First-line Osimertinib for Poor Performance Status Patients With EGFR Mutation-positive Non-small Cell Lung Cancer: A Prospective Observational Study

Abstract

Objective: The clinical outcomes of poor performance status (PS) patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive EGFR mutations.Materials and Methods: We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered osimertinib (80 mg/day) as the initial treatment.Results: Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78 years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred. Conclusion: Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies with larger cohorts are warranted.

Retrospective analysis of independent predictors of progression‐free survival in patients with EGFR mutation‐positive advanced non‐small cell lung cancer receiving first‐line osimertinib

“…However, the FLAURA study reported that osimertinib is less toxic than first‐generation EGFR‐TKIs, and osimertinib has been administered to patients with poor PS in the real‐world. A phase II trial using gefitinib as first‐line therapy in patients with poor PS reported a PS improvement rate of 79% (90% CI: 67–92), 28 while a prospective study using osimertinib reported a PS improvement rate of 50% (CI: unknown) 31 . In patients with positive T790M mutation after disease progression, using osimertinib as a second‐line therapy after treatment with first‐generation EGFR‐TKIs is reported to have a potential survival advantage over using osimertinib as first‐line therapy 32 .…”

“…A phase II trial using gefitinib as first‐line therapy in patients with poor PS reported a PS improvement rate of 79% (90% CI: 67–92), 28 while a prospective study using osimertinib reported a PS improvement rate of 50% (CI: unknown). 31 In patients with positive T790M mutation after disease progression, using osimertinib as a second‐line therapy after treatment with first‐generation EGFR‐TKIs is reported to have a potential survival advantage over using osimertinib as first‐line therapy. 32 Based on these findings, the use of gefitinib, which is expected to improve PS in the first‐line setting, may be preferred for patients with poor PS, followed by the use of osimertinib when the T790M mutation becomes positive after PD onset.…”