Symptomatic androgen deficiency and sexual dysfunctions in male patients receiving alectinib for ALK‐positive advanced non–small cell lung cancer.

Background: It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK‐positive cancer and in murine models. Methods: In this study, three groups, including an experimental group of male patients with ALK‐positive, advanced non–small cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK‐positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK‐negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist. Results: Ninety‐five patients were consecutively enrolled onto the study. Among sixty‐eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p =.0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p =.0002) were significantly lower in ALK‐positive ANSCLC patients in cohort A compared with ALK‐negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p =.0059) and LH levels (4.72 vs. 7.49 mUI/ml; p =.0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK‐positive male patients (74.3 vs. 44.24 pg/ml; p =.0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B. Conclusions: Symptoms of androgen deficiency should be tracked in male patients with ALK‐positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate. Male patients with ALK‐positive advanced non–small cell lung cancer treated with first‐line alectinib had lower median total testosterone (p =.0001) and free testosterone (p =.0002) levels compared with male patients who had ALK‐negative disease and were receiving other anticancer treatments. Symptoms of hypogonadism were more frequent in ALK‐positive patients compared with ALK‐negative patients (62% vs 26.8% rates of positive score at ADAM questionnaire, respectively), suggesting the need for hormone assessment and referral to an andrologist, as appropriate. [ABSTRACT FROM AUTHOR]