Long-Term Benefit With First-Line Osimertinib Monotherapy in EGFR-Mutated Advanced NSCLC in the Era of Intensified First-Line Therapy.

INTRODUCTION: First-line osimertinib monotherapy remains a standard treatment for advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), although intensified regimens improve outcomes at the cost of an increased toxicity and treatment burden. We characterized pretreatment clinical features associated with a long-term benefit (LTB) and developed an exploratory clinical score. METHODS: This retrospective cohort comprised patients receiving first-line osimertinib monotherapy for advanced or recurrent EGFR-mutated NSCLC at 25 Japanese institutions between September 2018 and March 2022. An LTB was defined as both progression-free survival (PFS) ≥24 months and overall survival (OS) ≥48 months, based on the FLAURA2 trial. Factors associated with an LTB were evaluated using multivariable logistic regression. Six independently associated favorable factors were each assigned a score of 1 if present, yielding an exploratory 0-6-point score. RESULTS: Among 803 included patients, 204 (25.4%) experienced an LTB. The six independently associated factors were age <75 years, an Eastern Cooperative Oncology Group performance status of 0-1, a serum albumin level ≥3.5 g/dL, postoperative recurrence, EGFR exon 19 deletion, and the absence of liver metastasis. LTB rates were 2.5%, 19.0%, and 50.7% in the 0-2-, 3-4-, and 5-6-point groups, respectively (P for trend<0.001). The median PFS was 7.2, 16.8, and 30.5 months, and the median OS was 12.7, 35.9, and 68.3 months, respectively. CONCLUSIONS: This exploratory score may support prognostic stratification regarding the likelihood of durable outcomes with osimertinib monotherapy but does not establish whether monotherapy should be preferred over an intensified regimen.