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

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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