Targeted Therapies and Genomic Testing Take Center Stage at ASCO 2025

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, a wave of practice-changing data were presented across solid tumors and hematologic malignancies, reinforcing the growing role of personalized medicine and novel immunotherapies in shaping pharmacy practice.

Chicago, IL | Image Credit: © Spiroview Inc. - stock.adobe.com

In breast cancer, the SERENA-6 trial (NCT04964934) demonstrated that circulating tumor DNA–guided switching from an aromatase inhibitor to camizestrant (AZD9833; AstraZeneca)—a next-generation oral selective estrogen receptor degrader (SERD)—plus a cyclin-dependent kinase 4/6 inhibitor significantly improved progression-free survival (PFS) in patients with ESR1-mutated HR+/HER2– advanced disease (16.0 vs 9.2 months; HR, 0.44). Complementing this, precision oncology discussions highlighted how ESR1 and PIK3CA mutations influence endocrine resistance, with SERDs such as elacestrant and camizestrant offering new avenues. Datopotamab deruxtecan (Dato-DXd; Datroway; AstraZeneca, Daiichi Sankyo), a TROP2-directed antibody-drug conjugate, also showed promise in endocrine-pretreated HR+/HER2– breast cancer.

In lung cancer, tarlatamab (Imdelltra; Amgen, Inc), a DLL3-targeted bispecific
T-cell engager, improved overall survival in relapsed small cell lung cancer (SCLC) compared with chemotherapy (13.6 vs 8.3 months; HR, 0.60) in the phase 3 DeLLphi-304 trial (NCT05740566). The agent, granted FDA accelerated approval in 2024, also demonstrated improved patient-reported outcomes. For HER2-mutated non–SCLC, zongertinib (BI 1810631; Boehringer Ingelheim) improved physical functioning and symptom burden while maintaining a favorable safety profile in the Beamion LUNG-1 trial (NCT04886804).

In hematologic malignancies, epcoritamab (Epkinly; Genmab US and AbbVie), a
CD20xCD3 bispecific T-cell engager, sustained long-term remission in relapsed/refractory large B-cell lymphoma. Three-year data from EPCORE NHL-1 (NCT03625037) showed 96% of complete responders remained in remission, with median PFS reaching 37 months. Similarly, measurable residual disease (MRD)-guided strategies in multiple myeloma are gaining traction. Trials such as ATLAS (NCT02659293) and MRD2STOP (NCT04108624) suggest patients with sustained MRD negativity may safely de-esca- late or discontinue therapy, informing a shift toward treatment individualization.

The microbiome also emerged as a key determinant of immunotherapy efficacy. Experts warned that antibiotics may impair immune responses, reduce survival, and increase treatment resistance due to gut dysbiosis. Fecal microbiota transplantation and dietary interventions are being explored to restore microbial balance and boost immunotherapy effectiveness.

In the realm of precision medicine, pretreatment DPYD genotyping was shown to reduce fluoropyrimidine-related toxicities and hospitalizations, while saving costs—a finding that aligns with updated National Comprehensive Cancer Network guidelines recommending universal testing prior to fluoropyrimidine chemotherapy.

Together, these studies reflect a shifting oncology landscape where pharmacists play a central role in optimizing biomarker-driven care, implementing genomic testing, managing novel immunotherapies, and addressing supportive care challenges.