EGFR-mutated mNSCLC: Sharing Clinical Insights and Best Practices - Episode 5
Choosing the Most Effective Frontline Treatment to Account for Patient Attrition
Experts discuss a key finding from FLAURA2 showing that many patients never reach second-line therapy, reinforcing the importance of delivering the most effective treatment—such as combination therapy—up-front, particularly when patients are fit, as real-world barriers and rapid progression may limit later opportunities for intervention.
The panel highlighted a key insight from the FLAURA2 data showing that approximately 30% of patients in both treatment arms never received second-line therapy following disease progression. This finding, though initially surprising to many clinicians, was acknowledged as likely reflective of real-world clinical practice—even among highly motivated patients enrolled in clinical trials. The reality that a significant portion of patients may not reach second-line treatment reinforces the importance of delivering the most effective therapy up-front when possible.
This has direct implications for treatment decisions. Given the risk that a patient may never receive subsequent therapy, clinicians are increasingly considering combination therapy with osimertinib and chemotherapy as the preferred first-line approach. The rationale is clear: mMaximize therapeutic impact when the patient is well enough to tolerate treatment. While individual patient preferences and tolerability remain critical to decision-making, the potential to achieve longer survival through a more aggressive initial strategy is compelling, particularly in light of the survival benefit demonstrated in FLAURA2.
Still, the panel acknowledged that practice patterns and outcomes can vary across different settings. Access to care, regional treatment norms, and patient characteristics can all influence whether patients ultimately receive second-line therapy. Some clinicians pointed out that global trial data may not fully reflect experiences in U.S.-based academic centers, where second-line access might be higher. However, the consistent drop-off rates across multiple studies support the broader concern that disease progression can often be rapid and unmanageable, leaving little opportunity for follow-up treatment. This underscores the shift in thinking toward using the most effective combinations earlier in the disease course, especially when patients are fit and treatment options are fully accessible.
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