Inferior Survival Outcomes Revealed in African American Patients with EGFR-Mutant NSCLC

August 27, 2020

This is the first report to date that has demonstrated inferior survival outcomes among African American patients with NSCLC harboring an EGFR mutation relative to non-African American patients.

African American patients with EGFR-mutant non–small cell lung cancer (NSCLC) had significantly shorter survival compared with non-African American patients, according to a report on survival disparities in this patient population.

This is the first report to date that has demonstrated inferior survival outcomes among African American patients with NSCLC harboring an EGFR mutation relative to non-African American patients, suggesting an unmet need for more customized treatment approaches of this patient population.

To evaluate these disparities among African American patients with NSCLC harboring EGFR mutations, investigators retrospectively reviewed individual patient cases from a New York-Bronz (Montefiore) network cancer registry database of patients diagnosed from January 1, 2009, to December 31, 2015. Approximately 2773 cases were diagnosed during this time period, and 1986 patients were diagnosed with nonsquamous NSCLC. However, 636 of these patients were not included due to a lack of pathology reports., and 698 were excluded due to a lack of EGFR mutational status.

A total of 656 patients with available pathology and EGFR mutational status were included in the study. EGFRmutations occured at a rate of 15% in all patients, 14% in African Americans, and 16% in non-African American patients. Del 19, L858R, and uncommon mutations, respectively, occur in 46%, 23%, and 31% of African American patients versus 43%, 35%, and 22% in non-African American Patients, but no significant difference was observed between the 2 groups (P =.39).

The overall response rate was 63.6% among African American patients versus 76.0% in non-African American patients (P =.454), and the 2-year survival rate was 38.2% versus 39% among those with EGFR wild-type patients. Among those with EGFR mutations, the difference in the 2-year survival rates varied dramatically between African Americans (33.3%) and non-African Americans (61.3%). Multivariate regression models that were adjusted for gender, age, smoking status, weight, and stage had similar racial differences in survival for EGFR wild-type (P =.774) and EGFR-mutant patients (P =.001).

The survival difference was significant, despite a limited sample size, with uncommon EGFR mutations among African American and non-African American patients (P =.008).A trend was also observed for shorter survival in African Americans with common EGFR mutations (P =.074). The survival disparity, however, was particularly evident in earlier stages of disease, including stage I-III (P =.001) and in those with metastatic disease or stage IV disease (P =.044).

The recurrence rate was 40% in the African American population versus 47% in the non-African American population, which was noted as similar. African American patients had a significant inferior survival among patients with metastatic disease with common EGFR mutations who received EGFR TKIs per standard practice at that time (P =.040), in which the 2-year survival rate was 44.4% compared with 77.3% in non-African Americans.

When investigators stratified patients with EGFR mutations by gender, non-African American females had significantly favorable survival (P =.049), but African American women did not survive longer compared with their male counterparts. This finding was consistent with previous studies that have reported women with lung cancer having favorable survival outcomes compared with male counterparts.

Unlike the del 19 and L858R mutations, uncommon EGFR mutations are considered a heterogenous group with diverse genetic compositions and varied responses to EGFR tyrosine kinase inhibitors (TKIs).

In non-African American patients, 6 (43%) had mutations that were likely sensitive to FDA-approved EGFR TKIs, including G719A in exon 18 (n = 3), E709K and G719A in exon 18 (n = 1), Q701L and G719A in exon 18 (n = 1), G719S in exon 18 and S768I in exon 20 (n = 1). Eight patients (57%) had likely resistant mutations, which included H773_V774insHPH in exon 20 (n = 1), H773dup in exon 20 (n = 1), N771_P772insH in exon 20 (n = 1), S768_D770dupSVD in exon 20 (n = 3), N771, H773 dupNPH in exon 20 (n = 1), and D770_N771insG in exon 20 (n = 1).

Among the African American population in this study who had uncommon EGFR mutations, 4 (36%) had likely sensitive mutations, including G719A in exon 18 and L861Q in exon 21 (n = 1), L858R in exon 21 and S768I in exon 20 (n = 1), G719A in exon 18 and S768I in exon 20 (n = 1), and L747_P753del7insS in exon 19 and L833V in exon 21 (n = 1). Three patients (27%) had likely resistant mutations, which included N771_H773dupNPH in exon 20 (n = 1), P772_H773insGHP in exon 20 (n= 1), and A763_Y764ins4 in exon 20 (n = 1). In addition, 4 patients (36%) had undetermined or controversial sensitivity of mutations, including L833F in exon 21 (n = 1), H773L and V774M in exon 20 (n = 1), and S768I and V769L in exon 20 (n = 2).

In respect to age at diagnosis, gender, presenting stages, and socioeconomic status, the patient characteristics between the 2 groups were similar, but there was a significant weight difference between the African American and non-African American patients harboring uncommon and common EGFR mutations (75.1 kg vs. 65.6 kg; P =.012). The weight difference, however, was not observed in EGFR wild-type patients. There was also no significant difference in terms of exposure to EGFR TKIs in the African American patients (51%) and non-African American patients (49%; P =.42). A weight difference was observed among African American versus non-African Americans harboring common EGFR mutations (78.4 kg vs. 65.1 kg; P =.0051), but the difference was insignificant in terms of the uses of EGFR TKIs (P =.40) among those with metastatic NSCLC with common EGFR mutations. There was also no difference in terms of frontline EGFR TKI use (P=.57).

Reference

Cheng H, Hosgood HD, Deng L, et al. Survival disparities in black patients with EGFR-mutated non-small cell lung cancer. Clinical Lung Cancer. 2020 21:2, 177-185. doi: 10.1016/j.cllc.2019.07.003