EZ peasy.

Sarcoma and lymphoma are two of the most heterogeneous malignancies out there, making them the perfect candidates for basket trials evaluating therapies based on genetic signature versus simply histology. This iteration looks at the novel therapy tazemetostat targeting the enzyme EZH2, which is constitutively active in cancers with a deleterious mutation in the tumor suppressor SMARCB1 encoding INH1 or an activating mutation in EZH2. Such is the case in 90% of epithelioid sarcomas and 20% of follicular lymphomas, the impetus for this phase 2 basket trial. The primary endpoint of objective response rate was 9/62 among epithelioid sarcoma with a documented loss of INH1 expression or biallelic mutation in SMARCB1, 31/45 (69%) among refractory follicular lymphoma with a EZH2 mutation and in 19/54 (35%) without a EZH2 mutation. In either case, grade 3+ adverses events were in the single-digits. TBL: The EZH2-targeted therapy tazemetostat is an intriguing new way to tackle relevant cancers. | Gounder & Morschhauser, Lancet Oncol 2020