Abstract
Background
The CHART study demonstrated that rezvilutamide plus androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) versus bicalutamide plus ADT in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC), with an acceptable safety profile. This post hoc analysis evaluates the impact of hepatotoxicity and lipid metabolism–related toxicity (LMRT) on long-term survival and quality of life (QoL) in this population.
Methods
Data from 323 patients with high-volume mHSPC who received rezvilutamide plus ADT were analyzed. Hepatotoxicity was defined as elevations in γ-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, or bilirubin, whereas LMRT included hypertriglyceridemia, hypercholesterolemia, and weight gain. All P values were nominal.
Results
Any-grade hepatotoxicity and LMRT occurred in 24.6% (79/323) and 56.7% (183/323) of patients, respectively. No significant differences in rPFS (hazard ratio [HR], 0.716; 95% confidence interval [CI], 0.434–1.181; P = 0.1908), OS (HR, 0.890; 95% CI, 0.532–1.489; P = 0.6569), or QoL were observed between patients with and without hepatotoxicity. In contrast, patients who developed LMRT showed longer rPFS (HR, 0.594; 95% CI, 0.400–0.883; P = 0.0100) and OS (HR, 0.594; 95% CI, 0.383–0.922; P = 0.0201) than those without LMRT. Patients experiencing grade ≥3 LMRT demonstrated greater improvements in QoL scores from baseline.
Conclusions
This is the first study to evaluate the association of hepatotoxicity and LMRT with clinical outcomes in patients with high-volume mHSPC treated with rezvilutamide plus ADT. Hepatotoxicity was not significantly associated with survival or QoL, whereas LMRT was associated with prolonged rPFS and OS, and grade ≥3 LMRT was associated with more pronounced improvements in QoL.
Trial registration:
ClinicalTrials.gov, NCT03520478.
Keywords: Hepatic toxicity, Lipid metabolism–related toxicity, Post hoc analysis, Quality of life, Rezvilutamide, Survival outcomes
Background
Prostate cancer is one of the most common malignancies worldwide, ranking second in incidence and fifth in mortality among male cancers [1]. Although the incidence of prostate cancer in China remains lower than that in Europe and the United States, it is projected to continue increasing [2]. Novel endocrine therapies in combination with androgen deprivation therapy (ADT) have become standard treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC) [3]. Among the adverse events associated with these therapies are hepatotoxicity and lipid metabolism–related toxicity [4–7].
Previous studies have suggested that liver function parameters, such as γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin, as well as lipid metabolism–related indicators, including triglycerides, total cholesterol, and body weight, may serve as potential biomarkers for predicting the development and progression of prostate cancer [8–13]. However, the associations between these biomarkers and prostate cancer appear to be influenced by multiple factors [8, 14]. Moreover, in patients receiving novel endocrine therapies, the impact of alterations in these parameters on treatment efficacy and quality of life (QoL) remains unclear.
Rezvilutamide is a novel oral androgen receptor (AR) inhibitor. The CHART study, a multicenter, randomized, open-label, phase III trial conducted at 72 hospitals across China, Poland, the Czech Republic, and Bulgaria, compared rezvilutamide plus ADT with bicalutamide plus ADT in patients with high-volume mHSPC [4]. The results demonstrated that rezvilutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) while maintaining an acceptable safety profile. Based on these findings, rezvilutamide has been approved by the National Medical Products Administration in China for the treatment of patients with high-volume mHSPC [15].
This post hoc analysis was conducted to assess the impact of hepatotoxicity and lipid metabolism–related toxicity on survival outcomes and QoL in patients with high-volume mHSPC receiving rezvilutamide.
Methods
Study design and ethical approval
The CHART trial was an international, multicenter, randomized, open-label, active-controlled, phase III study (ClinicalTrials.gov identifier: NCT03520478) conducted between June 28, 2018, and August 6, 2020, at 72 hospitals in China, Poland, the Czech Republic, and Bulgaria [4]. The study was carried out in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The protocol and all amendments were approved by the Fudan University Shanghai Cancer Center Institutional Review Board (approval number: 1802181-1) and the independent ethics committees of all participating institutions. Written informed consent was obtained from all patients before initiation of study treatment.
