Abstract
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. In this study, three groups, including an experimental group of male patients with ALK-positive, advanced nonsmall 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. 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. 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.
Overview
- The study investigates the effects of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) on hormone levels in male patients with ALK-positive, advanced nonsmall cell lung cancer (ANSCLC) and in murine models. The study compares the outcomes observed in an experimental group of male patients with ALK-positive 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). The study aims to answer the question of whether ALK-positive ANSCLC patients who receive alectinib experience hypogonadism and to determine the impact of alectinib on hormone levels in male patients with ALK-positive ANSCLC. The study uses a prospective design and 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. The study enrolled 95 patients consecutively. The primary objective of the study is to determine the impact of alectinib on hormone levels in male patients with ALK-positive ANSCLC.
Comparative Analysis & Findings
- The study found that 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. The study found that ALK-positive ANSCLC patients who receive alectinib experience hypogonadism, and testosterone replacement should be considered, as appropriate.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice. The study highlights the need to track symptoms of androgen deficiency in male patients with ALK-positive ANSCLC who are receiving alectinib and to consider testosterone replacement, as appropriate. The study also identifies the need for further research to investigate the long-term effects of alectinib on hormone levels and to determine the optimal dosing and duration of treatment. The study suggests that future research should focus on developing and testing interventions to prevent or mitigate the effects of alectinib-induced hypogonadism in male patients with ALK-positive ANSCLC. The study also highlights the importance of monitoring hormone levels in male patients with ALK-positive ANSCLC and the need for clinicians to be aware of the potential for hypogonadism in this population. The study's findings have important implications for the management of male patients with ALK-positive ANSCLC and highlight the need for further research to optimize the management of this population.