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Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort.

Authors :
Italiano A
Bessede A
Pulido M
Bompas E
Piperno-Neumann S
Chevreau C
Penel N
Bertucci F
Toulmonde M
Bellera C
Guegan JP
Rey C
Sautès-Fridman C
Bougoüin A
Cantarel C
Kind M
Spalato M
Dadone-Montaudie B
Le Loarer F
Blay JY
Fridman WH
Source :
Nature medicine [Nat Med] 2022 Jun; Vol. 28 (6), pp. 1199-1206. Date of Electronic Publication: 2022 May 26.
Publication Year :
2022

Abstract

Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781). The primary endpoint was the 6-month non-progression rate (NPR). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. The 6-month NPR and ORRs for cohorts in this trial enrolling all comers were previously reported; here, we report the results of a cohort enrolling patients selected based on the presence of TLSs (n = 30). The 6-month NPR was 40% (95% confidence interval (CI), 22.7-59.4), so the primary endpoint was met. The ORR was 30% (95% CI, 14.7-49.4). In comparison, the 6-month NPR and ORR were 4.9% (95% CI, 0.6-16.5) and 2.4% (95% CI, 0.1-12.9), respectively, in the all-comer cohorts. The most frequent toxicities were grade 1 or 2 fatigue, nausea, dysthyroidism, diarrhea and anemia. Exploratory analyses revealed that the abundance of intratumoral plasma cells (PCs) was significantly associated with improved outcome. These results suggest that TLS presence in advanced STS is a potential predictive biomarker to improve patients' selection for pembrolizumab treatment.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Details

Language :
English
ISSN :
1546-170X
Volume :
28
Issue :
6
Database :
MEDLINE
Journal :
Nature medicine
Publication Type :
Academic Journal
Accession number :
35618839
Full Text :
https://doi.org/10.1038/s41591-022-01821-3