Jacob Sands, MD

Panelists discuss the TROPION-LUNG01 trial results, highlighting how datopotamab deruxtecan improved progression-free survival (PFS) in nonsquamous non–small cell lung cancer (NSCLC) and the role of the TROP2 normalized membrane ratio (NMR) as a predictive biomarker that helps identify patients most likely to benefit from the therapy.

Panelists discuss preclinical findings supporting TROP2 normalized membrane ratio (NMR) as a predictive biomarker for datopotamab deruxtecan, highlighting its ability to quantify functional membrane expression and internalization potential, refine patient selection beyond conventional immunohistochemistry (IHC), and drive broader adoption of artificial intelligence (AI)-powered digital pathology in precision oncology across multiple tumor types.

Panelists discuss the limitations of conventional immunohistochemistry (IHC) in assessing TROP2 expression for targeted therapies in non–small cell lung cancer and highlight how advanced tools such as quantitative continuous scoring (QCS) and normalized membrane ratio (NMR) offer more precise, objective, and functional evaluations of protein expression and internalization, paving the way for improved patient stratification and personalized treatment with antibody-drug conjugates (ADCs).

Panelists discuss the limitations of conventional immunohistochemistry (IHC) in assessing TROP2 expression for targeted therapies in non–small cell lung cancer and highlight how advanced tools such as quantitative continuous scoring (QCS) and normalized membrane ratio (NMR) offer more precise, objective, and functional evaluations of protein expression and internalization, paving the way for improved patient stratification and personalized treatment with antibody-drug conjugates (ADCs).

Panelists discuss the evolving role of advanced biomarker tools like quantitative continuous scoring (QCS) and normalized membrane ratio (NMR) in non–small cell lung cancer (NSCLC), highlighting their potential to overcome limitations of traditional TROP2 assessment, improve prediction of antibody-drug conjugate (ADC) efficacy, and enhance patient selection through more precise and functional tumor profiling.

Jacob Sands, MD, discusses ways to manage the toxicities associated with the DLL3 inhibitor tarlatamab in the treatment of patients with SCLC.

Panelists discussed the evolving small cell lung cancer treatment landscape, emphasizing the need to improve clinical trial accessibility, advance biomarker research, and better manage brain metastases, while highlighting promising therapies like checkpoint inhibitors and antibody-drug conjugates that offer hope for durable responses amid ongoing challenges.

Panelists discussed the challenges of biomarkers in SCLC, emphasizing that targets like DLL3 and B7-H3 show promise but require dynamic monitoring, and highlighted ongoing trials exploring antibody-drug conjugates and targeted therapies to potentially complement or replace platinum chemotherapy in personalized treatment approaches.

Panelists discussed advances in overcoming resistance in extensive-stage small cell lung cancer, highlighting promising antibody-drug conjugates and immune-based therapies targeting DLL3 and B7-H3, including bispecific T-cell engagers and CAR T cells, while emphasizing the critical need for biomarkers to guide therapy selection and optimize combinations to improve durability, intracranial activity, and patient outcomes amid the challenges of relapse and immune evasion.

Panelists highlighted a forthcoming large cooperative-group trial in small cell lung cancer that pioneers precision medicine by using molecular subtyping to guide biomarker-driven therapy combined with immunotherapy, aiming to personalize treatment across diverse patient populations and generate extensive molecular and clinical data to advance understanding and improve outcomes in this historically challenging disease.

Panelists emphasized that clear, compassionate, and ongoing communication with patients diagnosed with small cell lung cancer is vital to support informed decision-making amid evolving treatment options, highlighting the importance of maintaining a broad therapeutic arsenal, integrating multidisciplinary and palliative care early, and regularly reassessing goals to optimize quality of life and treatment outcomes throughout the often prolonged disease course.

Panelists discussed real-world data confirming that a novel targeted agent for extensive-stage small cell lung cancer offers consistent efficacy and durable responses across multiple lines of therapy, with a favorable toxicity profile enhancing quality of life; treatment selection is individualized based on patient factors and logistical considerations, while vigilant brain metastasis surveillance and multidisciplinary coordination remain essential to optimize outcomes.

Panelists highlighted a pivotal phase 3 trial demonstrating that a novel targeted therapy significantly improves overall survival and offers durable responses in second-line small cell lung cancer, positioning it as a preferred option after frontline chemoimmunotherapy despite logistical challenges and the need for multidisciplinary coordination, with careful patient selection and ongoing clinical trials essential to optimizing sequencing and expanding treatment options.

