Julia Rotow, MD

Articles

Looking Ahead in NSCLC Oncodrivers and Targeted Therapies

July 23rd 2025

Panelists discuss how ASCO 2025 highlighted exciting advances in targeted therapy including neoadjuvant approaches, dynamic biomarkers like circulating tumor DNA, mixed results with HER3-directed antibody-drug conjugates (ADCs) in the EGFR space, but promising data with trastuzumab-based ADCs, emphasizing the critical importance of comprehensive biomarker testing to ensure no patients miss potentially life-changing targeted therapies.

Real-World (RW) Outcomes and Novel Strategies in ROS1-Positive NSCLC

July 16th 2025

Panelists discuss how real-world data becomes crucial for guiding treatment decisions in rare subsets like ROS1-positive patients where head-to-head trials are challenging, and how next-generation inhibitors like NVL-520 and taletrectinib aim to improve efficacy while reducing TRK-related toxicities through more selective targeting.

Assessing Frontline TKIs and Treatment Considerations in ROS1-Positive Advanced NSCLC

July 16th 2025

Panelists discuss how the ROS1 inhibitor landscape has evolved from crizotinib to entrectinib and now repotrectinib as the current standard of care, with repotrectinib showing impressive 35.7-month median PFS in treatment-naive patients despite increased dizziness toxicity, while next-generation agents like NVL-520 aim to spare TRK toxicity.

Emerging Strategies for Overcoming On/Off-Target Resistance in ALK-Positive NSCLC

July 9th 2025

Panelists discuss how resistance mechanisms in ALK-positive disease are driving development of next-generation inhibitors like NVL-655 that spare TRK to reduce neurocognitive toxicity while targeting compound resistance mutations, though the success of lorlatinib makes frontline trials challenging due to extremely long progression-free survival requiring decade-long studies.

Decoding Efficacy and Safety Outcomes Among Second- and Third-Generation ALK Inhibitors

July 9th 2025

Panelists discuss how lorlatinib has become the new standard of care for ALK-positive patients based on CROWN trial data showing unprecedented 5-year progression-free survival (60% at 5 years, median not reached) and superior central nervous system control compared with earlier agents like alectinib, despite unique metabolic and neurocognitive toxicities requiring careful management.

New Frontiers in KRAS Inhibition for Patients With NSCLC

July 2nd 2025

Panelists discuss how next-generation KRAS G12C inhibitors like divarasib, lifirafenib, and RMC-6291 (a RAS-ON inhibitor) show promising enhanced potency with response rates in the 50% range and extended PFS, offering hope for more effective treatment options and potential sequencing strategies.

CNS Surveillance and Management of Brain Metastases in Patients With KRAS G12C NSCLC

July 2nd 2025

CNS Metastases Management in KRAS G12C Patients Central nervous system (CNS) metastases affect approximately 40% of patients with KRAS G12C positive non–small cell lung cancer, presenting significant management challenges. Unlike EGFR- and ALK-positive patients who benefit from highly CNS-penetrant targeted agents, KRAS G12C patients have limited systemic options with proven intracranial activity. Stereotactic radiosurgery often becomes the preferred approach for CNS lesions, particularly when systemic options are exhausted after platinum-based chemotherapy and immunotherapy. For asymptomatic, small CNS metastases (≤5 mm without edema), systemic therapy initiation with close monitoring represents a reasonable approach. Immunotherapy and chemoimmunotherapy combinations demonstrate modest CNS response rates, while KRAS G12C inhibitors show approximately 40% to 43% intracranial response rates in untreated brain metastases. However, these response rates remain below 50%, necessitating careful patient monitoring and readiness for local ablative therapy. Surveillance strategies for CNS metastases vary among practitioners, with baseline MRI universally recommended but routine follow-up imaging practices differing. Some oncologists perform periodic surveillance scans for high-risk patients, while others monitor symptomatically. The lack of robust CNS activity from systemic agents emphasizes the importance of early detection and prompt local therapy intervention when CNS progression occurs.

Targeting KRAS: Emerging Frontline Options for Patients With NSCLC

June 25th 2025

Panelists discuss how KRAS G12C inhibitors are moving into frontline combination therapy with immunotherapy, highlighting KRYSTAL-7 data showing impressive efficacy in PD-L1–high patients (~28 months progression-free survival) but more modest results in PD-L1–low patients, with ongoing studies exploring optimal combination strategies.

Managing KRAS Inhibitor Safety and Hepatotoxicity

June 25th 2025

Panelists discuss how KRAS G12C inhibitors differentiate in their toxicity profiles, with sotorasib carrying higher hepatotoxicity risk especially post–checkpoint inhibitor therapy, while adagrasib shows more gastrointestinal toxicities, and the importance of washout periods to mitigate liver toxicity.

Evaluating Efficacy Outcomes of TKI Therapies in KRAS G12C-Mutated NSCLC

June 18th 2025

Panelists discuss how 2 FDA-approved KRAS G12C inhibitors (adagrasib and sotorasib) perform in second-line therapy after immunotherapy and chemotherapy, with both showing improved progression-free survival versus docetaxel despite modest gains, leading to their adoption as standard of care due to better tolerability profiles.

KRAS G12C-Mutated NSCLC: Current Treatment Paradigms

June 18th 2025

Panelists discuss how critical broad-panel next-generation sequencing is for all patients with non–small cell lung cancer to enable biomarker-guided treatment, with focus on KRAS G12C mutations found in 12% to 14% of patients and consideration of PD-L1 expression levels and comutations when selecting frontline therapy.

Future Treatment Options in EGFR-Mutant NSCLC

April 7th 2025

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.

Amivantamab Toxicity Mitigation Strategies in the Treatment of EGFR-Mutant NSCLC

April 7th 2025

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.

Treatment Sequencing in the Second Line and Beyond in EGFR-Mutant NSCLC

March 31st 2025

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.

Expert Thoughts on Continuing Osimertinib Therapy Beyond First Disease Progression in EGFR-Mutant NSCLC

March 31st 2025

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.

Maximizing Time on Therapy to Preserve Future Treatment Options in EGFR-Mutated NSCLC

March 24th 2025

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.

Approaches to Patient Shared Decision-Making in EGFR-Mutated NSCLC

March 24th 2025

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.

EGFR-Mutated NSCLC Disease Risk Stratification

March 17th 2025

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.

Frontline Treatment Options in Metastatic EGFR-Mutated NSCLC

March 17th 2025

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.

Leveraging ctDNA Platforms in High-Risk Patients: Current Applications and Future Potential

December 6th 2024

Panelists discuss how they currently utilize emerging ctDNA platforms for high-risk patients and explore whether these advancements will soon become standard practice in clinical decision-making.

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