-cell carcinoma, an aggressive type of skin cancer.
These new results confirm the current use of avelumab as the standard of care for patients whose cancer progressed after 1 or more lines of chemotherapy.
Avelumab, a monoclonal antibody, was the first immunotherapy to be approved by the FDA for the treatment of patients with metastatic Merkel-cell carcinoma, based on earlier results from the JAVELIN Merkel 200 clinical trial.
Improved Survival with Avelumab
The new, long-term survival data from the JAVELIN Merkel 200 study presented at the ASCO meeting showed an average survival of 12.6 months with avelumab, a significant survival benefit compared with second or third chemotherapy in patients with metastatic Merkel-cell carcinoma, according to Paul T. Nghiem, MD, PhD, Head of the Division of Dermatology at the University of Washington Medical Center in Seattle, Washington, who presented the study results.
“Results of the longest follow-up study to date of patients with metastatic Merkel-cell carcinoma treated with an immune checkpoint inhibitor demonstrated meaningful long-term overall survival,” Dr. Nghiem said.
“After more than 5 years of follow-up, these results further support the role of avelumab as a standard of care for patients with metastatic Merkel-cell carcinoma who have disease progression following 1 or more lines of chemotherapy,” he added.
Advanced Merkel-Cell Carcinoma
Metastatic Merkel-cell carcinoma is an aggressive type of skin cancer, according to Dr. Nghiem. In the past, before the introduction of immunotherapy, this type of skin cancer was associated with only a 14% 5-year survival from the time of diagnosis, meaning that only about 14% of patients with metastatic Merkel-cell carcinoma survived for 5 years.
Furthermore, Dr. Nghiem said, in the past, patients whose cancer stopped responding to chemotherapy did not survive more than 1 year.
The JAVELIN Merkel 200 Study Results
All patients in this study had metastatic (stage IV) Merkel-cell carcinoma that progressed after 1 or more previous lines of chemotherapy. A total of 88 patients were included in the study, and all received treatment with avelumab. At the study cutoff date of September 25, 2020, the average follow-up of patients was more than 5 years (65.1 months).
The results showed that the average survival with avelumab among all the patients in the study was just more than 1 year (12.6 months).
However, this long-term study showed that 30% of the patients with metastatic Merkel-cell carcinoma who received avelumab survived for 4 years, and 26% of the patients survived for 5 years or more—almost double the historical rate of survival before the introduction of immune checkpoint inhibitors.
Of note, all patients who received the PD-L1 inhibitor (avelumab) had a response to therapy, regardless of whether their cancer expressed the PD-L1 protein or not. However, the overall survival was longer in patients whose cancer expressed the PD-L1 protein versus those whose cancer did not have the PD-L1 protein.
Specifically, the average survival was 12.9 months in patients with PD-L1 expression compared with only 7.3 months in the patients without PD-L1, and the 5-year survival was 28% in the patients with PD-L1 compared with 19% in those without PD-L1.
“The overall survival benefit in both subgroups greatly exceeds that seen in retrospective analysis of second-line or later chemotherapy,” Dr. Nghiem emphasized.
By 5 and a half years, 19 (21.9%) patients in the study discontinued using avelumab but continued to be followed-up, and 63 (71.6%) patients had died. Of these, 49 (55.7%) patients died of cancer progression, the most common cause of death.
In total, 26 patients received subsequent treatments for skin cancer, including 4 patients who continued to use avelumab; 4 patients who switched to the PD-1 inhibitor Keytruda (pembrolizumab), which has more recently also received FDA approval for use in patients with Merkel-cell carcinoma; and 4 patients received combination chemotherapy with carboplatin and etoposide.
- Merkel-cell carcinoma is an aggressive type of skin cancer; before the introduction of immunotherapy, only 14% of patients survived 5 years from the time of diagnosis
- Avelumab, a monoclonal antibody, was the first immunotherapy to be approved by the FDA for the treatment of patients with metastatic Merkel-cell carcinoma
- A long-term study showed that 30% of the patients with metastatic Merkel-cell carcinoma who received avelumab survived for 4 years, and 26% of the patients survived for 5 years or more
- This is almost double the historical rate of survival before the introduction of immune checkpoint inhibitors
- Furthermore, in patients with the PD-L1 protein expression on their cancer cells, the 5-year survival was 28%, compared with 19% in those without PD-L1