Researchers have identified differences in tumor characteristics that may help explain sex- and race-based disparities in patients with metastatic non-small cell lung cancer (NSCLC).1
The data showed that women were more likely than men to be diagnosed with metastatic NSCLC, but women were also more likely to have actionable mutations and tended to have longer overall survival (OS).
Most actionable mutations were similarly distributed across racial and ethnic groups. However, Asian patients were more likely to have EGFR mutations and less likely to have KRAS mutations. Tumor mutation burden was highest in Black patients.
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These study results were presented at the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved by David Qian, MD, PhD, of Emory University in Atlanta.
For this study, Dr Qian and colleagues used the MSK-MET database, which included data on 25,775 patients with 50 tumor types and 99,419 metastases.
The researchers focused only on the 4710 patients with metastatic NSCLC. Most patients (86%) had adenocarcinoma, 58% were women, and the median age at diagnosis was 67 years. Patients self-identified as non-Hispanic White (76%), Asian (10%), Black (5%), Hispanic (4%), Native American (1%), or none of the above (1%). Smoking status and treatment history were unavailable.
Compared with non-Hispanic patients, Hispanic patients were more likely to be diagnosed with metastatic NSCLC prior to the age of 50 (18% vs 7%, P <.001).
Women were more likely than men to be diagnosed with metastatic NSCLC, regardless of race or ethnicity. However, the median OS was longer for women than for men — 42 months and 26 months, respectively (HR, 0.69; 95% CI, 0.63-0.75; P <.0001).
The proportion of men without actionable mutations was almost twice as high as the proportion of women without actionable mutations (29% and 16%, respectively; P <.0001).
Higher tumor mutation burden was associated with inferior OS (HR, 1.14; 95% CI, 1.10-1.19; P <.0001). Black patients were more likely to have a high tumor mutation burden than non-Black patients (9% and 5%, respectively, with ≥20 mutations per Mb; P =.019).
Asian patients had a higher frequency of EGFR mutations than non-Asian patients (56% and 22%, respectively; P <.0001). Asian patients also had a lower frequency of KRAS mutations (11% vs 32%; P <.0001).
Independent Predictors of OS
In multivariable analysis, there was no significant difference in OS across racial or ethnic groups.
However, there was a difference in OS by sex. Women had a significantly lower risk of death than men (HR, 0.74; 95% CI, 0.68-0.81; P <.001).
Histology was also associated with OS. The risk of death was higher for patients with large-cell carcinoma (HR, 1.39; 95% CI, 1.07-1.80; P =.013) or squamous cell carcinoma (HR, 1.26; 95% CI, 1.09-1.45; P =.002), compared with adenocarcinoma.
Age at diagnosis was associated with OS as well. An increased risk of death was seen in patients who were younger than 50 years of age at diagnosis (hazard ratio [HR], 1.38; 95% CI, 1.16-1.63; P <.001) or older than 70 years at diagnosis (HR, 1.19; 95% CI, 1.08-1.30; P <.001), when compared with patients diagnosed at 50-70 years of age.
The presence of targetable mutations was associated with superior OS in some cases. The HR was 0.77 for EGFR mutations (P <.001), 0.72 for ALK mutations (P =.001), 0.82 for MET mutations (P =.049), and 0.79 for RET mutations (P =.040). There was no significant association for NTRK, BRAF, or KRAS mutations.
Implications for Practice
Since Hispanic patients were more likely to be diagnosed with NSCLC prior to age 50, and diagnosis before age 50 is associated with worse OS, Dr Qian suggested that lung cancer screening should start at an earlier age for Hispanic patients with risk factors.
Dr Qian speculated that the differences between men and women in the frequency of metastatic NSCLC diagnoses and the proportion of cases with actionable mutations are likely attributable to different sex-associated tumor biology.
The differences may also be related to sex differences in carcinogen metabolism. Research has suggested that factors other than tobacco use may account for approximately 15% of lung cancer cases in women and 10% in men.2 Therefore, Dr Qian suggested that regulatory agencies might consider environmental exposures beyond cigarette smoking in the recommendations for performing screening CT scans.
Although high tumor mutation burden has been linked to better outcomes with immunotherapy,3 high tumor mutation burden was associated with worse outcomes in the current study.1 Dr Qian recommended improving access to next-generation sequencing across patient subgroups.
This retrospective analysis of prospectively collected patients could have been biased in unintended, unrecognized ways, Dr Qian acknowledged. There were important variables, including smoking history, other exposures, and treatment history, that were not available. For these reasons, verification and additional study are warranted before clinical application or regulatory changes are implemented.
Nonetheless, Dr Qian’s study suggests that precision diagnostics and data analysis could help refine the treatment for metastatic NSCLC across age, sex, and racial/ethnic groups.
Disclosures: Dr Qian reported having no disclosures.
References
1. Qian DC, Steuer CE, Tian S, et al. Landscape of actionable mutations and outcomes in metastatic non-small cell lung cancer across age, sex, and race. Presented at AACR Disparities 2022. September 16-19, 2022. Abstract PR008.
2. Jemal A, Miller KD, Ma J, et al. Higher lung cancer incidence in young women than young men in the United States. N Engl J Med. 2018;378(21):1999-2009. doi:10.1056/NEJMoa1715907
3. Ricciuti B, Wang X, Alessi JV, et al. Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels. JAMA Oncol. 2022;8(8):1160-1168. doi:10.1001/jamaoncol.2022.1981
