Anne Chiang, MD, PhD, Yale Cancer Center

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.

Anne Chiang, MD, PhD, discusses treating patients with advanced non–small cell lung cancer without driver mutations.

Expert oncologists provide an overview of the landscape surrounding small-cell lung cancer and highlight the importance of early referral and diagnosis for overall patient outcomes.

Anne Chiang, MD, PhD, discusses recent advancements in the biological understanding and treatment of small cell lung cancer.

Panelists conclude their discussion by commenting on areas of unmet need and sharing personal perspectives on factors that may change clinical practice for SCLC in the future.

Key opinion leaders in lung cancer share personal thoughts on the potential for bispecific agents and the overall impact of inhibiting molecular targets.

Anne Chiang, MD, PhD, reviews the study design of 2 clinical trials, adding a third agent to the standard-of-care regimen of chemotherapy plus I/O; Stephen Liu, MD, discusses clinical trials in limited-stage disease.

Thoracic oncology expert Vivek Subbiah, MD, provides an overview of recent clinical trials studying agents targeting DNA damage for the treatment of small cell lung cancer.

Expert panelists weigh in on emerging data from recent presentations on small cell lung cancer, including novel immunotherapy approaches such as bispecific antibodies targeting DLL3 or therapies targeting TIGIT.

Anne Chiang, MD, PhD, renowned expert in thoracic oncology, guides a discussion on whether to rechallenge with chemotherapy + I/O after progression of small cell lung cancer.

Key opinion leaders in thoracic oncology provide insights into second-line treatment for patients with relapsed/refractory small cell lung cancer and comment on the role of trilaciclib in managing cisplatin-associated neutropenia.

Lung cancer expert Anne Chiang, MD, PhD, considers the recent withdrawal of FDA-accelerated approval for nivolumab and pembrolizumab for patients with relapsed extensive-stage small cell lung cancer.

Vivek Subbiah, MD, reviews the safety and efficacy of treatment with lurbinectedin in patients who have platinum-sensitive relapsed small cell lung cancer.

Panelists reflect on treatment considerations for asymptomatic brain metastases, progress in biomarker research, and frequency of administering checkpoint inhibitors.

Panelists reflect on key points from recent studies in ES SCLC by discussing patients for whom immunotherapy may be appropriate, examining the role of adding CTLA4 inhibition to a PD-L1 inhibitor, and reviewing factors to consider when deciding between cisplatin or carboplatin.

Key opinion leader in lung cancer, Vivek Subbiah, MD, examines the phase 3 KEYNOTE-604 trial of platinum-based chemotherapy + pembrolizumab and considers whether the data support findings from other trials of chemotherapy + IO combination approaches.