Initial ribociclib plus endocrine therapy for HR+/HER2- advanced breast cancer in pre- and postmenopausal Chinese women: Primary results from a phase 2 randomized study.

BACKGROUND: The MONALEESA­7 and ­2 phase 3 randomized trials demonstrated a statistically significant progression­free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre­ and postmenopausal patients with hormone receptor­positive (HR+)/human epidermal growth factor receptor 2­negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre­ and postmenopausal patients with HR+/HER2­ ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA­7 and ­2 studies. METHODS: Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator­assessed PFS. RESULTS: As of April 25, 2022, the median follow­up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies. CONCLUSIONS: These data demonstrate a favorable benefit­risk profile for ribociclib + ET in Chinese patients.

Apalutamide and Goserelin for Androgen Receptor-Positive Salivary Gland Carcinoma: A Phase II Nonrandomized Clinical Trial, YATAGARASU.

PURPOSE: To assess the efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive unresectable or recurrent/metastatic salivary gland carcinoma. PATIENTS AND METHODS: This trial was an open-label, single-arm, multicenter phase II study. Patients with histologically confirmed unresectable or recurrent/metastatic salivary gland carcinoma with AR expression were included. The primary endpoint was the overall response rate (ORR) according to RECIST v1.1 by an independent central radiology review in the first 24 response-evaluable (RE) patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded. RESULTS: A total of 31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by independent central radiology review was 25.0% [6/24 patients; 95% confidence interval, 9.8%-46.7%; P = 0.11 (one-sided)], which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR positivity ≥70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain. CONCLUSIONS: Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive salivary gland carcinoma and safety consistent with prior experience in prostate cancer.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Cost-Effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in the Treatment of Patients With Metastatic Prostate Cancer: A Societal Perspective.

OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.

Análise de custo-utilidade da gosserrelina no tratamento de pacientes com leiomioma: uma perspectiva do Sistema Único de Saúde / Cost-utility analysis of goserelin in the treatment of patients with leiomyoma: a perspective from the Unified Health System

Objetivos: Gosserrelina é indicada para mulheres com leiomioma, por reduzir o risco associado às complicações clínicas. Este trabalho realizou uma análise de custo-utilidade comparando o uso e o não uso de gosserrelina em pacientes com leiomioma sob a perspectiva do Sistema Único de Saúde. Métodos: Um modelo de árvore de decisão foi estruturado para reproduzir o impacto clínico e econômico do uso de gosserrelina antes da miomectomia, cujo comparador seria o não uso de gosserrelina em pacientes elegíveis. Foram considerados: custos médicos diretos e eventos clínicos como complicações intra-hospitalares e tempo de internação. A razão de custo-utilidade incremental é representada pelo custo incremental da gosserrelina por anos de vida ajustado pela qualidade (QALY). Resultados: Em um cenário em que o acesso à gosserrelina é de 51% das pacientes, o custo incremental foi de R$ 629,08. Pacientes no grupo gosserrelina apresentaram um incremento de 0,0261 no QALY. A razão de custo-utilidade incremental foi de R$ 24.019,26 por QALY, ficando abaixo do limiar adotado pelo Ministério da Saúde. Ao variar o percentual de pacientes que recebem gosserrelina para 80% antes de um procedimento cirúrgico, houve um aumento de QALY para 0,5013, reduzindo custos de complicações e a razão de custo-utilidade incremental para R$ 10.581,07 por QALY. No cenário em que 100% das pacientes utilizam gosserrelina, há um aumento de QALY para 0,8290, reduzindo custos de complicações e a razão de custo-utilidade incremental para R$ 10.288,28 por QALY. Conclusão: O uso de gosserrelina possui custo-utilidade favorável, considerando os parâmetros utilizados nesta modelagem econômica. Quando o acesso à gosserrelina é maior, há um decremento expressivo no custo por QALY.

