The American Society of Clinical Oncology (ASCO) is committed to developing dynamic guidelines for specific topic areas that continuously evolve with new research and evidence, resulting in frequent changes in recommended clinical practices. These living guidelines are regularly updated by a standing expert panel that systematically reviews health literature on an ongoing basis. In 2022, ASCO introduced living clinical practice guidelines for systemic therapy in patients with stage IV non-small cell lung cancer (NSCLC), both with and without driver alterations. These guidelines have recently been updated to reflect the latest advancements in the field.

Today, we will delve into the updated living guideline from May 2024, focusing on Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations. The expert panel reviewed new evidence from seven studies that met the systematic review inclusion criteria and approved the updated recommendations. We will explore the key takeaways and insights surrounding the latest update. Please note that this list does not cover all major points. For a comprehensive list of recommendations, please refer to the full text of the living guideline update or the pocket guide.

Key Takeaways and Recommendations:
  • Targeted Therapy as First-Line:
    • For patients with identified driver mutations (e.g., EGFR, ALK, ROS1), targeted therapies remain the first-line treatment. Osimertinib is the preferred option for EGFR mutations.
  • New Driver Alterations:
    • The guidelines now include recommendations for emerging targets like MET and RET, reflecting the evolving landscape of molecular profiling in NSCLC.
  • Combination Therapy Strategies:
    • Research into combining targeted therapies with immunotherapy is ongoing, aiming to improve treatment outcomes and manage resistance.
  • Resistance Management:
    • Novel strategies for overcoming acquired resistance to targeted therapies, such as next-generation TKIs and combination approaches, are being highlighted. Given the emergence of potentially targetable resistance mechanisms, it is imperative to diligently assess for the presence of new mutations through tissue and/or NGS testing.
  • Clinical Trial Participation:
    • Patients are encouraged to actively engage in clinical trials in order to gain access to cutting-edge treatments and to contribute to the advancement of research. ASCO firmly believes that cancer clinical trials play a crucial role in shaping medical decisions and enhancing the quality of cancer care. Therefore, it is essential that all patients are given the opportunity to participate in these trials.
  • Palliative Care Integration:
    • Early integration of palliative care is recommended to improve symptom management and overall quality of life for patients with advanced lung cancer. It is crucial that these patients are referred to interdisciplinary palliative care teams for consultation, who can provide both inpatient and outpatient care at the onset of their disease, in conjunction with their cancer treatment. This approach ensures that patients receive comprehensive support and care throughout their treatment journey.

These revised guidelines showcase the latest advancements in the treatment of Stage IV NSCLC, with a specific emphasis on personalized approaches that are customized to individual genetic profiles. We appreciate your participation in our Guidelines Spotlight. Please don’t hesitate to share your feedback with us. We are excited to present our next spotlight to you soon!

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