Pembrolizumab can produce responses in some patients with rare sarcomas, according to research published in The Lancet Oncology.
Responses were observed in patients with chordoma, alveolar soft part sarcoma, SMARCA4-deficient sarcoma or malignant rhabdoid tumors, desmoplastic small round cell tumors, and epithelioid sarcoma.
These results come from a phase 2 trial (ClinicalTrials Identifier: NCT03012620) that enrolled patients with unresectable, locally advanced or metastatic rare cancers. The current analysis included 97 patients with sarcoma. They had a median age of 51 years at baseline, and 55% were men. Most patients had received prior therapy, but 19 had not.
Eighteen subtypes of sarcoma were represented. The most common subtypes were chordoma (n=34), alveolar soft part sarcoma (n=14), SMARCA4-deficient sarcoma or malignant rhabdoid tumors (n=12), desmoplastic small round cell tumors (n=8%), epithelioid sarcoma (n=6), dendritic cell sarcoma (n=4), clear cell sarcoma (n=3), solitary fibrous tumors (n=3), and myxoid liposarcoma (n=3). Other ultra-rare subtypes comprised 10% of the cohort.
The patients received pembrolizumab at 200 mg on day 1 of each 21-day cycle for a maximum of 24 months or until disease progression. Patients ultimately received a median of 6 cycles (range, 1-35). Nearly all patients (n=95) had discontinued treatment at the data cutoff.
At week 12, the objective response rate (ORR) was 6%, with no complete responses (CRs) and 6 partial responses (PRs).
When the researchers assessed best response, the ORR was 17%, with 2 patients achieving a CR and 15 achieving a PR. By cancer type, the best ORR was:
- 57% among patients with alveolar soft part sarcoma (1 CR and 7 PRs)
- 25% among patients with SMARCA4-deficient sarcoma or malignant rhabdoid tumors (3 PRs)
- 17% among patients with epithelioid sarcoma (1 CR)
- 13% among patients with desmoplastic small round cell tumors (1 PR)
- 12% among patients with chordoma (4 PRs).
With a median follow-up of 13.1 months, the median overall survival (OS) was 19.7 months. The median OS was not reached among patients with chordoma or alveolar soft part sarcoma. It was 7.4 months in patients with desmoplastic small round cell tumors, 2.8 months in those with SMARCA4-deficient sarcoma/malignant rhabdoid tumors, 2.5 months in epithelioid sarcoma patients, and 7 months for all other subtypes combined.
The median progression-free survival (PFS) was 2.8 months overall, 6.6 months in patients with alveolar soft part sarcoma, 6.1 months in chordoma patients, 2.3 months in epithelioid sarcoma patients, 2.0 months in patients with SMARCA4-deficient sarcoma or malignant rhabdoid tumors, 2.0 months in patients with desmoplastic small round cell tumors, and 2.1 months for the other subtypes combined.
The most common grade 3-4 adverse events (AEs) were anemia (8%), alanine aminotransferase and aspartate aminotransferase increase (6%), and dyspnea (5%). There were 86 serious AEs in 37 patients. Five patients had fatal AEs, but none were considered related to treatment.
“Our data support the PD-1/PD-L1 pathway as a potential therapeutic target, especially in chordoma, SMARCA4-deficient sarcoma or malignant rhabdoid tumor, and as previously reported, in alveolar soft part sarcoma, in locally advanced or metastatic disease, untreated or progressing after standard treatments,” the researchers wrote. “Nonetheless, the clinical activity of pembrolizumab needs to be further confirmed in expanded cohorts and prospective studies with a careful monitoring of real-world data.”
Disclosures: This research was partly supported by Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Blay J-Y, Chevret S, Le Cesne A, et al. Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSé Pembrolizumab): Analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial. Lancet Oncol. Published online July 7, 2023. doi:10.1016/S1470-2045(23)00282-6