Objectives: Goserelin is indicated for women with leiomyoma to reduce the risk associated with clinical complications. This study conducted a cost-utility analysis comparing the use and non-use of goserelin in patients with leiomyoma from the perspective of the Brazilian Unified Health System. Methods: A decision tree model was structured to reproduce the clinical and economic impact of using goserelin before myomectomy, compared to not using it in eligible patients. Direct medical costs and clinical events such as in-hospital complications and length of stay were considered. The incremental cost-utility ratio is represented by the incremental cost of goserelin per quality-adjusted life year (QALY). Results: In a scenario where access to goserelin is 51% of patients, the incremental cost was R$ 629.08. Patients in the goserelin group showed an increase of 0.0261 in QALY. The incremental cost-utility ratio was R$ 24,019.26 per QALY, below the threshold adopted by the Ministry of Health. When the percentage of patients receiving goserelin was increased to 80% before surgery, there was an increase in QALY to 0.5013, reducing complication costs and the incremental cost-utility ratio to R$ 10,581.07 per QALY. In the scenario where 100% of patients use goserelin, QALY increased to 0.8290, reducing complication costs and the incremental cost-utility ratio to R$ 10,288.28 per QALY. Conclusions: The use of goserelin has a favorable cost utility, considering the parameters used in this economic modeling. When access to goserelin is higher, there is a significant decrease in the cost per QALY.

Ribociclib plus Endocrine Therapy in Early Breast Cancer.

BACKGROUND: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear. METHODS: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy. RESULTS: As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals. CONCLUSIONS: Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.).

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Clinical analysis of acute postoperative pain after total laparoscopic hysterectomy for adenomyosis and uterine fibroids - a prospective observational study.

OBJECTIVE: To investigate the outcome of total laparoscopic hysterectomy (TLH) and postoperative pain characteristics and compare the pain severity after TLH for adenomyosis or uterine fibroids. METHODS: This prospective observational study collected 101 patients received TLH for adenomyosis (AD group) including 41 patients were injected goserelin (3.6 mg) 28 days before TLH, while other adenomyosis patients received TLH without preoperative treatment, and 113 patients received TLH for uterine fibroids (UF group). Pain scores were evaluated at different time sites from operation day to postoperative 72 h using the numeric rating scale. Clinical data were collected from clinical record. RESULTS: Operative time and anaesthetic time were longer in the AD group than those in the UF group (66.88 ± 8.65 vs. 64.46 ± 7.21, p = 0.04; 83.95 ± 10.05 vs. 79.77 ± 6.88, p < 0.01), severe endometriosis was quite more common in AD group (23.76% vs. 2.65%, p < 0.01). Postoperative usage of Flurbiprofen in AD group were more than that of UF group (15.48 ± 38.00 vs. 4.79 ± 18.16, p = 0.02). Total pains and abdominal visceral pains of AD group were more severe compared with UF group in motion and rest pattern at several time sites, while incision pain and shoulder pain were similar. The total postoperative pains after goserelin preoperative treatment in AD group were less than that without goserelin preoperative treatment (p < 0.05). The levels of serum NPY, PGE2 and NGF after laparoscopic hysterectomy of adenomyosis reduced with GnRH agonist pretreatment. CONCLUSIONS: Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids. While patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids.Patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

N-glycans from serum IgG and total serum glycoproteins specific for endometriosis.

Endometriosis is a chronic inflammatory gynaecological disease characterized by the growth of endometrial tissue outside the uterine cavity. There are currently no definitive non-invasive diagnostic tools. Glycosylation is the most common posttranslational modification of proteins and altered glycosylation has been found in many diseases, including chronic inflammatory conditions and cancer. Sialylation and galactosylation on serum IgG have previously been found to be altered in endometriosis and serum sialylation changed after Zoladex (Goserelin Acetate) therapy. Using IgG and whole serum glycoproteins, we investigated N-glycosylation in two clinical cohorts of women with and without endometriosis. PNGase F-digested serum samples were fluorescently labelled and N-glycans were profiled by ultra-performance liquid chromatography. Clinical data was collected to link glycomic findings with metabolic and hormonal profiles. Total serum glycoprotein and IgG glycosylation differed in patients with endometriosis compared to control cases. The most significantly altered was glycan peak 3 from IgG, containing bisected biantennary glycans, which was decreased in the endometriosis cohorts (p = 0.0000005-0.018). In conclusion, this is the first pilot study to identify changes in N-glycans from whole serum glycoproteins associated with endometriosis. A larger validation study is now warranted and such studies should include the follow-up of surgically and pharmacologically treated patients.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

Erythema nodosum caused by goserelin acetate sustained-release: Case report and literature review.

Goserelin acetate is a gonadotropin-releasing hormone analog that is commonly used in patients with prostate cancer, endometriosis, and precocious puberty. The side effects of the drug include allergic rash, flushing, excessive sweating, skin swelling at the injection site, sexual dysfunction, erectile dysfunction, and menopausal symptoms. However, erythema nodosum has so far not been reported. In this paper, we have presented the case of erythema nodosum caused by goserelin acetate and a review of the literature on its adverse effects, thus providing useful insights into clinical management and medication safety.

