Which sarcoma requires PD1/PDL1 inhibitors, and what should be the best scheme? Present status and next steps.

Abstract

Purpose of review: The introduction of immune checkpoint inhibitors (ICI) in advanced sarcoma has been largely disappointing due to their "cold" tumor microenvironment, characterized by low tumor mutational burden, scarce CD8 + T-cell infiltration, and minimal expression of PD-1/PD-L1. However, recent findings highlight several scenarios in which immune checkpoint blockade exhibits clinical efficacy.

Recent findings: ICIs have shown durable efficacy in specific sarcoma subtypes, such as alveolar soft part sarcoma (ASPS), with objective response rates (ORR) exceeding 35% and 50%, in monotherapy or in combination, respectively. Doxorubicin-based regimens plus ICIs have yielded notorious and higher ORRs in the most common sarcoma subtypes, than historical chemotherapy data. Neoadjuvant radiation therapy combined with ICIs has significantly improved disease-free survival in localized selected soft tissue sarcomas.

Summary: Immunotherapy targeting immune checkpoints in sarcomas is evolving, with recent findings highlighting its potential. Single-arm trials underscore the efficacy of ICIs in rare sarcomas, exemplified by the FDA approval of atezolizumab for ASPS. Combination strategies are proving more effective than chemotherapy alone, with ongoing comparative studies assessing chemo-immunotherapy in both metastatic and localized sarcomas. Advances in predictive biomarkers could expand the clinical use of ICIs.