mHSPC
Dotaz
Zobrazit nápovědu
Purpose: The addition of androgen receptor pathway inhibitors (ARPIs) to androgen deprivation therapy (ADT), with or without docetaxel (Doc), is currently recommended for metastatic, hormone-sensitive prostate cancer (mHSPC). Recently, the ARANOTE trial evaluated the efficacy and safety of Darolutamide + ADT in this setting. We aimed to update a network meta-analysis (NMA) of these combination therapies. Methods: We conducted a systematic search for RCTs on systemic therapies for mHSPC using MEDLINE, Embase, and the Web of Science Core Collection in September 2024. An NMA utilizing random-effects models was performed to compare progression-free survival (PFS), overall survival (OS), and adverse event (AE) incidence (PROSPERO: CRD42024591458). Results: A total of 12 RCTs (n = 11,954) were included in our NMAs. Triplet therapies were associated with significant improvements in PFS compared to ARPI-based doublet therapies (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.59-0.93; p = 0.01), but the difference did not reach the conventional levels of statistical significance for OS (HR: 0.82; 95% CI: 0.67-1.01; p = 0.059). In a subset analysis, compared to ARPI-based doublet therapies, triplet therapies showed a significant improvement in PFS in patients with high-volume disease (HR: 0.64; 95% CI: 0.47-0.88; p < 0.01), whereas no significant improvement was observed in those with low-volume disease (HR: 0.86; 95% CI: 0.45-1.67; p = 0.7). No significant difference in grade ≥ 3 AEs was observed between triplet therapies and ARPI-based doublet therapies. The main limitations include patient heterogeneity and limited follow-up in some studies. Conclusions: Triplet therapies can improve the oncologic outcomes of patients with mHSPC compared to ARPI-based doublet therapies, without significantly increasing severe AEs. These findings warrant further confirmation in a head-to-head trial powered for overall survival.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
V naší kazuistice prezentujeme komplexní léčbu pacienta s metastatickým hormonálně senzitivním karcinomem prostaty (mHSPC), se vstupně symptomatickým viscerálním postižením plic. Pacient profituje z dvojkombinační terapie (androgen deprivační terapii + apalutamid) s dobrou kvalitou života.
In our case report we want to demonstrate a complex therapy of a patient with metastatic hormone-sensitive prostate cancer (mHSPC) with initially symptomatic visceral metastases of lungs. Patient profits from doublet combination (androgen deprivation therapy + apalutamid) with good quality of life.
- Klíčová slova
- apalutamid, degarelix, androgen deprivační terapie,
- MeSH
- hormon uvolňující gonadotropiny terapeutické užití MeSH
- kombinovaná farmakoterapie metody škodlivé účinky MeSH
- lidé MeSH
- mediastinum diagnostické zobrazování patologie MeSH
- metastázy nádorů farmakoterapie MeSH
- nádory mediastina diagnostické zobrazování sekundární MeSH
- nádory plic diagnostické zobrazování sekundární MeSH
- nádory prostaty * diagnóza farmakoterapie komplikace MeSH
- pleurální výpotek diagnostické zobrazování MeSH
- prostatický specifický antigen analýza MeSH
- senioři MeSH
- staging nádorů MeSH
- thiohydantoiny * aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Metastatický hormonálně senzitivní karcinom prostaty (mHSPC) je různorodé onemocnění vyžadující individuální léčebný přístup. Androgen-deprivační terapie (ADT) je základem terapie diseminovaného onemocnění s velmi dobrou iniciální odpovědí na léčbu u většiny pacientů, ale s limitovaným trváním odpovědi. Léčba ADT v kombinaci s ARTA (androgen receptor targeted agents – abirateron, apalutamid, enzalutamid) významně prodlužuje přežití bez progrese (PFS) i celkové přežití (OS), a stala se tak standardem v léčbě pacientů s mHSPC. Obdobného účinku dosahuje i kombinovaná léčba ADT s docetaxelem, tedy tzv. dublet. U části pacientů s agresivním onemocněním ale tato terapie není dostatečně účinná. Jednou z možností, jak zvýšit účinnost léčby, je kombinace ADT s ARTA a docetaxelem, tedy tzv. triplet. V článku se zaměříme na základní studie týkající se této problematiky a pokusíme se definovat pacienty, pro které je tato kombinovaná léčba výhodná.