Study population
Eligible patients were men aged ≥18 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 and histologically or cytologically confirmed prostate adenocarcinoma without evidence of neuroendocrine differentiation or small-cell carcinoma. Patients were required to have high-volume disease, defined as ≥4 bone metastases on technetium-99m bone scan with at least one lesion outside the pelvis or spine, or visceral metastases (excluding lymph node involvement) detected on computed tomography (CT) or magnetic resonance imaging (MRI). All patients were planned to initiate or continue ADT and were either unable to tolerate or unwilling to receive chemotherapy. Full inclusion and exclusion criteria are provided in the previously published literature [4].
Procedures
Eligible patients were randomized to receive either rezvilutamide or bicalutamide, both in combination with ADT. This post hoc analysis included only patients treated with rezvilutamide plus ADT. Rezvilutamide was administered orally at a dose of 240 mg once daily in 28-day cycles and continued until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision to discontinue treatment. Background therapy, including surgical castration or administration of luteinizing hormone–releasing hormone agonists or antagonists, was maintained according to the product label. Dose interruptions and reductions of rezvilutamide were permitted, with up to two dose reductions (first to 160 mg and then to 80 mg). Additional details regarding dose modifications are provided in the CHART study protocol [4].
Assessments
Radiographic evaluations were conducted by both the Independent Review Committee and investigators at baseline, on day 1 of cycle 5, and on day 1 of every 4 cycles thereafter until 30 days after the last dose. CT or MRI assessments were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, whereas bone scans were evaluated using the modified Prostate Cancer Working Group 3 (PCWG3). QoL was assessed at baseline, on day 1 of each cycle from cycles 2–12, every 2 cycles from cycles 13–36, every 4 cycles thereafter, and 30 days after the last dose. Health-related QoL (HRQoL) was measured using the Functional Assessment of Cancer Therapy–Prostate (FACT-P, version 4). Adverse events were monitored continuously during treatment and up to 30 days after the last dose and were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03. For each patient, only the highest grade of each adverse event was recorded. Additional safety assessments included vital signs, physical examinations, and laboratory tests, conducted at baseline, on day 15 of cycle 1, on day 1 of each cycle from cycles 2–12, every 2 cycles from cycles 13–36, every 4 cycles thereafter, and 30 days after the last dose.
Outcomes
The primary endpoints of the CHART study were rPFS, assessed by the Independent Review Committee, and OS in the intention-to-treat population. rPFS was defined as the time from randomization to the first documented radiographic progression or death from any cause, whichever occurred first. OS was defined as the time from randomization to death from any cause. Radiographic progression included progression of soft-tissue lesions on CT or MRI (per RECIST criteria) or progression of bone lesions on bone scan (per modified PCWG3 criteria). Secondary endpoints included investigator-assessed rPFS and safety. HRQoL, measured using the FACT-P (version 4), was included as an exploratory endpoint.
Statistical analysis
Efficacy analyses were based on the intention-to-treat population, defined as all randomized patients. Safety analyses included all patients who received at least one dose of study drug. Median rPFS and OS were estimated using the Kaplan–Meier method, with 95% confidence intervals (CIs) calculated by the Brookmeyer–Crowley method. Hazard ratios (HRs) and corresponding 95% CIs for between-group comparisons were estimated using an unstratified Cox proportional hazards model. The incidence and severity of hepatotoxicity and lipid metabolism–related toxicity were summarized descriptively and graded according to the NCI-CTCAE (version 4.03). Changes from baseline in QoL measures, including FACT-P total score, Functional Assessment of Cancer Therapy-General (FACT-G) total score, and the Trial Outcome Index (TOI), were reported as least-squares means with standard errors (SE). As this was a post hoc analysis of the CHART study, no prespecified hypothesis testing was performed; therefore, all P values are nominal. Statistical analyses were performed using SAS software, version 9.4.
Results
Patients
Between June 28, 2018, and August 6, 2020, a total of 654 patients were enrolled, of whom 326 were randomized to receive rezvilutamide plus ADT. Among these, two patients withdrew before initiating treatment; two patients randomized to the rezvilutamide group actually received bicalutamide and were included in the bicalutamide group for the safety analysis; and one patient randomized to the bicalutamide group received rezvilutamide and was included in the rezvilutamide group for the safety analysis. Accordingly, 323 patients were included in the safety analysis set. Baseline characteristics of the rezvilutamide plus ADT group have been reported previously [4]. The median age was 69 years (interquartile range [IQR], 64–74), with 48% of patients aged ≥70 years, and the majority (90%) were Asian. An ECOG performance status of 1 was observed in 74% of patients. The baseline characteristics of patients with or without hepatotoxicity and those with or without lipid metabolism–related toxicity are presented in Additional file 1: Table S1 and Additional file 1: Table S2, respectively.