Whole exon capture sequencing for identifying mutations associated with pulmonary benign metastasising leiomyoma.

A woman in her early 20s presented with cough and fever. She had undergone an abdominal myomectomy 3 years ago for uterine leiomyoma. Chest CT and positron emission tomography-CT revealed multiple round nodules in both lungs, suggesting metastatic lesions. A CT-guided lung biopsy was performed, and the tumour was diagnosed as pulmonary benign metastasising leiomyoma (PBML) based on pathological analyses. Whole exon capture sequencing of uterine leiomyoma and PBML sections revealed that 13 genes (MCM10, SLC16A9, RAG1, BAZ1A, NLRP2, TRMT61B, CPXM1, NGLY1, SUCLG2, FAM13A, CAGE1, PHTF2 and ZDHHC2) were concurrently present in the two tumours. The patient was prescribed goserelin injections every 4 weeks. The symptoms improved 2 weeks after starting the treatment. The lung nodules considerably decreased in size after three courses of goserelin treatment. The nodular size continues to decrease with the treatment.

Comparison of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer.

PURPOSE: Although different gonadotropin-releasing hormone (GnRH) agonists may have different effects, their effect of ovarian protection during chemotherapy for breast cancer has not been compared. This study aimed to compare the effects of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer. METHODS: This prospective study analyzed 193 patients with breast cancer aged ≤ 40 years who had regular menstruation and serum anti-Müllerian hormone (AMH) levels ≥ 1 ng/mL before treatment. Patients received either goserelin or leuprorelin for ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy. Resumption of menstruation and changes in serum levels of AMH were compared between the two groups at 12 months after completion of chemotherapy. RESULTS: The mean age and the pretreatment serum AMH level were 33.2 years and 4.4 ng/mL in goserelin group and 34.2 years and 4.0 ng/mL in leuprorelin group. The proportion of patients who resumed menstruation was not different between the goserelin (94.4%) and leuprorelin (95.3%) groups at 12 months after chemotherapy completion. Serum AMH levels decreased significantly in both the goserelin (from 4.4 to 1.2 ng/mL) and leuprorelin (from 4.0 to 1.2 ng/mL) groups, with no statistical significance. In addition, no difference was found in the proportion of patients with serum AMH levels ≥ 1 ng/mL between the goserelin (49.5%) and leuprorelin (44.2%) groups at 12 months after chemotherapy. CONCLUSION: Goserelin and leuprorelin were comparable in terms of ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy in young patients with breast cancer.

Cardiovascular adverse events-related to GnRH agonists and GnRH antagonists: analysis of real-life data from Eudra-Vigilance and Food and Drug Administration databases entries.

INTRODUCTION AND OBJECTIVES: GnRH agonists and GnRH antagonists are two of the mainstays of hormonal therapy (HT) for prostate cancer (PCa). These drugs are at increased risk of cardiovascular (CV) adverse events (AEs). Aim of our study was to compare real-life data on AEs associated with GnRH agonists and GnRH antagonists based on Eudra-Vigilance (EV) and Food and Drug Administration (FDA) reported AEs. MATERIALS AND METHODS: EV and FDA databases were queried and the number of CV adverse events (AEs) for degarelix, buserelin, goserelin, leuprorelin, triptorelin until September 2021 were recorded. Specific CV AEs were recorded and data were analyzed per age and severity. pooled relative risk (PRR) was used to compare data between drugs. RESULTS: CV events were reported in 315/5128 (6%) for Degarelix, in 55/628 for Buserelin (9%), in 843/12,145 (7%) for Goserelin, in 3395/71,160 (5%) for Leuprorelin and in 214/4969 (5%) for Triptorelin. In terms of specific CV disorders, Degarelix presented lower risk of hypertension (PRR 0.60 (95% CI 0.37-0.98), p = 0.04), of myocardial infarction (PRR 0.05 (95% CI 0.01-0.39), p < 0.01) and thrombosis (PRR 0.14 (0.02-1.07), p = 0.06) when compared to GnRH agonists. Overall, younger patients (<65 years) presented a very low risk of CV AEs. Side effects were classified as serious in 90-96% of the cases. Fatal AEs were 5-20% over the CV AEs and 0.2-1% over the total AEs. CONCLUSIONS: Real-life data are consistent with registry studies regarding side effects related to HT. Real-life data suggest GnRH agonists are associated with higher CV AEs when compared to GnRH antagonists. Clinicians should consider these data when prescribing HT especially in patients with CV comorbidities.

