Cancer-treatment cohort finds a survival gap between men and women
A retrospective international study found longer survival among men receiving enfortumab vedotin for metastatic urothelial cancer. An analysis of separate tumor samples also found higher expression of the drug’s NECTIN-4 target in men. The findings connect clinical and molecular differences without establishing a causal mechanism, and the authors call for prospective studies that include sex as a variable.
Science··Midday
Patient outcomes diverged
A peer-reviewed international analysis found that men treated with enfortumab vedotin for metastatic urothelial cancer lived longer than women in the same retrospective cohort. The drug belongs to the antibody–drug conjugate family: an antibody recognizes a target on cancer cells and carries a cytotoxic drug. The investigators paired a comparison of patient outcomes with a separate analysis of the molecular target, NECTIN-4.[1], [2]
The clinical cohort comprised 454 people, including 365 men and 89 women. Median follow-up was 13.2 months. Median overall survival reached 13.6 months in men and 7.7 months in women; time on treatment was 13.3 and 7.4 months respectively. Women more often had disease progression at the first imaging assessment during treatment, the study’s definition of primary resistance. These outcomes describe patients who received the drug, with no randomized allocation between the sexes.[1]
Tumor targets differed in separate samples
To examine the drug target, Tarek Taha, Ithai Waldhorn and their colleagues turned to The Cancer Genome Atlas, a database of tumor molecular information. NECTIN-4 expression was higher in male tumors, and the difference persisted after accounting for molecular subtype. Smoking status and estrogen-response pathways were also associated with expression patterns. The target was not measured in the clinical cohort’s own tumors, so these molecular observations cannot establish a causal link with the survival difference.[1], [2]
After adjustment for prespecified clinical variables, female sex remained associated with poorer survival. The adjusted hazard ratio was 1.75, with a 95 percent confidence interval of 1.26–2.42. Adding smoking status did not materially change the estimate. The tumor database largely represented localized disease, whereas the treated cohort had metastatic cancer. Socioeconomic information was unavailable, and the exploratory analyses had no overall adjustment for multiple comparisons.[1]
Patients received enfortumab vedotin alone
Enfortumab vedotin has established activity in advanced urothelial cancer, both alone and with immunotherapy. The present analysis concerned single-drug outcomes; combination regimens are a separate clinical setting. The authors recommend incorporating sex into prospective antibody–drug conjugate research. Their observational findings generate hypotheses for future work rather than measuring how much absolute benefit each sex receives compared with another treatment.[1], [2]