Treatment-related hepatotoxicity and lipid metabolism–related toxicity
Among patients receiving rezvilutamide plus ADT, the incidence of any-grade hepatotoxicity was 24.6% (79/323), including elevations in GGT (6.2%), AST (20.1%), ALT (19.2%), abnormal liver function (0.9%), and bilirubin (1.2%). The incidence of grade ≥3 hepatotoxicity was 4.0% (13/323). Any-grade lipid metabolism–related toxicity occurred in 56.7% (183/323), comprising hypertriglyceridemia (27.9%), hypercholesterolemia (18.9%), and weight gain (46.7%). The incidence of grade ≥3 lipid metabolism–related toxicity was 9.6% (31/323) (Table 1).
Table 1.
Treatment-related hepatotoxicity and lipid metabolism–related toxicity
| Events, n (%) | Rezvilutamide plus ADT (n = 323) | |
|---|---|---|
| Any grade | Grade ≥3 | |
| Hepatotoxicity | 79 (24.6%) | 13 (4.0%) |
| γ-Glutamyl transferase increased | 20 (6.2%) | 3 (0.9%) |
| Aspartate aminotransferase increased | 65 (20.1%) | 7 (2.2%) |
| Alanine aminotransferase increased | 62 (19.2%) | 7 (2.2%) |
| Abnormal liver function | 3 (0.9%) | 3 (0.9%) |
| Blood bilirubin increased | 4 (1.2%) | 1 (0.3%) |
| Lipid metabolism–related toxicity | 183 (56.7%) | 31 (9.6%) |
| Hypertriglyceridemia | 90 (27.9%) | 15 (4.6%) |
| Hypercholesterolemia | 61 (18.9%) | 0 |
| Weight gain | 151 (46.7%) | 16 (5.0%) |
ADT, androgen deprivation therapy
Impact of hepatotoxicity on survival outcomes and QoL
As of February 28, 2022, the median follow-up was 33.15 months (95% CI, 32.30–35.15) for patients who developed hepatotoxicity and 33.02 months (95% CI, 31.28–33.22) for those without hepatotoxicity. Median rPFS was not reached (NR) in either group (95% CI, NR–NR for patients with hepatotoxicity; 95% CI, 39.75–NR for those without), with no statistically significant difference observed (HR, 0.716; 95% CI, 0.434–1.181; P = 0.1908) (Fig. 1A). Similarly, OS did not differ significantly between patients with and without hepatotoxicity (HR, 0.890; 95% CI, 0.532–1.489; P = 0.6569) (Fig. 1B). No significant differences in rPFS or OS were observed between patients with grade ≥3 hepatotoxicity and those without (Additional file 2: Fig. S1). QoL outcomes, including FACT-G, FACT-P, and TOI scores, also showed no significant differences between patients with and without hepatotoxicity (Fig. 2) or between those with and without grade ≥3 hepatotoxicity (Additional file 2: Fig. S2). The median duration of rezvilutamide treatment was 30.09 months (IQR 19.55, 36.90) in patients with hepatotoxicity versus 28.48 months (IQR 15.61, 34.96) in those without (Additional file 1: Table S3). Among patients with hepatotoxicity, dose reductions, interruptions, and discontinuations due to drug-related adverse events occurred in 6.3%, 3.8%, and 2.5% of patients, respectively, whereas these events were not reported in patients without hepatotoxicity (Additional file 1: Table S3).
Fig. 1.
Association of hepatotoxicity with survival outcomes. (A) Radiographic progression-free survival; (B) Overall survival. CI, confidence interval; NR, not reached; HR, hazard ratio
Fig. 2.
