Comparison of doublet and triplet therapies for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis

Wang, Lei; Li, Chunxing; Zhao, Zichen; Li, Xiaojian; Tang, Chong; Guan, Zhi‐Zhong; Sun, Feng; Gu, Jin; Li, Ning-chen

doi:10.3389/fonc.2023.1104242

Cited by 7 publications

(3 citation statements)

References 49 publications

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“…11 Several clinical factors should be considered including burden of disease, visceral metastases (especially liver), performance status, and synchronous versus metachronous at presentation. [12][13][14] A majority of prostate cancer patients in Canada die having never received docetaxel despite its survival benefits, reflecting challenges of applying trial data to real world patients who are older with more comorbidities. A Canadian retrospective population-based study showed that only 11% of de novo mCSPC patients received ADT-docetaxel when it was the only available ADT-intensification option and only 44% completed ≥6 cycles of docetaxel.…”

Section: Discussionmentioning

confidence: 99%

Addressing controversial areas in the management of advanced prostate cancer in Canada

Saad,

Hotte,

Noonan

et al. 2023

CUAJ

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Introduction: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. Methods: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for “consensus agreement” set at 75%. Results: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and PARP inhibitors for BRCA-positive prostate cancer. Conclusions: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

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Section: Discussionmentioning

confidence: 99%

Addressing controversial areas in the management of advanced prostate cancer in Canada

Saad,

Hotte,

Noonan

et al. 2023

CUAJ

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“…Improvements in OS with ADT plus ARPI plus docetaxel vs ADT plus docetaxel have been confirmed in several meta-analyses, with indirect network meta-analyses suggesting that the triple regimen may also rank ahead of ADT plus ARPI . The efficacy benefit of ADT plus ARPI plus docetaxel over ADT plus ARPI needs to be confirmed in prospective head-to-head studies.…”

Section: Observationsmentioning

confidence: 99%

Metastatic Hormone-Sensitive Prostate Cancer and Combination Treatment Outcomes

Hussain,

Fizazi,

Shore

et al. 2024

JAMA Oncol

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ImportanceMetastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to castration-resistant disease, the terminal phase. This review provides a summary of the most recent evidence for current and emerging management strategies, including treatment intensification with combinations of therapies. It also provides recommendations on applying the evidence in clinical practice to encourage appropriate treatment to improve survival outcomes among patients with metastatic hormone-sensitive prostate cancer.ObservationsAndrogen-deprivation therapy is the backbone of treatment for metastatic hormone-sensitive prostate cancer; however, it is insufficient alone to provide sustained disease control and long-term survival. Addition of an androgen receptor pathway inhibitor and/or docetaxel significantly improves survival, as demonstrated by several international phase 3 randomized clinical trials. Triplet therapy composed of androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel has been shown to improve overall survival over androgen-deprivation therapy plus docetaxel. In the ARASENS trial (darolutamide), the hazard ratios (HRs) were 0.68 (95% CI, 0.57-0.80) in the overall population; 0.71 (95% CI, 0.59-0.85) and 0.61 (95% CI, 0.35-1.05) in patients with de novo and recurrent disease, respectively; 0.69 (95% CI, 0.57-0.82) and 0.72 (95% CI, 0.41-1.13) in patients with high-volume and low-volume disease, respectively; and 0.71 (95% CI, 0.58-0.86) and 0.62 (95% CI, 0.42-0.90) in patients with high-risk and low-risk disease, respectively. In the PEACE-1 trial (abiraterone acetate + prednisone), the HRs were 0.75 (95% CI, 0.59-0.95; all de novo) in the overall population and 0.72 (95% CI, 0.55-0.95) and immature in the high-volume and low-volume subgroups, respectively. In the ENZAMET trial (enzalutamide), the HRs were 0.82 (95% CI, 0.63-1.06) in the overall population; 0.73 (95% CI, 0.55-0.99) and 1.10 (95% CI, 0.65-1.86) in the de novo and recurrent subgroups, respectively; and 0.87 (95% CI, 0.66-1.17) and 0.61 (95% CI, 0.33-1.10) in the high-volume and low-volume subgroups. Combination regimens are generally well tolerated, with adverse effects dependent on the profiles of the component drugs.Conclusions and relevanceThe findings of this review show compelling evidence from phase 3 randomized clinical trials in favor of initiating triplet combination therapy for patients with metastatic hormone-sensitive prostate cancer for the best overall survival. Patients who are eligible for chemotherapy should be offered androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel, particularly patients with high-volume, high-risk, or de novo metastatic disease.

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“…The usage of ARTA is recommended in combination with androgen deprivation therapy (ADT) or in triplet combination with ADT and chemotherapy in mPCa. Although the triplet combination has shown superior efficacy compared to the doublet combination in high-volume prostate cancer, it is important to note that the incidence of adverse events is also higher [20]. The potential relationship between the molecular pathways of metformin and silodosin in the treatment of prostate cancer suggests that both drugs should be considered as viable adjunctive therapies in the management of mPCa.…”

Section: Introductionmentioning

confidence: 99%

Effects of metformin and silodosin as supplementary treatments to abiraterone on human telomerase reverse transcriptase (hTERT) level in metastatic castration-resistant prostate cancer (mCRPC) cells: An in vitro study

Hidayatulla,

Andhika,

Prasetyawan

et al. 2024

Narra J

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The antiproliferative properties of metformin and silodosin have been observed in prostate cancer. Furthermore, it is hypothesized that the molecular pathways related to these drugs may impact the levels of human telomerase reverse transcriptase (hTERT) in prostate cancer cells. The aim of this study was to assess the effect of metformin and silodosin on the levels of hTERT in metastatic castration-resistant prostate cancer (mCRPC) cells. The present study employed an experimental design with a post-test-only control group. This study utilized the PC3 cell line as a model for mCRPC. A viability experiment was conducted using the CCK-8 method to determine the inhibitory concentration (IC50) values of metformin, silodosin, and abiraterone acetate (AA) after a 72-hour incubation period of PC3 cells. In order to investigate the levels of hTERT, PC3 cells were divided into two control groups: a negative control and a standard therapy with AA. Additionally, three experimental combination groups were added: metformin with AA; silodosin with AA; and metformin, silodosin and AA. The level of hTERT was measured using sandwich ELISA technique. The difference in hTERT levels was assessed using ANOVA followed by a post hoc test. The IC50 values for metformin, silodosin, and AA were 17.7 mM, 44.162 mM, and 66.9 μM, respectively. Our data indicated that the combination of metformin with AA and the combination of metformin, silodosin and AA decreased the hTERT levels when compared to control, AA, and silodosin with AA. The administration of metformin resulted in a reduction of hTERT levels in the PC3 cell line, but the impact of silodosin on hTERT levels was not statistically significant compared to AA group.

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Comparison of doublet and triplet therapies for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis

Cited by 7 publications

References 49 publications

Addressing controversial areas in the management of advanced prostate cancer in Canada

Addressing controversial areas in the management of advanced prostate cancer in Canada

Metastatic Hormone-Sensitive Prostate Cancer and Combination Treatment Outcomes

Effects of metformin and silodosin as supplementary treatments to abiraterone on human telomerase reverse transcriptase (hTERT) level in metastatic castration-resistant prostate cancer (mCRPC) cells: An in vitro study

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