This week’s Targeted Pulse summarizes key oncology developments reported at the 2025 American Society of Hematology Annual Meeting and Exposition and the San Antonio Breast Cancer Symposium (SABCS).
Targeted Oncology reader polls highlighted several SABCS abstracts. In HR+/HER2– early breast cancer, the phase 3 lidERA study showed the oral SERD giredestrant met its primary endpoint with a statistically significant and clinically meaningful improvement in invasive disease‑free survival (IDFS) versus standard endocrine therapy. The phase 3 ASCENT‑07 trial in HR+/HER2– metastatic breast cancer did not meet its primary endpoint of progression‑free survival (PFS) for sacituzumab govitecan versus chemotherapy. For HER2‑positive disease, HER2CLIMB‑05 (tucatinib combination) met its PFS primary endpoint. Safety and quality‑of‑life data from ASCENT‑04 (sacituzumab govitecan plus pembrolizumab in triple‑negative breast cancer) are scheduled for presentation.
The phase 3 MajesTEC‑3 trial showed the bispecific BCMA‑directed T‑cell engager teclistamab plus subcutaneous daratumumab (Tec‑Dara) significantly improved outcomes in patients with relapsed/refractory multiple myeloma who had 1–3 prior lines of therapy. Tec‑Dara reduced the risk of disease progression or death by 83% (median PFS not reached vs 18.1 months) and reduced the risk of death by 54% (36‑month overall survival rate 83.3% vs 65.0%). The combination yielded higher complete response rates (81.8% vs 31.1%) and greater MRD negativity, with a manageable safety profile, supporting its consideration as a new standard‑of‑care option in earlier lines.
ASCENT‑07, which evaluated sacituzumab govitecan as first‑line chemotherapy after endocrine therapy in HR+/HER2– metastatic breast cancer, failed to show a PFS benefit by blinded independent central review; median PFS was 8.3 months in both arms. An early OS trend favored sacituzumab but data remain immature (27% maturity). The sacituzumab arm had higher rates of grade ≥3 treatment‑emergent adverse events (72% vs 48%). Sacituzumab govitecan retains its established role in the post‑chemotherapy setting based on TROPiCS‑02.
Patient‑reported outcomes from the phase 3 DESTINY‑Breast09 trial indicate trastuzumab deruxtecan (T‑DXd; Enhertu) plus pertuzumab is a tolerable first‑line alternative for HER2+ advanced/metastatic breast cancer. Compared with taxane plus trastuzumab and pertuzumab, T‑DXd plus pertuzumab maintained similar physical function and comparable control of pain and fatigue. The T‑DXd arm reported more gastrointestinal side effects but fewer skin/mucosal symptoms and less extremity swelling, with overall similar tolerability over time.
A long‑term, exploratory analysis of the phase 3 ALTTO trial favors aromatase inhibitors as adjuvant endocrine therapy for HR+/HER2+ early breast cancer. With a median follow‑up of 9.9 years, aromatase inhibitor use was associated with a higher 10‑year disease‑free survival rate (80.1% vs 76.5% for SERMs; adjusted HR 0.65) and longer time to distant recurrence, without compromising overall survival. The benefit was observed across menopausal subgroups; in premenopausal patients, aromatase inhibitors with or without ovarian function suppression outperformed SERM‑based regimens for 10‑year DFS.
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