Systematic risk analysis of radiation pneumonitis in breast cancer: role of cotreatment with chemo-, endocrine, and targeted therapy.

PURPOSE: A major complication of sequential and concomitant chemoradiation in breast cancer treatment is interstitial pneumonitis induced by radiation therapy (RT), systemic therapy, or a combination of both. Dose and volume of co-irradiated lung tissue directly correlate with the risk of radiation pneumonitis. Especially in case of combined treatment, it is often unclear which of the used therapeutic agents promote pneumonitis. METHODS: This was a prospective monocentric study including 396 breast cancer patients. A systematic analysis of single and combined therapeutic measures was performed in order to identify treatment-related factors enhancing the risk of pneumonitis post RT. RESULTS: Overall incidence of pneumonitis of any grade was 38%; 28% were asymptomatic (grade 1) and 10% were symptomatic (> grade 1). Pneumonitis > grade 2 did not occur. Beside age, smoking status, and mean lung dose, the combined treatment with goserelin and tamoxifen significantly enhanced the risk of pneumonitis in a supra-additive pattern (odds ratio [OR] 4.38), whereas each agent alone or combined with other drugs only nonsignificantly contributed to a higher pneumonitis incidence post RT (OR 1.52 and OR 1.16, respectively). None of the other systemic treatments, including taxanes, increased radiation pneumonitis risk in sequential chemoradiation. CONCLUSION: Common treatment schedules in sequential chemoradiation following breast-conserving surgery only moderately increase lung toxicity, mainly as an asymptomatic complication, or to a minor extent, as transient pneumonitis ≤ grade 2. However, combined treatment with tamoxifen and the LHRH analog goserelin significantly increased the risk of pneumonitis in breast cancer patients after chemoradiation. Thus, closer surveillance of involved patients is advisable.

Clinical efficacy and safety of trimonthly administration of goserelin acetate 10.8 mg in premenopausal Chinese females with symptomatic adenomyosis: a prospective cohort study.

OBJECTIVE: This prospective cohort study aimed to compare the clinical efficacy and safety of goserelin 10.8 mg administered trimonthly with goserelin 3.6 mg administered monthly in premenopausal females with symptomatic adenomyosis. METHODS: We recruited 139 premenopausal females with adenomyosis who complained of dysmenorrhea and/or menorrhagia. The first group (n = 70) received a single subcutaneous injection of goserelin 10.8 mg, and the second group (n = 69) received monthly subcutaneous goserelin 3.6 mg administered for 3 months. Follow-up was performed at the outpatient department after 12 weeks. RESULTS: Ultimately, 130 patients completed the study, including 68 and 62 patients in the goserelin 10.8 mg (n = 70) and 3.6 mg (n = 69) groups, respectively. We observed a significant decrease in the dysmenorrhea (NRS) score, uterine volume, and cancer antigen 125 (CA125) levels, and a significant increase in hemoglobin (HGB) levels in both treatment groups. There was no significant difference between the two groups. The sum of the adverse event scores was slightly higher in the goserelin 3.6 mg than in the 10.8 mg group. CONCLUSIONS: The clinical efficacy of trimonthly administration of goserelin 10.8 mg was equivalent to monthly 3.6 mg dosing and was non-inferior regarding safety and tolerability. Hence, it can be a more cost-effective and convenient alternative treatment option in premenopausal females with symptomatic adenomyosis. TRIAL REGISTRATION: ChiCTR2200059548.

Analysis of adverse event of interstitial lung disease in men with prostate cancer receiving hormone therapy using the Food and Drug Administration Adverse Event Reporting System.

