In a French phase II study reported in The Lancet Oncology, Delyon et al found that pembrolizumab produced a high response rate in patients with classic or endemic Kaposi sarcoma with progressive cutaneous extension requiring systemic treatment.

As stated by the investigators, “Although the treatment of iatrogenic and human immunodeficiency virus–related Kaposi sarcoma is well defined and mostly based on restoring immune function, the treatment of classic and endemic Kaposi sarcoma is less well established. Chemotherapy or [interferon-alfa] is used for patients with extensive cutaneous or visceral Kaposi sarcoma, but tolerance might be poor and long-term remission is rare.”

Study Details

In the proof-of-concept trial, 17 patients with classic (n = 8) or endemic (n = 9) disease enrolled from three French hospitals between July 2018 and December 2019 received pembrolizumab at 200 mg every 3 weeks for 6 months. The primary endpoint was the best overall response rate within the 6-month time frame, defined by investigator-assessed complete or partial response using the modified AIDS Clinical Trial Group criteria. The primary endpoint was to be considered met if a 30% response rate was achieved.  

Responses

Median follow-up was 20.4 months (interquartile range [IQR] = 18.1–24.1 months). A complete response was observed in 2 patients (12%) and partial response was observed in 10 (59%), yielding a best overall response rate of 71% (95% confidence interval [CI] = 44%–90%). The remaining five patients (29%) achieved stable disease. A response was observed in six of nine patients with endemic Kaposi sarcoma (including complete response in two) and in six of eight with classic Kaposi sarcoma.

Median time to response was 4.8 months (IQR = 3.4–12.0 months), and estimated median duration of response was 23.4 months (95% CI = 21.2 months–not evaluable). Among all patients, the median time to disease progression was 24 months (95% CI = 15 months–not evaluable).

Adverse Events

Treatment-related adverse events of any grade occurred in 13 patients (76%), with the most common being diarrhea and pruritus in 3 patients (18%) each. Treatment-related grade 3 adverse events occurred in two patients, consisting of acute reversible cardiac decompensation in one and granulomatous reaction in mediastinal lymph nodes in one; no grade 4 events were observed.

Adverse events led to discontinuation of treatment in two patients, due to grade 3 cardiac decompensation and grade 2 pancreatitis. No serious adverse events or treatment-related deaths were observed.

The investigators concluded, “In this prospective trial, which to our knowledge is the first to assess the role of PD-1 blockade in patients with classic and endemic Kaposi sarcoma, pembrolizumab showed promising antitumor activity with an acceptable safety profile. If this result is supported by further studies, treatment with anti–PD-1 could be part of the therapeutic armamentarium for patients with classic and endemic Kaposi sarcoma.”

Julie Delyon, PhD, of the Department of Dermatology, AP-HP Saint-Louis Hospital, Paris, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by MSD France. For full disclosures of the study authors, visit thelancet.com.