Three established cancer therapies — Enhertu (trastuzumab deruxtecan, Daiichi Sankyo Europe), Piqray (alpelisib, Novartis Europharm), and Trodelvy (sacituzumab govitecan, Gilead Sciences) — moved closer to expanded use in the EU after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended extensions of indication for all three at its July 2026 meeting. 

The changes would move these agents earlier in treatment, introduce new combinations, or broaden access within biomarker-selected populations.

Enhertu 

The CHMP granted a positive opinion recommending Enhertu in combination with pertuzumab for the first-line treatment of adults with unresectable or metastatic HER2-positive breast cancer. If approved by the European Commission, the regimen would become a new first-line treatment option for HER2-positive metastatic breast cancer in the EU after more than a decade without change in the standard first-line approach.

Enhertu is a HER2-directed antibody-drug conjugate that pairs trastuzumab with a topoisomerase I inhibitor payload. The drug works by binding HER2-expressing tumor cells and releasing its cytotoxic payload intracellularly, with a bystander effect that also affects neighboring tumor cells with lower HER2 expression. 

Supporting data for the expanded use of Enhertu include results from the phase 3 DESTINY-Breast09 trial, which compared trastuzumab deruxtecan plus pertuzumab against the long-standing standard of taxane, trastuzumab, and pertuzumab (THP) in treatment-naive metastatic disease. 

The combination reduced the risk for disease progression or death by 44% vs THP and extended median progression-free survival to approximately 40.7 months, compared with 26.9 months for THP. Investigators described this as the first meaningful improvement in the first-line setting in more than a decade. HER2-positive disease affects roughly 15%-20% of patients with metastatic breast cancer, and despite a decade of THP as the standard first-line regimen, most patients still experience disease progression within 2 years and about 1 in 3 never receive a second line of treatment.

Piqray 

For Piqray, the revised indication broadens use to patients whose disease progressed after an endocrine-based regimen given as monotherapy and adds biomarker-based patient-selection guidance.

The drug is now indicated, in combination with fulvestrant, in postmenopausal women and men with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer with a PIK3CA mutation after progression on such treatment.

Piqray works by inhibiting PI3K alpha, blocking a signaling pathway frequently activated by PIK3CA mutations that drive resistance to endocrine therapy. The CHMP did not mention any clinical trial results supporting this decision. 

The drug’s original approval was based on the phase 3 SOLAR-1 trial, in which median progression-free survival was nearly doubled with alpelisib plus fulvestrant vs fulvestrant alone (11.0 vs 5.7 months) in patients with a PIK3CA mutation. About 40% of patients with HR-positive, HER2-negative metastatic breast cancer carry a PIK3CA mutation, which independently predicts shorter progression-free and overall survival. If approved, the revised indication could extend use of Piqray to a broader group of patients with endocrine-resistant disease, including some previously treated with CDK4/6 inhibitor combinations.

Trodelvy 

The CHMP also recommended Trodelvy, in combination with pembrolizumab, as first-line therapy in previously untreated adults with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 with a combined positive score of 10 or higher.

Trodelvy is a Trop-2-directed antibody-drug conjugate. It targets Trop-2, a surface antigen expressed on more than 90% of breast tumors, and delivers SN-38, a topoisomerase I inhibitor, via a hydrolyzable linker, producing direct cytotoxicity in Trop-2-expressing cells along with a bystander effect on neighboring tumor cells.

Supporting data for the new Trodelvy combination include results from the phase 3 ASCENT-04/KEYNOTE-D19 trial, in which previously untreated, PD-L1-positive patients were randomly assigned to receive to sacituzumab govitecan plus pembrolizumab vs chemotherapy plus pembrolizumab. The combination significantly prolonged progression-free survival (11.2 vs 7.8 months; hazard ratio, 0.65), reducing the risk for progression or death by 35%. The 12-month progression-free survival rate was 48% vs 33% for chemotherapy, and no new safety signals were identified for either agent. Roughly 40% of metastatic TNBC tumors are PD-L1-positive and tend to behave more aggressively with shorter survival. If approved, this combination could expand first-line options for this biomarker-selected group.