AIMS: To investigate interstitial lung disease (ILD) in men with prostate cancer receiving hormone therapy. METHODS: We gathered cases diagnosed with prostate cancer based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2020. We divided the included cases into 3 groups based on the primary suspected drugs: a hormone therapy group, a positive control group (taxanes), and a negative control group. We employed reporting odds ratio, a disproportionality method, to detect the association between ILD events and target drugs. RESULTS: We finally included a total of 85 403 cases, 69 894 cases (628 ILD event cases) in the hormone therapy group, 2302 cases (158 ILD event cases) in the positive control group and 13 207 cases (72 ILD event cases) in the negative control group. There were 394 ILD event cases (62.74%) in the hormone therapy group in Japan; 78.68% of the ILD events occurred within the first year after hormone treatment. Disproportionality analysis indicated that ILD events were significantly associated with nilutamide, flutamide, bicalutamide, goserelin, degarelix and apalutamide; the reporting odds ratios (95% confidence interval) were 32.14 (11.03-93.63), 9.93 (3.62-27.21), 8.19 (6.01-11.16), 3.74 (2.61-5.37), 2.41 (1.55-3.75) and 1.94 (1.01-3.75), respectively. CONCLUSION: Based on this FAERS pharmacovigilance analysis, the association between ILD events and hormone therapy drugs, including bicalutamide, flutamide, nilutamide, goserelin, degarelix and apalutamide, should not be ignored, especially in the Japanese population. Lung function of prostate cancer patients should be monitored when receiving the hormone therapy drugs mentioned above, especially for the first year post medication.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Gene expression analysis in endometriosis: Immunopathology insights, transcription factors and therapeutic targets.

Background: Endometriosis is recognized as an estrogen-dependent inflammation disorder, estimated to affect 8%-15% of women of childbearing age. Currently, the etiology and pathogenesis of endometriosis are not completely clear. Underlying mechanism for endometriosis is still under debate and needs further exploration. The involvement of transcription factors and immune mediations may be involved in the pathophysiological process of endometriosis, but the specific mechanism remains to be explored. This study aims to investigate the underlying molecular mechanisms in endometriosis. Methods: The gene expression profile of endometriosis was obtained from the gene expression omnibus (GEO) database. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were applied to the endometriosis GSE7305 datasets. Cibersort and MCP-counter were used to explore the immune response gene sets, immune response pathway, and immune environment. Differentially expressed genes (DEGs) were identified and screened. Common biological pathways were being investigated using the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Transcription factors were from The Human Transcription Factors. The least absolute shrinkage and selection operator (Lasso) model identified four differential expressions of transcription factors (AEBP1, HOXB6, KLF2, and RORB). Their diagnostic value was calculated by receiver operating characteristic (ROC) curve analysis and validated in the validation cohort (GSE11691, GSE23339). By constructing the interaction network of crucial transcription factors, weighted gene coexpression network analysis (WGCNA) was used to search for key module genes. Metascape was used for enrichment analysis of essential module genes and obtained HOXB6, KLF2. The HOXB6 and KLF2 were further verified as the only two intersection genes according to Support Vector Machine Recursive Feature Elimination (SVM-RFE) and random forest models. We constructed ceRNA (lncRNA-miRNA-mRNA) networks with four potential transcription factors. Finally, we performed molecular docking for goserelin and dienogest with four transcription factors (AEBP1, HOXB6, KLF2, and RORB) to screen potential drug targets. Results: Immune and metabolic pathways were enriched in GSVA and GSEA. In single sample gene set enrichment analysis (ssGSEA), most immune infiltrating cells, immune response gene sets, and immune response pathways are differentially expressed between endometriosis and non-endometriosis. Twenty-seven transcription factors were screened from differentially expressed genes. Most of the twenty-seven transcription factors were correlated with immune infiltrating cells, immune response gene sets and immune response pathways. Furthermore, Adipocyte enhancer binding protein 1 (AEBP1), Homeobox B6 (HOXB6), Kruppel Like Factor 2 (KLF2) and RAR Related Orphan Receptor B (RORB) were selected out from twenty-seven transcription factors. ROC analysis showed that the four genes had a high diagnostic value for endometriosis. In addition, KLF2 and HOXB6 were found to play particularly important roles in multiple modules (String, WGCNA, SVM-RFE, random forest) on the gene interaction network. Using the ceRNA network, we found that NEAT1 may regulate the expressions of AEBP1, HOXB6 and RORB, while X Inactive Specific Transcript (XIST) may control the expressions of HOXB6, RORB and KLF2. Finally, we found that goserelin and dienogest may be potential drugs to regulate AEBP1, HOXB6, KLF2 and RORB through molecular docking. Conclusions: AEBP1, HOXB6, KLF2, and RORB may be potential biomarkers for endometriosis. Two of them, KLF2 and HOXB6, are critical molecules in the gene interaction network of endometriosis. Discovered by molecular docking, AEBP1, HOXB6, KLF2, and RORB are targets for goserelin and dienogest.