Factors Associated With Long-Term Survivors With Epidermal Growth Factor Receptor Positive Non-Small Cell Lung Cancer...

In East-Asian predominant populations, multiple reports identify East-Asian ancestry as prognostic of improved outcome in EGFRmut⁺ non-small cell lung cancer (NSCLC) populations when treated with first/second generation tyrosine kinase inhibitor (TKI). Generalizability to more heterogeneous populations is less understood.

To identify clinical characteristics associated with long-term survival (LTS) in patients from heterogeneous Canadian populations with advanced NSCLC with EGFRmut⁺ treated with first-line TKIs.

De novo advanced EGFRmut⁺ NSCLC diagnoses receiving a first/second generation epidermal growth factor receptor-TKI between 2004 and 2016 were included. Demographic, clinical, treatment, and outcome details were extracted from three sources: two province-wide, multi-center registries, the Alberta Glans-Look Lung Cancer Research Database (GLR), and the British Columbia Cancer (BCC), along with data from Princess Margaret Cancer Center (PM), a single-center, urban, tertiary hospital. Survival time from TKI initiation was divided into LTS, patients surviving longer than the upper quartile (34.4 months), and the remaining patients described as 'non-long-term survivors' (non-LTS).

Of 577 patients (GLR: 246, PM: 112, and BCC: 219), median overall survival was 20.3 months. From initiation of TKI, LTS-median survival was 48.5 months, whereas non-LTS was 15.7 months. The LTS cohort differed significantly from non-LTS in many clinical and pathologic characteristics, including being significantly more likely to be of East-Asian ancestry (50% vs. 39%, p = 0.02), Female (74% vs. 64%, p = 0.04), and more likely to harbor exon19del-mutation (60% vs. 46%, p = 0.004). In multivariate analysis, exon19del (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.63-0.93, p = 0.01) and East-Asian ethnicity (HR = 0.75, 95% CI 0.69-0.94, p = 0.02) were independently associated with longer survival. Male sex (HR = 1.36, 95% CI 1.12-1.66, p < 0.01) was associated with shorter survival, while smoking status, treatment site, and age > 70 years were not independent prognostic factors.

This study confirmed previously known prognosticators within a real-world multicenter Canadian cohort. This included East-Asian ancestry, female sex, and exon19del, which were associated with better overall survival. Future work to better understand the impact of socioeconomic factors and biological reasons for ancestry resulting in different prognosis are needed to better guide treatment management.