Stephen Liu, MD, is an associate professor of medicine at Georgetown University, as well as the director of Thoracic Oncology and head of Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.

Emerging Strategies for ALK+ NSCLC

Panelists explore emerging therapeutic strategies focused on enhancing selectivity and minimizing off-target effects. Research includes novel inhibitors, degraders, and combination regimens that may improve outcomes in resistant disease.

They stress that early-phase clinical trials have shown promising signals of activity even in heavily pretreated patients. The development of these strategies underscores the ongoing innovation within precision oncology for lung cancer.

Panelists conclude that as new agents progress through clinical evaluation, the field is moving closer to long-term disease suppression and improved survival in patients with treatment-resistant ALK-positive disease.

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Panelists discuss novel research directions aimed at overcoming resistance and extending survival in ALK-positive lung cancer.

Resistance Mechanisms and Molecular Testing in ALK Inhibitor–Treated NSCLC

Panelists explain that resistance to targeted therapy often arises through secondary mutations or bypass signaling pathways. Recognizing these patterns is critical for sequencing subsequent therapies effectively. Advanced molecular testing, including plasma-based assays, allows clinicians to identify emerging resistance early and adjust treatment accordingly.

The conversation also explores new research mapping the molecular evolution of ALK-positive disease under treatment pressure. These insights are enabling the development of next-generation inhibitors designed to overcome resistance mutations.

Overall, panelists emphasize that incorporating molecular monitoring at progression helps ensure continued precision in therapy selection and sustains long-term disease control.

Panelists discuss mechanisms of acquired resistance to ALK inhibition and how molecular testing guides sequencing strategies.

Real-World Data in ALK+ NSCLC

Panelists highlight that real-world data provide valuable insights into treatment effectiveness across broader patient populations than those typically represented in clinical trials. They discuss how differences in comorbidities, adherence, and health care access affect outcomes and underscore the need to contextualize trial results accordingly.

Real-world studies confirm that the efficacy and tolerability observed in trials translate well to routine clinical settings. However, they also reveal challenges in maintaining adherence and managing toxicity outside controlled environments.

The segment concludes that leveraging both clinical and real-world evidence ensures more accurate expectations of treatment benefit, helping clinicians individualize therapy and monitor outcomes in diverse practice settings.

Panelists discuss how real-world data complement clinical trials in understanding outcomes for ALK-positive lung cancer.

Using Long-Term Data to Guide ALK+ NSCLC Treatment

Panelists explain that long-term results have redefined expectations for disease control, guiding decisions about sequencing and treatment duration. They highlight that deep responses and intracranial protection achieved with newer inhibitors have shifted clinical priorities toward maintaining therapy adherence and minimizing toxicity.

The discussion emphasizes shared decision-making between clinicians and patients. By aligning treatment goals with patient preferences and tolerability, care teams can improve adherence and sustain treatment benefits over time.

Overall, panelists agree that integrating long-term outcomes data into practice helps clinicians anticipate patterns of resistance, personalize follow-up, and design durable treatment strategies that align with evolving patient needs.

Panelists discuss how mature survival data inform treatment sequencing and maintenance strategies in ALK-positive lung cancer.

Investigational Therapies and Ongoing Trials in ROS1+ NSCLC

Panelists explore the growing pipeline of investigational therapies that address limitations of currently approved ROS1 inhibitors. These include agents designed to overcome common resistance mutations and to provide improved brain penetration. Early clinical studies have demonstrated encouraging activity in patients who have progressed on prior targeted therapy.

They stress the importance of biomarker-driven clinical trial enrollment, which ensures appropriate matching between patient profiles and therapeutic targets. The development of next-generation inhibitors represents a critical step toward managing acquired resistance, which remains a major challenge in this disease subset.

The panel concludes that ongoing research efforts, including global collaborations, are critical for expanding the armamentarium against ROS1-positive lung cancer and ensuring continued progress toward durable disease control and improved patient outcomes.

