Rak-Prostaty ~ Prostate-Cancer

Hmmm, nowość w pigułce?

https://youtu.be/DkGi_04RLZM



Dodane przez -zb:

Orgovyx: New FDA Approved Hormone Therapy | 2020: The Year In Review | Mark Scholz, MD

Prostate Cancer Research Institute

Orgovyx (relugolix) is the latest frist-generation hormone therapy to be FDA approved for the treatment of advanced prostate cancer.
It comes in pill form and is thus more convenient than similar drugs like Lupron.
Early data also suggests that Orgovyx may be safer than the alternatives in patients with heart problems.

Orgovyx może się przydać do łatwego i szybkiego obniżenia testosteronu.

Zastanawiałem się w jaki sposób można przerwać monoterapię antandrogenową. Odstawienie bikalutamidu nie redukuje radykalnie poziomu testosteronu.
Orgovyx można by wtedy zastosować doraźnie.

FDA approves relugolix for advanced prostate cancer


On December 18, 2020, the Food and Drug Administration approved the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist, relugolix, (ORGOVYX, Myovant Sciences, Inc.) for adult patients with advanced prostate cancer.

Efficacy was evaluated in HERO (NCT03085095), a randomized, open label trial in men requiring at least one year of androgen deprivation therapy with either
prostate cancer recurrence following radiation or surgery or newly diagnosed castration-sensitive advanced prostate cancer.
Patients (N=934) were randomized (2:1) to receive relugolix 360 mg oral loading dose on the first day, followed by daily oral doses of 120 mg, or leuprolide acetate 22.5 mg injection subcutaneously every 3 months for 48 weeks.

The main efficacy outcome measure was medical castration rate defined as achieving and maintaining serum testosterone suppression to castrate levels (< 50 ng/dL) by day 29 through 48 weeks of treatment. The medical castration rate was 96.7% (95% CI: 94.9%, 97.9%) in the relugolix arm.

The most common adverse reactions (≥10%) in patients receiving relugolix in HERO were hot flush, musculoskeletal pain, fatigue, diarrhea, and constipation.
The most common laboratory abnormalities (≥15%) were increased glucose, triglycerides, alanine aminotransferase, and aspartate aminotransferase.
Decreased hemoglobin was also observed.

The recommended relugolix dose is a loading dose of 360 mg on the first day followed by a daily oral dose of 120 mg at approximately the same time with or without food.

https://www.fda.gov/drugs/drug-approval ... ate-cancer







A teraz o przewidywanym koszcie zastąpienia implantu z leuproreliną, np. Eligardu, przez doustną leuprorelinę czyli Relugolix (nazwa firmowa - Orgovyx.

Wg producenta leku, firmy Myovant, Orgovyx powinien pojawić się na rynku w styczniu 2021.
Cena hurtowa leku w USA będzie wynosiła USD $2,313 za opakowanie zawierające 30 120 mg tabletek, czyli miesiąc leczenia po pierwszej, potrójnej dozie leku (360 mg loading dose).


Holenderska apteka online, The Social Medwork, przewiduje, że koszt miesięcznego opakowania dla indywidualnego pacjenta będzie wynosił €4,394.00
https://thesocialmedwork.com/orgovyx-relugolix

W ramach badania klinicznego
HERO: A Multinational Phase 3 Randomized, Open-label, Parallel Group Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer NCT03085095 https://www.clinicaltrials.gov/ct2/show/NCT03085095

przeprowadzono dodatkowy nabór 101 mężczyzn z zaawansowanym CaP aby dokonać oceny czasu przeżycia do momentu, w którym CaP staje się odporny na kastrację podczas 48 tygodni leczenia relugolixem (leuprorelina w tabletkach) lub standardową formą leuproreliny (implant).

Konkluzja: Brak wyższości relugolixu nad standardową leuproreliną jeśli chodzi o czas przeżycia do momentu osiągnięcia odporności na kastrację u mężczyzn z przerzutowym rakiem prostaty






AUA 2021: Castration Resistance – Free Survival With Relugolix Is No Longer Than Leuprolide in Metastatic Prostate Cancer
An analysis of castration resistance – free survival in the HERO trial was conducted.

Practice Update Editorial Team

September 10, 2021—Las Vegas, Nevada

Castration resistance – free survival after 48 weeks of treatment of relugolix was no longer than with standard-of-care leuprolide in men with metastatic prostate cancer.
This outcome of an analysis of castration resistance – free survival in the multinational phase 3, randomized, open-label, parallel group HERO study was reported at AUA 2021, the 116th Annual Meeting of the American Urological Association, from September 10 – 13.

In HERO, Neal Shore, MD, of the Carolina Urologic Research Center, GenesisCare/Atlantic Urology Clinics, Myrtle Beach, South Carolina, and colleagues set out to evaluate the safety and efficacy of relugolix in men with advanced prostate cancer. Men were randomized 2:1 to relugolix 120 mg orally once daily after a single loading dose of 360 mg or leuprolide 3-monthly injections for 48 weeks.

To further characterize the efficacy profile of relugolix, the HERO study randomized an additional 101 men to assess a secondary endpoint of castration resistance - free survival during 48 weeks of treatment.
Castration resistance - free survival is a clinically relevant indicator of disease progression in the final analysis.
Castration resistance - free survival was defined as the duration from the date of the first dose to the date of confirmed PSA progression (defined by Prostate Cancer Clinical Trials Working Group 3) while castrated or death due to any reason, whichever occurs earlier.

