The Targeted Pulse: Oncology Advancements and FDA Decisions

Welcome to this week's edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw FDA decisions, learned about care-changing trial data, heard from expert clinicians in the field, and analyzed long-term results. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

Giredestrant Outperforms Standard of Care in ER+/HER2– Early Breast Cancer

Interim data from the phase 3 lidERA trial demonstrate that giredestrant (GDC-9545), an oral selective estrogen receptor degrader, significantly outperforms standard endocrine therapy in patients with estrogen receptor-positive, HER2-negative early-stage breast cancer.

The trial met its primary end point by showing a statistically significant and clinically meaningful improvement in invasive disease-free survival. This marks giredestrant as the first agent in its class to show superior benefit in the adjuvant setting for this common breast cancer subtype. The safety profile was consistent with previous data, with no new safety signals observed. These results suggest giredestrant has the potential to become a new preferred endocrine therapy, paving the way for a major shift in the breast cancer treatment paradigm.

Zanidatamab Produces Survival Benefits in HER2+ Gastroesophageal Cancer

Topline results from the phase 3 HERIZON-GEA-01 trial show that the HER2-targeted bispecific antibody zanidatamab-hrii(Ziihera) plus chemotherapy offers significant survival benefits for patients with HER2-positive gastroesophageal adenocarcinoma (GEA).

Compared to the standard of care (trastuzumab plus chemotherapy), the zanidatamab combination achieved statistically significant and clinically meaningful improvements in progression-free survival. When combined with the PD-1 inhibitor tislelizumab (Tevimbra), the regimen also improved overall survival. The combination demonstrated enhanced response rates and duration of response with a manageable safety profile. These promising data suggest zanidatamab has the potential to become the new first-line standard of care for HER2+ GEA.

FDA Authorizes EXENT System to Aid Myeloma Diagnosis

The FDA has granted 510(k) clearance to the EXENT System, a fully automated device designed to aid in the diagnosis of multiple myeloma by assessing monoclonal gammopathies.

The system, developed by Thermo Fisher Scientific, integrates an immunoassay, mass spectrometry, and data review software. This integration provides clinical laboratories with an enhanced, efficient workflow to identify and measure monoclonal proteins in serum with improved sensitivity and specificity. The authorization confirms the system's substantial equivalence to other legally marketed devices, promoting more accurate and confident diagnoses for this heterogenous disease. The device is not yet formally evaluated for post-diagnosis long-term patient monitoring.

Breakthroughs in Cell Therapy: A New Era for HPV-Related Cancer Treatment

Breakthrough findings from 2 phase 2 clinical trials presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting highlight the revolutionary potential of cell therapies for human papillomavirus (HPV)-associated epithelial cancers.

One study reported that 2 patients with metastatic cervical cancer remain in complete remission a decade after receiving a single infusion of autologous tumor-infiltrating lymphocyte therapy. A second trial using genetically engineered T-cell receptor T cells showed robust antitumor activity and deep responses in patients with various metastatic HPV-associated cancers. Christian S. Hinrichs, MD, codirector of the Cancer Immunology and Metabolism Center of Excellence at Rutgers Cancer Institute and lead investigator of the 2 studies, spoke with Targeted Oncology^® about the significance of the findings and implications for integrating these novel cell therapies into clinical practice.

FDA Approves Selumetinib for Adult NF1 With Plexiform Neurofibromas

The FDA has approved selumetinib (Koselugo) for adult patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. This marks a significant expansion of the drug's label, which was previously only approved for pediatric patients.

The decision is supported by the phase 3 KOMET trial, where selumetinib showed a significantly higher confirmed objective response rate (20%) compared to placebo (5%) in adults. This approval addresses a critical unmet need for adults with NF1 and offers a new targeted therapeutic option for a condition often associated with pain and compromised quality of life.