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NSCLC survival longer in females vs males

Jackey Suen
28 Sep 2018
Dr Kathy Albain

Female patients with non-small-cell lung cancer (NSCLC) have markedly better survival than male NSCLC patients, according to the SWOG S0424 study presented at the International Association for the Study of Lung Cancer’s 19th World Conference on Lung Cancer (WCLC 2018).

“Importantly, the better survival in female NSCLC patients could not be explained by treatment differences or any other analysis or model,” highlighted lead investigator Dr Kathy Albain of Loyola University Chicago Stritch School of Medicine, Chicago, Illinois, US. “Our study results suggest that future randomized controlled trials on NSCLC should stratify patients by sex.”

The prospective SWOG S0424 study evaluated 957 patients newly diagnosed with stage I–III NSCLC, who were grouped into four cohorts based on sex and smoking history (female ever-smokers, n=337; male ever-smokers, n=383; female never-smokers, n=188; male never-smokers, n=49). [Albain KS, et al, WCLC 2018, abstract OA06.01]

“Retrospective studies have reported sex difference in NSCLC and its interaction with smoking status, inherited susceptibility, carcinogen metabolism, environmental exposures, tumour stage/histology/biology, sex hormone influences, and survival,” explained Albain. “The SWOG S0424 study is the first prospective report of overall survival [OS], including modelling of survival with multiple significant parameters.”

Results showed that the estimated 5-year OS rate was 73 percent for female non-smokers, 69 percent for female ever-smokers, 58 percent for male never-smokers, and 52 percent for male ever-smokers. Female patients were found to have significantly better OS rate than male patients after adjusting for smoking history, lifestyle factors, disease stage, treatment, tumour biology, and hormonal factors.

Tumours in female patients were also found to have higher frequency of EGFR mutations (odds ratio [OR], 2.13; p=0.009) and lower frequency of p53 mutations (OR, 0.65; p=0.02). EGFR mutations were more common in Asian vs Caucasian patients (OR, 3.46; p=0.003) and in adenocarcinoma vs squamous histology (OR, 3.5; p=0.009), but were less common in ever-smokers (OR, 0.17; p<0.001) and patients with higher BMI (OR, 0.95; p=0.046). KRAS mutations and p53 mutations were more frequent in ever-smokers (OR, 5.06 and 3.38, respectively; both p<0.001).

In multivariate analysis, female, large-cell histology, high BMI, greater height, and presence of EGFR mutations were significantly associated with better OS. In contrast, more advanced age, stage II/III disease, presence of p53 mutation, and higher expression of oestrogen receptor (ER)-α and ER-β were significantly associated with worse OS.

“Despite adjustments for every factor that might influence survival in NSCLC, female NSCLC patients in our study lived longer than their male counterparts. This could not be explained by any analysis or model,” concluded Albain.

“The study is large and well-executed. The results corroborate previous findings, including the different frequency of common mutations between Asians and Caucasians,” said invited discussant Dr Valerie Rusch of the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, US. “The study also demonstrated the persistent OS difference in female vs male NSCLC patients. Sex should always be stratified when designing future trials for resectable NSCLC.”

“Further investigations should be conducted to understand sex hormone influences and the underlying biological mechanisms that may explain the survival differences among males and females,” she added.

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