Decision-Making Factors in Choosing Combination Therapies in EGFR-Mutated NSCLC

Opinion
Video

Panelists discuss how the growing role of combination therapies in EGFR-mutated non–small cell lung cancer (NSCLC) influences the choice between the MARIPOSA and FLAURA2 trials, considering overall survival data, multidisciplinary implementation, patient education, and their impact on first-line prescribing decisions.

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Comparing MARIPOSA vs FLAURA2 in EGFR-Mutated NSCLC: Implementation Guide

Key Decision Factors Between MARIPOSA and FLAURA2

  • Data Maturity: MARIPOSA has a clear advantage in data generation and maturity compared with FLAURA2.
  • Overall Survival (OS): MARIPOSA shows compelling OS data with an HR of 0.79 (upper confidence limit 1.02) and curves separating at later time points.
  • Brain Metastases: Both regimens show promising brain activity, as follows:
    • MARIPOSA demonstrates 36% of patients remain brain metastasis-free at 3 years vs only 18% with monotherapy.
  • Intracranial duration of response shows stabilization until 2 years, then a clear separation of curves.
  • A 6-month benefit in intracranial durability was shown with combination therapy.

Impact of OS Data on Decision-Making

  • OS data strongly supports using combination therapy over monotherapy.
  • Physicians emphasized using the best therapy first because there's approximately 30% attrition between therapy lines.
  • The plateau in survival curves, particularly for brain metastasis prevention, is clinically meaningful.

Implementation in Practice

Multidisciplinary Approach

  • Team Education: Sharing data with the entire team (including infusion nurses and patient education nurses)
  • Dermatology Collaboration: Essential to have dermatologists who understand these trials
    • Teleconsultation option: "I can send a picture over to my dermatologist, and he or she will send you back exactly what to do"
  • Psychiatry Support: May be needed for some patients experiencing adverse effects

Patient Education

  • Discussing Options: Taking time to explain the complexity of choices
  • Patient-Centered Approach
  • Managing Expectations: Preparation for potential adverse effects and their management

Expected Changes in Prescribing Patterns

  • Movement away from single-agent osimertinib toward combination approaches
  • Need for physician experience
  • Recognition that with experience comes knowledge
  • Opportunity to tailor treatment to individual patient needs with 2 strong options
  • Real-world data will further inform optimal usage.

Future Directions

  • Need for real-world prospective data collection to optimize:
    • Treatment duration
    • Combination strategies
    • Adverse effect management

Importance of biomarker work to better understand mechanisms of brain protection

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