Metastatic hormone-sensitive prostate cancer is a diverse disease requiring an individual treatment approach. Androgen deprivation therapy (ADT) is the mainstay of treatment for disseminated disease with a very good initial response to treatment in most patients, but with a limited duration of response. Combined treatment with ADT and ARTA (androgen receptor targeted agents – abiraterone, apalutamide, enzalutamide) significantly prolongs progression-free survival (PFS) and overall survival (OS) and has thus become the standard of treatment for patients with mHSPC. A similar effect is achieved by combined treatment with ADT and docetaxel, the so-called doublet therapy. However, this treatment is not effective enough for some patients with aggressive disease. One possibility to increase the effectiveness of treatment is the combination of ADT with ARTA and docetaxel, the socalled triplet therapy. In this article, we will focus on basic studies regarding this issue and try to define patients for whom this combined treatment is beneficial.
- Klíčová slova
- darolutamid,
- MeSH
- abirateron terapeutické užití MeSH
- antagonisté androgenů * terapeutické užití MeSH
- docetaxel terapeutické užití MeSH
- kombinovaná terapie * metody MeSH
- lidé MeSH
- metastázy nádorů farmakoterapie MeSH
- nádory prostaty * farmakoterapie MeSH
- pyrazoly terapeutické užití MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. METHODS: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. RESULTS: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. CONCLUSIONS: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.
- MeSH
- antagonisté androgenních receptorů terapeutické užití MeSH
- antagonisté androgenů * terapeutické užití MeSH
- docetaxel * terapeutické užití aplikace a dávkování MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie mortalita patologie MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- síťová metaanalýza * MeSH
- tumor burden MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
CONTEXT: It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression. OBJECTIVE: To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP). EVIDENCE ACQUISITION: Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT). EVIDENCE SYNTHESIS: Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract. CONCLUSIONS: In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting. PATIENT SUMMARY: Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.
- MeSH
- antagonisté androgenů terapeutické užití MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory prostaty * patologie terapie MeSH
- prostatektomie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
INTRODUCTION: Metastatic hormone-sensitive prostate cancer (mHSPC) displays both simultaneous and sequential patterns of metastasis, emphasizing a comprehensive treatment approach that integrates both local therapy and systemic treatment strategies. The increasing use of molecular imaging has led to a rise in mHSPC diagnoses, underscoring the importance of identifying the right patient population and effective treatment concepts for this disease state. RESULTS: Two prospective trials, HORRAD and STAMP EDE, investigated prostate radiotherapy (RT) for mHSPC; however, they did not show an overall survival (OS) benefit in the unselected cohort. Nonetheless, RT showed favorable outcomes in patients with fewer than five bone metastases, resulting in a 7% 3-year survival improvement and supporting the integration of RT in multimodal treatment for men with oligometastatic mHSPC. Regarding cytoreductive prostatectomy (cRP), the TRoMbone Trial confirmed its feasibility and safety. In addition, findings from the FUSCC-OMPCa Trial demonstrated improved 3-year radiographic progression-free survival and OS rates with acceptable rates of complications and incontinence. Recent data from the LoMP registry have further supported superior OS and cancer-specific survival (CSS) in patients undergoing cRP compared to systemic therapy alone. Notably, no significant differences in OS and CSS were observed between the cRP and RT groups. However, cRP-treated patients exhibited superior 2-year local event-free survival when compared to those treated with RT. CONCLUSION: RT in combination with systemic therapy remains the established first-line treatment for low-burden mHSPC, though the exact definition of low metastatic burden remains contentious. Precise assessment of metastatic burden is vital to identify patients who would derive the greatest benefit from RT. As treatment paradigms evolve, embracing multimodal approaches holds potential for optimizing outcomes in patients with mHSPC. Further research is needed to solidify the role of cRP as a standard therapeutic approach and to refine treatment strategies for improved patient outcomes.
- Publikační typ
- časopisecké články MeSH
Androgen-deprivační terapie (ADT) je základem léčby pokročilého a metastatického karcinomu prostaty. Zařazení léků cílených na androgenní receptor (ARTA) vedlo ke zlepšení výsledků terapie. Nejprve byly ARTA využívány v terapii metastatického kastračně rezistentního karcinomu prostaty (mCRPC) v „prechemo“ a „postchemo“ indikaci. Následně proběhly další klinické studie a ARTA se staly i součástí terapie metastatického hormonálně senzitivního karcinomu prostaty (mHSPC). V posledních letech bylo provedeno několik klinických studií, v nichž byly ARTA kombinovány s chemoterapií (sekvenčně nebo konkomitantně) a dalšími třídami léků (např. inhibitory PARP, ipatasertibem či imunoterapií).
Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced and metastatic prostate cancer. The inclusion of androgen receptor-targeted therapy (ARTA) has led to improved treatment outcomes. Initially, ARTAs were used in the treatment of metastatic castration -resistant prostate cancer (mCRPC) in „prechemo“ and „postchemo“ indications. Subsequently, further clinical trials were conducted and ARTAs became a part of the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, several clinical trials have been carried out in which ARTAs have been combined with chemotherapy (sequential or concomitant) and other classes of drugs (e.g. PARP inhibitors, ipatasertib or immunotherapy).
- Klíčová slova
- hormonálně senzitivní karcinom prostaty,
- MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie MeSH
- protinádorové látky MeSH
- protokoly protinádorové léčby MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Základem systémové léčby metastatického hormonálně senzitivního karcinomu prostaty (mHSPC) je androgen-deprivační terapie (ADT). Samotná ADT má časově omezený účinek, a to na dobu 2–3 let. V posledních letech proto proběhly klinické studie, které u vybraných pacientů prokázaly přínos kombinace ADT + chemoterapie, případně ADT + ARTA (léčba cílená na androgenní receptor). Další rozšíření léčebných možností spočívá v tripletové kombinaci ADT + chemoterapie + ARTA. Na podkladě výsledků klinických studií ARASENS a PEACE-1 se tento léčebný postup také stal součástí léčebných doporučení. Tento přehledový článek se zabývá možnostmi využití tripletu v léčbě mHSPC.
.The mainstay of systemic treatment of metastatic hormone-sensitive prostate cancer (mHSPC) is androgen deprivation therapy (ADT). ADT alone has a limited effect over a period of time, namely 2–3 years. Therefore, in recent years, clinical trials have been conducted that have demonstrated the benefit of a combination of ADT + chemotherapy or ADT + ARTA (androgen receptor targeted therapy) in selected patients. Further expansion of treatment options lies in the triplet combination of ADT + chemotherapy + ARTA. Based on the results of the ARASENS and PEACE-1 clinical trials, this treatment approach has also become part of the treatment recommendations. This review article discusses the potential use of triplets in the treatment of mHSPC.
BACKGROUND: Combination systemic therapies have become the standard for metastatic hormone-sensitive prostate cancer (mHSPC). However, the effect of age on oncologic outcomes remains unknown. Our aim was to perform a systematic review, meta-analysis, and network meta-analysis (NMA) on the effect of chronological age on overall survival (OS) in patients treated with combination therapies for mHSPC. METHODS: We searched the PubMed®, Web of ScienceTM, and Scopus® databases to identify randomized controlled trials (RCTs) that analyzed the efficacy of combination systemic therapies using ADT plus docetaxel and/or androgen receptor signaling inhibitor (ARSI) in patients with mHSPC. We included studies, which provided separate hazard ratios (HRs) for younger vs. older patients. The selected age cut-off was 70 years (±5 years). Our outcome of interest was OS. RESULTS: We included nine RCTs with a total of 9183 patients. Younger and older men constituted 51% and 49% of included patients, respectively. Docetaxel plus ADT significantly improved OS among both older (HR 0.79, 95% CI 0.63-0.99, p = 0.04) and younger patients (HR 0.79, 95% CI 0.69-0.90, p < 0.001) with no differences according to age. ARSI plus ADT improved OS in older (HR 0.72, 95% CI 0.64-0.80, p < 0.001) and younger (HR 0.58, 95% CI 0.51-0.66, p < 0.001) patients; younger patients did benefit more (p = 0.02). On NMA treatment ranking, triplet therapy showed the highest probability of OS benefit irrespective of age group; in older patients, the benefit of triplet therapy compared to doublet was less expressed. CONCLUSIONS: Patients with mHSPC benefit from combination systemic therapies irrespective of age; the effect is, however, more evident in younger patients. Chronological age alone seems not to be a selection criteria for the administration of combination systemic therapies.
- MeSH
- antagonisté androgenů terapeutické užití MeSH
- docetaxel MeSH
- hormony terapeutické užití MeSH
- lidé MeSH
- nádory prostaty * patologie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
