Symptomatic androgen deficiency and sexual dysfunctions in male patients receiving alectinib for ALK-positive advanced nonsmall cell lung cancer

Emanuele Vita; Federico Monaca; Domenico Milardi; Luca Mastrantoni; Alessio Stefani; Edoardo Vergani; Jacopo Russo; Diletta Barone; Ileana Sparagna; Antonio Vitale; Alessandro Scala; Denis Occhipinti; Mariantonietta Di Salvatore; Alfredo Pontecorvi; Giampaolo Tortora; Emilio Bria

doi:10.1002/cncr.35293

Symptomatic androgen deficiency and sexual dysfunctions in male patients receiving alectinib for ALK-positive advanced nonsmall cell lung cancer

Cancer. 2024 Mar 28. doi: 10.1002/cncr.35293. Online ahead of print.

Authors

Emanuele Vita¹, Federico Monaca², Domenico Milardi³, Luca Mastrantoni², Alessio Stefani², Edoardo Vergani³, Jacopo Russo², Diletta Barone², Ileana Sparagna², Antonio Vitale², Alessandro Scala², Denis Occhipinti², Mariantonietta Di Salvatore¹, Alfredo Pontecorvi³, Giampaolo Tortora², Emilio Bria¹

Affiliations

¹ UOSD Oncologia Toraco-Polmonare, Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
² UOC Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
³ UOC di Medicina Interna, Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

PMID: 38549441
DOI: 10.1002/cncr.35293

Abstract

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 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.

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.

Keywords: alectinib; anaplastic lymphoma kinase (ALK); hypogonadism; nonsmall cell lung cancer (NSCLC).

Abstract

Grants and funding