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.