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

Use of ROS1-Targeting Agents in Clinical Practice

Panelists highlight how real-world experience mirrors clinical trial outcomes, demonstrating substantial benefits with targeted therapy when patients are appropriately selected through molecular testing. They emphasize that early testing is essential to avoid delays in initiating treatment and ensuring optimal response.

Challenges in real-world implementation include limited access to next-generation sequencing and variations in testing quality across institutions. Panelists discuss how multidisciplinary collaboration and patient education can mitigate these disparities. They also emphasize the importance of proactive monitoring for toxicity and adherence support.

Ultimately, they agree that the translation of evidence-based ROS1 therapy into community practice requires standardized molecular testing, strong communication across care teams, and ongoing evaluation of outcomes to guide continuous improvement in care delivery.

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

ALK Alterations and Treatment Options for ALK+ NSCLC

 gene fusions and how they have reshaped the treatment landscape for a distinct subset of lung cancer patients. They describe how these rearrangements activate cell proliferation pathways, leading to aggressive tumor growth if left untreated. Targeted therapy development has resulted in significant survival improvements, particularly with newer agents capable of addressing central nervous system disease.

The discussion highlights that treatment selection in the first-line setting now requires consideration of central nervous system penetration, resistance coverage, and toxicity profile. The panel emphasizes that continuous innovation in ALK inhibition has set a precedent for precision medicine in lung cancer.

In summary, panelists note that the evolution of ALK-targeted therapy exemplifies how scientific discovery translates into meaningful clinical benefit, allowing patients to achieve prolonged survival and improved quality of life.

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

Long-Term Data in ALK+ NSCLC

Panelists review long-term follow-up from pivotal studies showing that durable responses are possible with contemporary targeted therapies. They highlight sustained progression-free survival and intracranial control, demonstrating that many patients now live for years with stable disease.

They also address safety considerations, noting that most adverse effects are manageable with dose modifications and supportive care. The ability to maintain therapy over extended periods without significant toxicity has improved patient quality of life and overall outcomes.

The conversation concludes that long-term data reinforce confidence in the use of next-generation inhibitors as first-line therapy, validating the importance of precision targeting and early intervention for ALK-positive lung cancer.

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

Spotlight on ROS1-Targeted Therapies in Advanced NSCLC

Panelists begin by outlining the biological significance of 

 rearrangements in a small subset of non–small cell lung cancer (NSCLC). They explain that these alterations drive oncogenic signaling through constitutive activation of cellular growth pathways. This subset typically occurs in younger patients and those without a history of smoking. Identifying such fusions accurately is crucial for optimal patient management.

The panel highlights that comprehensive molecular testing—particularly RNA-based sequencing—has become essential for detecting these rearrangements and differentiating them from other oncogenic drivers. Panelists also note that the availability of broad next-generation sequencing panels has improved diagnostic efficiency, especially in cases with limited tissue.

Overall, they emphasize that understanding the biology, epidemiology, and molecular underpinnings of ROS1-positive disease allows clinicians to implement a more targeted and effective therapeutic approach, marking a significant step forward in precision oncology.

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

Treatment Options for ROS1+ Advanced NSCLC

Panelists describe how targeted therapy has become the standard of care for patients with ROS1-positive disease. They discuss the evolution of selective inhibitors, which have demonstrated improvements in systemic and intracranial efficacy compared with earlier therapies. Treatment choice now requires balancing efficacy, safety, and central nervous system activity.

The conversation emphasizes how durability of response and tolerability are crucial in determining therapy selection. Long-term disease control often hinges on maintaining continuous exposure to therapy, requiring careful management of adverse events. Panelists also highlight the value of assessing patient-specific factors such as comorbidities and access to ongoing monitoring.

They conclude by noting that the field continues to advance rapidly, with new generations of inhibitors showing promise for overcoming resistance and improving intracranial outcomes. The integration of molecular retesting at disease progression will further refine individualized treatment strategies.

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

Lorenza Landi, MD

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