Jacob Sands, MD

Panelists discuss how the concerning underutilization of first-line chemoimmunotherapy in extensive-stage SCLC may stem from clinical nihilism, lack of urgency in treatment initiation, and inadequate education about the substantial benefits these therapies provide to patients.

Panelists discuss how pneumonitis risk management requires intensive patient education about symptoms, close monitoring for several months post radiation, and multidisciplinary coordination with pulmonology and radiation oncology teams to distinguish between radiation-induced and immunotherapy-related pneumonitis.

Jacob Sands, MD, provides a post hoc analysis of TROPION-Lung01 , which showed improved intracranial activity and progression-free survival with datopotamab deruxtecan (Dato-DXd) versus docetaxel. Among patients with measurable brain metastases, Dato-DXd achieved a central nervous system confirmed overall response rate of 38%, with all evaluable patients showing disease control. No intracranial responses were seen in the docetaxel arm.

Panelists discuss how patient selection for durvalumab consolidation requires careful consideration of autoimmune diseases, baseline lung function, and neurologic paraneoplastic syndromes, while emphasizing that most patients should receive immunotherapy unless they have severely active contraindications.

Panelists discuss how durvalumab consolidation after chemoradiation has become the standard of care for limited-stage SCLC based on the ADRIATIC trial, with most patients being considered candidates for the 2-year treatment course.

Panelists discuss the introduction of quantitative cell scoring (QCS) for TROP2 as a significant artificial intelligence (AI)-driven advancement in oncology, emphasizing its ability to provide precise, quantitative biomarker assessment that complements molecular data like EGFR status. The panelists also highlight the importance of pathologists embracing digital pathology tools to enhance diagnostic accuracy and treatment planning while recognizing the technology’s early but promising role in expanding patient identification for targeted therapies and its potential broader impact on precision oncology.

Panelists discuss the expanding potential of quantitative cell scoring (QCS) technology beyond TROP2, highlighting its ability to assess not only cell surface expression but also internalization critical for antibody-drug conjugate (ADC) efficacy. They also emphasize how artificial intelligence (AI)-driven pathology advancements promise to streamline lung cancer diagnostics, improve predictive accuracy, and reduce variability in biomarker testing, ultimately enabling more precise patient selection and better integration of complex biomarker data into clinical care.

Panelists discuss the strategic approach to implementing targeted therapies through advanced biomarker testing, emphasizing the importance of prioritizing next-generation sequencing (NGS) early in diagnostic workflows due to limited tissue availability, the growing role of liquid biopsies, and emerging technologies like multiplex immunohistochemistry (IHC) to maximize tissue use. The panelists also highlight the critical need for close collaboration and clear communication between oncologists and pathologists to streamline testing, reduce redundant procedures, and ensure timely, personalized treatment decisions.

Panelists discuss how biomarker testing in oncology is evolving beyond genomic sequencing to include complex protein and RNA analyses, highlighting challenges such as limited biopsy tissue, the need for recent samples, and the importance of clear, standardized reporting; they emphasize that effective collaboration between oncologists and pathologists, along with the use of specialized send-out labs, will be critical to streamline workflows and ensure timely, actionable results for personalized patient care.

Panelists discuss the significant changes needed to integrate quantitative continuous scoring (QCS) and TROP2 normalized membrane ratio (NMR) assays into routine clinical practice, emphasizing the current limited adoption of digital pathology, the likely use of artificial intelligence (AI)-based assays as send-out tests initially, and the importance of expanding digital infrastructure and collaboration to enable precise, automated biomarker evaluation that can guide personalized oncology treatment.

Panelists discuss several ongoing clinical trials, including AVANZAR and TROPION-Lung10, that are investigating the predictive utility of TROP2 normalized membrane ratio (NMR) in guiding treatment with datopotamab deruxtecan combinations in lung cancer while highlighting advances in artificial intelligence (AI)-driven pathology to refine biomarker assessments and emphasizing the need for prospective validation to establish NMR’s role in clinical practice.

Panelists discuss how data from the TROPION-PanTumor01, TROPION-PanTumor02, and TROPION-Lung02 studies reinforce the predictive value of the TROP2 normalized membrane ratio (NMR) biomarker across diverse patient populations and treatment regimens, highlighting its reproducibility and ability to specifically identify patients likely to benefit from datopotamab deruxtecan–based therapies rather than serving as a general prognostic marker.

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.