In a French phase II basket trial (AcSé Pembrolizumab) reported in The Lancet Oncology, Jean-Yves Blay, MD, and colleagues investigated the activity and safety of pembrolizumab in patients with rare sarcomas. AcSé Pembrolizumab is an ongoing phase II multitumor study investigating the activity of pembrolizumab monotherapy in rare cancers.
Jean-Yves Blay, MD
Study Details
In the multicenter study, 97 patients with rare types of advanced sarcomas that were untreated or resistant to treatment were enrolled between September 2017 and December 2020 and treated with pembrolizumab at 200 mg every 21 days for a maximum of 24 months. The primary endpoint was investigator-assessed objective response rate at week 12; best response to treatment during any point in the study was a secondary endpoint.
Key Findings
By histotype, 34 patients had chordomas, 14 had alveolar soft-part sarcomas; 12 had SMARCA4-deficient sarcomas or malignant rhabdoid tumors; 8 had desmoplastic small round cell tumors; 6 had epithelioid sarcomas; 4 had dendritic cell sarcomas; 3 each had clear cell sarcomas, solitary fibrous tumors, and myxoid liposarcomas; and 10 had other ultrarare histotypes.
At week 12, objective responses (all partial) were observed in 6 (6.2%, 95% confidence interval [CI] = 2.3%–13.0%) of 97 patients. An additional 42 patients (43%) had stable disease.
At data cutoff in April 2022, median follow-up was 13.1 months (range = 0.1–52.8 months; interquartile range = 4.3–19.7 months). Best responses by histotype included objective response in 4 (12%) of 34 chondromas; 8 (57%) of 14 alveolar soft-part sarcomas; 3 (25%) of 12 SMARCA4-deficient sarcomas or malignant rhabdoid tumors; 1 (13%) of 8 desmoplastic small round cell tumors; and 1 (17%) of 6 epithelioid sarcomas. Median response duration was 11.3 months (95% CI = 8.3 months to not reached).
The most common grade 3 or 4 adverse events were anemia (8%), increased alanine aminotransferase (6%) and aspartate aminotransferase (6%), and dyspnea (5%). Serious adverse events occurred in 37 patients (38%), most commonly gastrointestinal disorders (12%) and respiratory, thoracic, and mediastinal disorders (11%). No treatment-related deaths were reported.
The investigators stated, “Our data show the activity and manageable toxicity of pembrolizumab in some rare and ultrarare sarcoma histotypes, and support the PD-1/PD-L1 pathway as a potential therapeutic target in selected histotypes. The completion of the basket study will provide further evidence regarding the activity and toxicity of pembrolizumab in identified rare types of cancer.”
Dr. Blay, of Centre Léon Bérard & Université Claude Bernard Lyon 1, Lyon, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by The Ligue contre le cancer, INCa, and MSD. For full disclosures of the study authors, visit thelancet.com.