Analysis of the HERO trial was conducted in the cohort with metastatic disease as well as in the overall modified intention-to-treat population.
Overall, 1074 men with advanced prostate cancer (n=717 relugolix, n=357 leuprolide) and 434 men with metastatic disease (n=290 relugolix, n=144 leuprolide) were included in the analysis of castration resistance - free survival (modified intent-to-treat population). Mean age of men with metastatic disease was 71 years, 29% of whom were older than 75 years of age. Men included in the analysis were from North and South America (28.9% and 6.4%), Europe (37.8%), and Asia/rest of world (26.9%).

At study entry, the most common location of metastasis was bone only (53%). Rates of castration resistance - free survival at week 48 in the cohort with metastatic disease were 74.3% (95% confidence interval 68.6%, 79.2%) and 75.3% (95% confidence interval 66.7%, 81.9%) in the relugolix and leuprolide groups, respectively (hazard ratio1.03 [0.68, 1.57], difference not significan). Results were similar in the overall modified intent-to-treat population. No new safety findings were identified.

Dr. Shore explained that androgen deprivation therapy is foundational treatment for achieving castration levels in men with advanced prostate cancer.
Relugolix is an FDA-approved, oral gonadotropin-releasing hormone receptor antagonist. The agent demonstrated suppression of testosterone to castrate levels in 96.7% of men, superior to leuprolide (88.8%), and 54% risk reduction in major adverse cardiovascular events relative to leuprolide in the phase 3 HERO study.

Dr. Shore concluded that in the HERO study, castration resistance - free survival assessed during 48 weeks of treatment with relugolix was not significantly longer than that with standard-of-care leuprolide in the subgroup of men with metastatic disease or in the overall modified intent-to-treat population.

https://www.practiceupdate.com/c/124132 ... d=20845155

Wiadomość z ostatniej chwili, zaprzyjaźniona apteka donosi że:

ORGOVYX pojawił się w hurtowniach,

Cena opakowania 120 mg 30 tabletek - 448,86 zł (rewelacyjnie tanio),

Lek jest także dostępny w opcji refundowanej. We wskazaniach refundacyjnych nie widać ograniczeń. Ciekawe czy lekarze będą skłonni do wypisywania darmowych recept?

Witaj Leonardo.

Dokonane przez Ciebie ustalenia dotyczące Orgoyxu brzmią bardzo interesująco i mogą mieć istotne znaczenie dla pacjentów, którzy z różnych względów woleliby uniknąć wstrzykiwania kolejnych implantów.

Jaka będzie praktyka urologów w w tym względzie? Mam nadzieję, że pozytywna, przekonamy się o tym już w najbliższych miesiącach.

Życzę Ci wszystkiego najlepszego w Nowym Roku.
Pozdrawiam Cię - Plaster

Refundowany ORGOVYX jest już dostępny w aptekach, na razie w 10, patrz niżej:


Orgovyx, cena i dostępność w aptekach w Polsce | Gdzie po lek
https://www.gdziepolek.pl/produkty/1211 ... ane/apteki

Zacytowany poniżej artykuł podsumowuje wyniki badania klinicznego II fazy relugoliks vs degareliks w kontekście neoadjuwantowej i adjuwantowej RT.

Relugoliks był lepszy od degareliksu jeśli chodzi o osiągnięcie kastracyjnego poziomu testosteronu (< 20 ng/dl).
Osiągnięcie poziomu kastracyjnego, dla degareliksu - 3 dni, dla reugoliksu - 4 dni (mediana).
Relugoliks był zdecydowanie lepszy jeśli chodzi otestosterone recovery, - u przeszło połowy (52%) pacjentów stosujących Orgovyx, po 3 miesiącach od przerwania leczenia testosteron powrócił do poziomu wyjściowego (degareliks - 16%).



Relugolix: A new kid on the block among gonadotrophin-releasing hormone antagonist

Relugolix was also tested in the neoadjuvant and adjuvant setting in combination with external beam radiotherapy in patients with intermediate-risk prostate cancer eligible for 6 months of ADT. The main objective of the phase II trial performed by Dearnaley et al. [15] was to investigate whether relugolix produces rapid and durable testosterone castration. Secondary end-points included testosterone kinetics, PSA levels, prostate volume, quality of life, and safety profile as well.

Patients were randomised either to receive relugolix per os 320 mg on day 1 followed by 120 mg daily or degarelix injection formula monthly for a total period of 24 weeks.
Both drugs achieved excellent castration results but when lower testosterone castration levels were applied (<20 ng/dL) relugolix achieved that goal in 82% of patients while degarelix in 68%.
The median time to castration was 3 days in the degarelix arm and 4 days in the relugolix arm.
Effects on PSA levels and prostate volume were similar among the two groups.
Regarding testosterone recovery, 52% of patients who received relugolix presented normal testosterone levels 3 months after treatment discontinuation compared with 16% of patients who received degarelix. No difference was noted in adverse events with the most common being nausea in both groups.

https://www.ncbi.nlm.nih.gov/pmc/articl ... :text=Both



Poniżej tabela z podsumowaniem wyników badania klinicznego HERO - relugoliks vs leuprorelina, tutaj zdecydowanie zwycięża relugoliks.