Julia Rotow, MD

Panelists discuss ongoing research and investigational strategies aimed at overcoming resistance in ROS1-driven lung cancer.

Panelists discuss translating clinical trial evidence on ROS1-targeted therapy into real-world patient management.

Panelists discuss the role of ALK rearrangements in lung cancer and the development of successive generations of targeted inhibitors.

Panelists discuss long-term data demonstrating the durability of response and intracranial protection achieved with modern ALK-targeted therapies.

Panelists discuss the molecular and clinical characteristics of ROS1-driven lung cancer and the role of precise molecular testing in guiding targeted therapy.

Panelists discuss first-line treatment strategies for ROS1-positive lung cancer and the factors influencing therapy selection and sequencing.

An expert discusses updated overall survival results from the phase 2 PHAROS study evaluating encorafenib plus binimetinib in patients with BRAF V600E–mutant metastatic non–small cell lung cancer (mNSCLC).

Julia Rotow, MD, and Jyoti Malhotra, MD, MPH, discuss unmet needs in advanced NSCLC.

Julia Rotow, MD, and Jyoti Malhotra, MD, MPH, discuss novel biomarkers under investigation in advanced NSCLC.

Julia Rotow, MD, and Jyoti Malhotra, MD, MPH, discuss the investigation of sigvotatug vedotin plus pembrolizumab in NSCLC.

Julia Rotow, MD, and Jyoti Malhotra, MD, MPH, discuss the investigation of sigvotatug vedotin in nonsquamous NSCLC.

Julia Rotow, MD, and Jyoti Malhotra, MD, MPH, discuss unmet needs in second-line non–small cell lung cancer.

Julia Rotow, MD, and Jyoti Malhotra, MD, MPH, discuss the rationale for evaluating IB6 as a target in non–small cell lung cancer.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.