Association of hepatotoxicity with quality-of-life outcomes. (A) FACT-G; (B) FACT-P; (C) TOI. FACT-G, Functional Assessment of Cancer Therapy-General; FACT-P, Functional Assessment of Cancer Therapy-Prostate; TOI, Trial Outcome Index; SE, standard errors
Impact of lipid metabolism–related toxicity on survival outcomes and QoL
As of February 28, 2022, the median follow-up was 33.15 months (95% CI, 31.87–33.25) for patients who developed lipid metabolism–related toxicity and 33.08 months (95% CI, 30.46–33.22) for those without. Patients who experienced lipid metabolism–related toxicity had significantly longer rPFS than those without (NR [95% CI, NR–NR] vs. NR [95% CI, 29.57–NR]; HR, 0.594; 95% CI, 0.400–0.883; P = 0.0100) (Fig. 3A). Median OS was NR in either group (95% CI, NR–NR); however, OS was significantly longer in patients with lipid metabolism–related toxicity compared with those without (HR, 0.594; 95% CI, 0.383–0.922; P = 0.0201) (Fig. 3B). No significant differences in rPFS or OS were observed between patients with grade ≥3 lipid metabolism–related toxicity and those without (Fig. 4). QoL scores did not differ significantly between patients with and without lipid metabolism–related toxicity (Fig. 5); however, patients who developed grade ≥3 lipid metabolism–related toxicity exhibited greater improvements in QoL scores relative to baseline, including FACT-G, FACT-P, and TOI scores (Fig. 6). The median duration of rezvilutamide treatment was 30.55 months (IQR 22.67, 36.90) in patients with lipid metabolism–related toxicity versus 26.32 months (IQR 12.42, 34.43) in those without (Additional file 1: Table S4). Among patients with lipid metabolism–related toxicity, dose reductions, interruptions, and discontinuations due to drug-related adverse events occurred in 0.5%, 0.5%, and 0% of patients, respectively, compared with 2.9%, 1.4%, and 1.4% in patients without lipid metabolism–related toxicity (Additional file 1: Table S4).
Fig. 3.
Association of lipid metabolism–related toxicity with survival outcomes. (A) Radiographic progression-free survival; (B) Overall survival. CI, confidence interval; NR, not reached; HR, hazard ratio
Fig. 4.
Association of grade ≥3 lipid metabolism–related toxicity with survival outcomes. (A) Radiographic progression-free survival; (B) Overall survival. CI, confidence interval; NR, not reached; HR, hazard ratio
Fig. 5.
Association of lipid metabolism–related toxicity with quality-of-life outcomes. (A) FACT-G; (B) FACT-P; (C) TOI. FACT-G, Functional Assessment of Cancer Therapy-General; FACT-P, Functional Assessment of Cancer Therapy-Prostate; TOI, Trial Outcome Index; SE, standard errors
Fig. 6.
Association of grade ≥3 lipid metabolism–related toxicity with quality-of-life outcomes. (A) FACT-G; (B) FACT-P; (C) TOI. FACT-G, Functional Assessment of Cancer Therapy-General; FACT-P, Functional Assessment of Cancer Therapy-Prostate; TOI, Trial Outcome Index; SE, standard errors
Discussion
The CHART study established rezvilutamide plus ADT as a preferred treatment option for patients with high-volume mHSPC [4, 15]. This post hoc analysis is the first to evaluate the association of hepatotoxicity and lipid metabolism–related toxicity with long-term survival outcomes and QoL in this population. Our findings indicate that rPFS, OS, and QoL scores were not significantly affected by the occurrence of hepatotoxicity. In contrast, patients who developed lipid metabolism–related toxicity experienced significantly longer rPFS and OS, and those with grade ≥3 lipid metabolism–related toxicity demonstrated greater improvements in QoL scores compared with patients without grade ≥3 events.
Prostate cancer is highly dependent on androgen signaling, with excessive activation of the AR recognized as a key driver of tumor initiation and progression [16]. Beyond its canonical role in transcriptional regulation, AR also contributes to metabolic reprogramming, promoting tumor growth through pathways such as oxidative phosphorylation and lipogenesis [17]. Rezvilutamide, a potent AR antagonist, competitively blocks androgen binding, thereby inhibiting AR nuclear translocation, DNA binding, and AR-mediated transcription [15, 18]. Inhibition of AR signaling disrupts the regulation of intracellular and systemic lipid metabolism, predisposing patients to dyslipidemia. In parallel, ADT lowers circulating testosterone levels, which not only weakens the inhibitory effect of androgens on stem cell differentiation into adipocytes but also reduces adipocyte lipolysis and attenuates androgen-mediated suppression of triglyceride synthesis from free fatty acids. Together, these mechanisms promote weight gain, fat accumulation, and lipid metabolism–related adverse events [19, 20]. Lipid metabolism–related toxicity is therefore among the most common adverse effects associated with ADT and/or second-generation AR inhibitors in clinical practice [21–24]. In the CHART study, the incidence of any-grade lipid metabolism–related toxicity reached 56.7% in patients treated with rezvilutamide plus ADT.
