Antibodies blocking the PD-1 pathways have demonstrated a durable response in treating various cancers, many pharmaceutical companies have since joined the race to develop and experiment the use of PD-1/PD-L1 immune checkpoint inhibitors. Recently, the Cancer Immunotherapy Trials Network (CITN)’s CITN-09/KEYNOTE-017 phase 2 trial has published the latest data on using pembrolizumab in patients with advanced Merkel Cell Carcinoma (aMCC), naïve to systemic therapy,1 which has led to the approval of a new indication.2 The study results were published in the Journal of Clinical Oncology.1
Pembrolizumab is the first PD-1 inhibitor approved by the U.S. Food and Drug Administration (FDA) back in 2014.3 Including the recent approval for treating MCC, pembrolizumab has already received approvals to treat 11 different types of cancers.3
MCC is a rare but aggressive skin cancer that is often fatal.4 PD-1 inhibitors have been previously tested in aMCC and demonstrated increased progression-free survival (PFS) compared with historical chemotherapy data, but the impact on overall survival (OS) and duration of response were still unknown.1
This phase 2 multicenter trial recruited 50 adults with aMCC who had never been treated with systemic therapy.1 They were given 2mg/kg pembrolizumab every 3 weeks for up to 2 years.1 In a median follow-up time of 14.9 months (range, 0.4-36.4 months), 28 patients (56%) achieving an objective response, with 12 of them (24% in the treatment population) achieved complete response.1 Among the 28 responders, median response duration was not reached (range 5.9-34.5+ months).1 PFS and OS at 24 months was 48.3% and 68.7%, respectively.1 Median PFS was 16.8 months, and median OS was not reached when the study ended.1
Grade ≥3 treatment-related adverse events (AEs) were observed in 14 (28%) patients.1 Seven (14%) patients had to withdraw from the treatment due to the treatment-related AEs, of which one case was treatment-related death.1 The most common immune-mediated AEs observed during the study were hypothyroidism and pneumonitis, both occurring in 6% of the study population.5
The corresponding author of the study, Dr. Paul Nghiem of the Department of Dermatology/Medicine, University of Washington, Seattle, concluded during an interview with the ASCO® Post, “Here, we present the longest observation to date of patients with [advanced Merkel cell carcinoma] receiving first-line anti–programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile and favorable [overall survival] compared with historical data from patients treated with first-line chemotherapy.”
Of note, the new indication of pembrolizumab was granted based on the tumor response rate and durability of response under the accelerated approval track.2,3 Continued approval from the FDA for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.2,3
1. Nghiem P, Bhatia S, Lipson EJ, et al. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019:JCO. 18.01896.
2. FDA approves pembrolizumab for Merkel cell carcinoma. 2018. U.S. Food and Drug Administration. (Accessed March 15, 2019, at https://www.fda.gov/Drugs/InformationOnDrugs/
3. KEYTRUDA U.S. Prescribing Information., Merck & Co., Inc. Approved February 2019.
4. Wang TS, Byrne PJ, Jacobs LK, et al. Merkel cell carcinoma: update and review. Presented at: Seminars in cutaneous medicine and surgery;
5. Stenger M. 2019. First-Line Pembrolizumab in Advanced Merkel Cell Carcinoma. The ASCO Post. (Accessed March 15, 2019, at http://www.ascopost.com/News/59755.)