Edgardo S. Santos Castillero, MD, FACP, FASCO
Articles by Edgardo S. Santos Castillero, MD, FACP, FASCO
This final segment broadens the discussion beyond TROP2 to explore the broader implications of QCS and computational pathology for biomarker development and clinical practice. Dr. Wistuba explains that QCS represents a platform capable of objectively quantifying protein expression across multiple cellular compartments, including membrane, cytoplasmic, nuclear, and immune cell populations, using digital image analysis. This flexibility creates opportunities to apply the approach to a wide range of biomarkers, including additional ADC targets, immune markers, and even routine diagnostic proteins.
Phase 3 trials test AI-scored Trop-2 NMR to guide first-line NSCLC ADC therapy, reshaping biomarker-driven treatment and lab adoption.
How Trop-2 NMR scoring may predict response to Trop-2 ADCs in NSCLC, why lower ratios matter, and what validation comes next.
Real-world studies show high concordance for AI TRK2‑NMR scoring in lung cancer; next, phase III trials test clinical validation.
Trop-2 levels alone fail to predict ADC response in lung cancer; an AI pathology biomarker (Trop-2 NMR) links cytoplasmic ratio to outcomes.
Trop-2 ADC trials in lung cancer show H-score fails to predict benefit, spotlighting drug internalization and target engagement as key efficacy drivers.
This segment examines the operational aspects of biomarker testing in non-small cell lung cancer, emphasizing the importance of multidisciplinary collaboration and efficient institutional workflows to ensure timely molecular testing, while highlighting the limitations of conventional TROP2 immunohistochemistry in predicting response to antibody-drug conjugate therapies and the need for more precise approaches such as computational pathology.
This segment introduces the program by emphasizing the critical role of comprehensive biomarker testing, including tissue-based next-generation sequencing, liquid biopsy, and immunohistochemistry, in guiding personalized treatment decisions for patients with non-small cell lung cancer.
Panelists discuss how emerging therapies like patritumab (a HER3-directed antibody-drug conjugate [ADC]), datopotamab (a TROP2 ADC), and ivonescimab (a PD-1/VEGF bispecific) show distinct toxicity profiles compared with existing treatments, potentially influencing earlier use. Balancing efficacy gains against toxicity risks remains critical in optimizing EGFR-mutated non–small cell lung cancer (NSCLC) treatment.
Panelists discuss how various strategies have been developed to enhance the tolerability of intravenous amivantamab, including premedication, step-up dosing, and infusion rate adjustments. Adoption into clinical practice varies, with many institutions integrating these approaches to mitigate infusion-related reactions and improve patient outcomes.
Panelists discuss how, if the MARIPOSA trial shows an overall survival advantage exceeding 1 year, the amivantamab-lazertinib combination may see increased frontline use. Subsequent therapy options could include chemotherapy, targeted therapies based on resistance mechanisms, or clinical trials for emerging treatments.
Panelists discuss how medical professionals consider continuing osimertinib with second-line and subsequent therapies based on disease progression, resistance mechanisms, and patient response. It may be combined with other agents or switched depending on clinical trials, biomarkers, and overall treatment goals to optimize outcomes.
Panelists discuss how medical professionals balance maximizing progression-free survival with preserving future treatment options by considering disease biology, resistance mechanisms, and patient factors. At first progression, the NCCN recommends continuing current therapy or switching to amivantamab with a platinum doublet, based on mutation status, prior response, toxicity, and patient preferences.
Panelists discuss how medical professionals use shared decision-making by aligning treatment options with patient values, discussing benefits, risks, and preferences. Patients often prioritize longest progression-free survival (PFS), lowest toxicity, and shortest infusion time. Collaborative discussions ensure personalized, evidence-based care.
Panelists discuss how disease-related factors like central nervous system (CNS) involvement or specific metastatic sites can guide treatment selection, favoring agents with CNS penetration or targeted efficacy. Mutational factors, such as TP53 comutations, may impact therapy response. Patient-related aspects, including age and comorbidities, influence tolerability and regimen choice.
Panelists discuss how, when discussing frontline regimens for EGFR-mutated non–small cell lung cancer (NSCLC), the NCCN-recommended options include osimertinib monotherapy for its targeted approach with lower toxicity; amivantamab/lazertinib combination for potentially deeper responses in specific mutations; and osimertinib with platinum-doublet chemotherapy for more aggressive disease requiring enhanced tumor control.
Key Takeaways in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD The panel concludes the discussion with key takeaways on the evolving treatment landscape in HER2 non–small cell lung cancer.
Treatment Considerations in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Experts on HER2 NSCLC provide clinical insights on selecting between antibody-drug conjugates and TKIs, treatment sequencing, and the role of chemoimmunotherapy.
Challenges and Unmet Needs in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD The expert panel shares its thoughts on current challenges and unmet needs in the overall HER2-mutated non–small cell lung cancer treatment landscape.
Adverse Events Associated With TKIs in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD D. Ross Camidge, MD, PhD, discusses the main adverse events seen with TKIs in patients with HER2-mutated non–small cell lung cancer.
First-in-Human Study of BAY2927088 in Advanced HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Martin Dietrich, MD, PhD, provides an overview of the first-in-human study of BAY2927088, a novel TKI, in patients with advanced HER2-mutated non–small cell lung cancer.
Beamion LUNG-1: Zongertinib in Advanced HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD The panel offers comprehensive insights on the Beamion LUNG-1 clinical trial, which is investigating zongertinib in patients with advanced HER2-mutated non–small cell lung cancer.
The Potential Role of TKIs in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Edward Kim, MD, MBA, describes the potential role of tyrosine kinase inhibitors (TKIs) in the treatment of patients with HER2-mutated non–small cell lung cancer.
Managing Adverse Events Associated With ADCs in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Lyudmila A. Bazhenova, MD, an expert on non–small cell lung cancer, provides clinical insights on the management of adverse events associated with antibody-drug conjugates.
DESTINY-Lung04: First-Line Trastuzumab Deruxtecan in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Edward S. Kim, MD, MBA, discusses the DESTINY-Lung04 trial, a study evaluating trastuzumab deruxtecan as first-line treatment for patients with HER2-mutated NSCLC.
The Role of Trastuzumab Deruxtecan in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Experts on HER2-mutated NSCLC discuss the patient populations in which they’d utilize trastuzumab deruxtecan and share their clinical experiences with the therapy.
DESTINY-Lung01 & DESTINY-Lung02: T-DXd in Metastatic HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Lyudmila A. Bazhenova, MD, and D. Ross Camidge, MD, PhD, review the DESTINY-Lung01 and DESTINY-Lung02 trials, and the panel provides its impressions of the data.
Role of ADCs in HER2-Mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD The panel discusses the role of antibody-drug conjugates (ADCs) and the treatment of patients with HER2-mutated non–small cell lung cancer.
Biomarker Testing Challenges in HER2-mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD Experts on HER2-mutated non–small cell lung cancer provide clinical insights on biomarker testing challenges and the role of reflex testing.
Diagnosing HER2-mutated NSCLC
ByEdgardo S. Santos Castillero, MD, FACP, FASCO,Martin Dietrich, MD, PhD,Edward S. Kim, MD, MBA,Lyudmila A. Bazhenova, MD,Ross Camidge, MD, PhD A panel of thoracic oncologists introduce themselves and discuss biomarker testing strategies and the diagnosis of HER2-mutated non–small cell lung cancer (NSCLC).