Our results suggest that patients who developed lipid metabolism–related abnormalities had longer PFS and OS compared with those without such events. Weight gain is a common lipid metabolism–related toxicity associated with second-generation AR inhibitors [23–25]. However, the prognostic significance of obesity or weight changes in prostate cancer remains uncertain. Retrospective analyses in non-metastatic disease have shown that pre-diagnosis obesity or post-diagnosis weight gain increases the risk of cardiovascular-specific and all-cause mortality, but has little effect on prostate cancer–specific mortality [26]. Another study found that pre-diagnosis weight gain was not associated with prostate cancer incidence or all-cause mortality [27]. By contrast, in patients with mHSPC, higher baseline BMI has been identified as a predictor of improved treatment response and survival [28]. Similarly, in metastatic castration-resistant prostate cancer, obese patients demonstrated longer overall and cancer-specific survival compared with those who were overweight or of normal weight [29]. One possible explanation is that obesity or weight gain may mitigate cancer-related cachexia, thereby improving tolerance and responsiveness to systemic therapy and ultimately contributing to better clinical outcomes [28–30].
Unlike other second-generation AR inhibitors such as apalutamide, darolutamide, and enzalutamide [23–25], the lipid metabolism–related abnormalities observed in the CHART study were not limited to weight gain but also included hypertriglyceridemia and hypercholesterolemia. Dysregulated lipid metabolism may affect tumor biology by altering nutrient availability and redox balance within the tumor microenvironment, thereby modulating energy metabolism and growth signaling pathways and indirectly influencing tumor progression and survival [31–33]. Triglycerides are a major component of the blood lipid profile. Evidence indicates that triglyceride levels are significantly associated with serum total testosterone, bioavailable testosterone, sex hormone–binding globulin, and androgen levels, all of which are integral to the initiation, progression, and maintenance of prostate cancer, suggesting a potential role for triglycerides in prostate cancer development [34]. However, studies examining the association between serum triglyceride levels and prostate cancer risk have yielded inconsistent results [34–37]. In terms of prognosis, some investigations have shown that in patients with clinically localized prostate cancer, preoperative hypertriglyceridemia was linked to a lower risk of biochemical recurrence after radical prostatectomy [12]. Cholesterol is an essential structural and functional component of the cell membrane, and active lipogenesis with intracellular cholesterol accumulation is a hallmark of rapidly proliferating cancer cells [38]. Similar to other solid tumors, dysregulated cholesterol homeostasis is frequently observed in both precancerous lesions and malignant prostate tissue [39]. Because malignant cells undergo accelerated growth and proliferation, their metabolic turnover is increased, resulting in a higher demand for cholesterol to sustain membrane biosynthesis [40, 41]. This heightened utilization may contribute to lower peripheral serum cholesterol levels. In this context, the observed association between lipid metabolism–related toxicity and longer survival outcomes in our study may indicate that rezvilutamide plus ADT effectively suppresses tumor proliferation, thereby reducing cholesterol consumption by cancer cells. This reduced utilization could lead to higher circulating cholesterol levels, which manifest clinically as lipid abnormalities. Importantly, this observed association is hypothesis-generating and may reflect more effective drug exposure or underlying host factors rather than a direct causal effect.
This study also demonstrated that patients who developed grade ≥3 lipid metabolism–related toxicity, including weight gain and hypertriglyceridemia, experienced greater improvements in QoL scores compared with those without grade ≥3 events. Weight gain may reflect improved appetite and nutritional status, which in turn could enhance overall well-being. Moreover, the occurrence of lipid metabolism–related toxicity might suggest more active drug metabolism, potentially contributing to better tumor control, relief of cancer-related symptoms, and consequently improved QoL [18]. Importantly, several studies have shown that physical exercise and nutritional interventions can improve both metabolic health and QoL in patients with prostate cancer [42–44]. Therefore, the greater improvements in QoL scores observed in patients with grade ≥3 lipid metabolism–related toxicity in this study may also be partly explained by the adoption of appropriate exercise and dietary interventions following the onset of lipid metabolism–related abnormalities. Importantly, the occurrence of lipid metabolism–related toxicity should be interpreted as a surrogate marker of drug metabolism or lifestyle modifications rather than as a direct beneficial effect of the toxicity itself.