Panelists emphasized that while the addition of the new drug to maintenance therapy marks a major advance with improved survival, it also brings increased toxicity that necessitates careful patient selection and shared decision-making—especially considering real-world tolerability, impacts on quality of life, subsequent treatment sequencing, and the unresolved questions around its use in patients with brain metastases, underscoring the need for biomarkers and individualized care in this evolving treatment landscape.

Panelists highlighted the M40 trial’s promising results showing that adding chemotherapy to atezolizumab maintenance after initial chemo-immunotherapy significantly improves overall survival in extensive-stage disease, offering a new strategy to reduce relapse risk during the vulnerable post-induction period with manageable toxicity, and marking a potential shift in the treatment paradigm for extending long-term patient outcomes.

Panelists discussed the nuanced management of brain metastases in small cell lung cancer, highlighting the preference for systemic therapy first in asymptomatic cases to avoid upfront radiation adverse effects, the selective use of stereotactic radiosurgery for symptomatic lesions, and the cautious, individualized approach to thoracic consolidation radiation amid concerns about toxicity and mixed data, emphasizing the critical role of multidisciplinary collaboration and ongoing research to optimize treatment strategies.

Panelists reviewed first-line treatment for extensive-stage SCLC, emphasizing platinum-based chemotherapy plus a PD-L1 inhibitor—typically carboplatin with either atezolizumab or durvalumab—with 4 cycles standard, noting both agents offer survival benefits and are largely interchangeable, while highlighting emerging therapies and ongoing trials that may soon refine and personalize this evolving treatment landscape.

Panelists highlighted the ADRIATIC trial’s survival benefits with durvalumab in LS-SCLC while discussing exploratory data that identified immune microenvironment features distinguishing long-term responders from early progressors, emphasizing the need for validated biomarkers to personalize immunotherapy and improve outcomes beyond current standards.

Panelists discussed the importance of close monitoring during consolidation durvalumab in LS-SCLC—especially for pneumonitis risk—and noted that relapse management is shifting away from routine platinum rechallenge toward more personalized use of newer agents like lurbinectedin and tarlatamab, based on timing, tolerability, and individual patient factors.

Panelists emphasized that while timely initiation of durvalumab post chemoradiation is ideal in LS-SCLC, consistent with ADRIATIC trial protocols, patient recovery and multidisciplinary input—especially in cases involving treatment-related toxicity or neurologic comorbidities—are essential to guide safe, individualized decision-making.

Panelists agreed the ADRIATIC trial is practice-changing for limited-stage small cell lung cancer, establishing durvalumab as the new standard post chemoradiation due to its significant survival benefit and manageable toxicity, while also highlighting the need for multidisciplinary coordination and raising questions about agent selection and evolving radiation strategies.

Jacob Sands, MD, presents promising early-phase trial results for obrixtamig, a novel DLL3-targeting T-cell engager, in patients with large cell neuroendocrine carcinoma of the lung (LCNEC-L), shared at ESMO Congress 2024.

Panelists discuss the unmet needs and future perspectives in the treatment of RET-positive non–small cell lung cancer (NSCLC), focusing on areas for improvement in therapy and the potential for new treatment strategies.

Panelists discuss how to monitor patients for response to treatment and early signs of resistance in RET fusion–positive non–small cell lung cancer (NSCLC), including the approach to follow-up molecular testing, and describe strategies for treatment sequencing after disease progression on RET inhibitors.

Panelists discuss the common adverse effects for patients receiving selpercatinib or pralsetinib, strategies for managing these effects, and whether differences in the safety profiles of these drugs influence treatment choices for RET fusion–positive non–small cell lung cancer.

Panelists discuss the situations in which other first-line therapies, such as cabozantinib or PD-L1–positive chemotherapy options, might be considered for RET fusion–positive non–small cell lung cancer (NSCLC), and compare the role of chemotherapy and immunotherapy to that of RET inhibitors in this setting.

Panelists discuss the specific factors that influence the decision to initiate one of the NCCN guideline–preferred RET inhibitors, selpercatinib or pralsetinib, over the other in the treatment of RET fusion–positive NSCLC.

Panelists discuss their initial impressions of a patient case with RET fusion–positive non–small cell lung cancer (NSCLC), treatment goals for newly diagnosed patients, and the key patient and disease characteristics considered when selecting a first-line treatment regimen.

Panelists discuss the initial approach to the management of RET-positive non–small cell lung cancer (NSCLC), focusing on treatment strategies and the role of targeted therapies such as RET inhibitors in first-line treatment.

Panelists discuss how to balance the need for comprehensive biomarker testing with the urgency to initiate treatment in patients with advanced disease and explore situations where treatment might be started before test results are available.