Elevations in liver function parameters such as AST, ALT, and ALP are commonly reported adverse events with second-generation AR inhibitors [23, 24]. In the CHART study, 24.6% of patients treated with rezvilutamide plus ADT experienced any-grade hepatotoxicity, most frequently elevated AST (20.1%) and ALT (19.2%), followed by GGT (6.2%), abnormal liver function (0.9%), and increased bilirubin (1.2%). To date, few studies have systematically examined the association between hepatotoxicity and survival or QoL outcomes in prostate cancer. In this post hoc analysis, hepatotoxicity did not significantly influence either survival or QoL in patients with mHSPC. Rezvilutamide is primarily metabolized via oxidative decarboxylation, with cytochrome P450 enzymes playing only a minor role; pharmacokinetic studies have also shown that liver function parameters do not meaningfully affect its clearance [18, 45]. These metabolic characteristics may partly explain the absence of a link between hepatotoxicity and adverse outcomes in this study. Nevertheless, the possibility of bias due to the relatively small number of patients with hepatotoxicity in CHART (79 patients, 24.6%) and limited statistical power cannot be excluded.
Although this study is the first to explore the potential impact of hepatotoxicity and lipid metabolism–related toxicity on survival and QoL, several limitations should be acknowledged. First, as a post hoc analysis not prespecified in the original study protocol, the findings may be influenced by unmeasured or uncontrolled confounders, including age, performance status, comorbidities, and concomitant medications. Second, the limited sample sizes for specific lipid metabolism–related toxicities precluded separate analyses of hypertriglyceridemia, hypercholesterolemia, or weight gain on survival and QoL outcomes, restricting mechanistic interpretation. Finally, data on overall nutritional status, dietary patterns, physical activity, and use of interventions to manage lipid metabolism–related toxicity were not collected, though these factors may influence prognosis and QoL in patients with prostate cancer. Future prospective studies with larger cohorts and systematic monitoring of lipid metabolism–related parameters are warranted to further elucidate their associations with survival outcomes and QoL.
Conclusions
To our knowledge, this is the first study to evaluate the impact of hepatotoxicity and lipid metabolism–related toxicity on survival outcomes and QoL in patients with high-volume mHSPC treated with rezvilutamide plus ADT. The findings indicate that hepatotoxicity was not significantly associated with survival or QoL outcomes. In contrast, patients who developed lipid metabolism–related toxicity experienced longer PFS and OS, and those with grade ≥3 lipid metabolism–related toxicity demonstrated greater improvements in QoL scores from baseline. It should be emphasized that these associations likely reflect the interplay of multiple factors and do not imply a direct beneficial effect of the toxicity itself.
Acknowledgements
We thank all patients and their families and all members of the collaborative group in this trial.
Abbreviations
- ADT
androgen deprivation therapy
- ALT
alanine aminotransferase
- AR
androgen receptor
- AST
aspartate aminotransferase
- CI
confidence interval
- CT
computed tomography
- ECOG
Eastern Cooperative Oncology Group
- FACT-G
Functional Assessment of Cancer Therapy-General
- FACT-P
Functional Assessment of Cancer Therapy–Prostate
- GGT
γ-glutamyl transferase
- HRQoL
Health-related QoL
- HRs
Hazard ratios
- LMRT
lipid metabolism–related toxicity
- mHSPC
metastatic hormone-sensitive prostate cancer
- MRI
magnetic resonance imaging
- NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
- NR
not reached
- OS
overall survival
- PCWG3
Prostate Cancer Working Group 3
- QoL
QoL
- RECIST
Response Evaluation Criteria in Solid Tumors
- rPFS
radiographic progression-free survival
- SE
standard errors
- TOI
Trial Outcome Index
Authors’ contributions
DY, BD contributed to the conception and design of the work. JW, SJ, HL, PD, ZW1 (Zeng-Jun Wang), NX, TM, ZW2 (Zhi-Ping Wang), XG, GZ, XX, ZS, YY, CW, GS, AZ, DD contributed to the acquisition of data. XD, CL, XZ contributed to the analysis and interpretation of data. JW, TW, TH contributed to the drafting of the manuscript. LW, JL, WW, DY, BD contributed to the critical revision of the manuscript for important intellectual content. XZ, CL contributed to the statistical analysis. DY, BD contributed to the administrative, technical, material support, and supervision. All authors read and approved the final manuscript.
Funding
This work was supported by the Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Data Availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The protocol and all amendments were approved by the Fudan University Shanghai Cancer Center Institutional Review Board (approval number: 1802181-1) and the independent ethics committees of all participating institutions. Written informed consent was obtained from all patients before initiation of study treatment.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Ding-Wei Ye, Email: dwyeli@163.com.
Bo Dai, Email: bodai1978@126.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.