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https://kanker-actueel.nl/NL/palpociclib-plus-fulvestrand-geeft-langere-overall-overleving-en-progressievrije-ziekte-dan-alleen-fulvesrtrand-bij-hormoonresistente-borstkanker.html

19 april 2018: Bron: Journal of Clinical Oncology

Abemaciclib, een zogeheten kinaseremmer zoals ook palpociclib is, gegeven naast fulvestrant geeft een verbeterde progressievrije ziekte en een verbeterde overall overleving bij die patiënten waarbij abemaciclib aansloeg in vergelijking met alleen fulvestrant plus placebo.
PFS was mediaan, 16,4 v 9,3 maanden, hazard ratio, 0,553, 95% CI, 0,449 tot 0,681; P <.001).

Abemaciclib plus fulvestrant waarbij de aanpak aansloeg gaf een overall overleving (ORR) van 48,1% (95% CI, 42,6% tot 53,6%) in vergelijking met 21,3% (95% CI, 15,1% tot 27,6%) in de controlegroep.

Wel waren er voor abemaciclib behoorlijk wat meer bijwerkingen. De meest voorkomende bijwerkingen in de abemaciclib versus placebogroep waren diarree (86,4% versus 24,7%), neutropenie (46,0% v 4,0%), misselijkheid (45,1% versus 22,9%) en vermoeidheid (39,9% versus 26,9%).

Dit alles blijkt uit de resultaten van de fase III MONARCH-2 studie bij totaal 669 deelnemende patiënten. Abemaciclib plus fulvestrant (n = 446) of placebo plus fulvestrant (n = 223)

Figure

Uit het volledige studierapport: MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2− Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy dat gratis is in te zien hier de grafieken van de resultaten. Abstract plus referentielijst staat onderaan artikel.

Progressieziektevrije grafiek: Fig 2. Kaplan-Meier plots of progression-free survival. (A) Investigator-assessed and (B) independent central review of intent-to-treat population. HR, hazard ratio.

Figure

Overall overlevingsgrafiek hieronder:

Fig 4. Tumor response. (A) Best percent change in tumor size for all evaluable patients. Dotted horizontal line (−30%) corresponds to the partial response criteria defined by RECIST version 1.1. The vertical line is a visual to locate approximately 50% of patients. (B) Percentage change in tumor size from baseline by cycle (at day 1 of each cycle).

Figure

Conclusie van de onderzoekers:

Abemaciclib met 150 mg tweemaal daags plus fulvestrant was effectief, waardoor PFS en ORR significant werden verbeterd en een aanvaardbaar veiligheidsprofiel werd aangetoond bij vrouwen met hormoonreceptorpositieve en humane epidermale groeifactor receptor 2-negatieve gevorderde borstkanker die ziekte progressie vertoonden tijdens de hormoontherapie.

Het volledige studierapport: MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2− Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy is gratis in te zien.

Abstract plus referentielijst:

Abemaciclib plus fulvestrant was an effective treatment for patients with HR+/HER2− ABC whose disease progressed while they were receiving ET.

DOI: 10.1200/JCO.2017.73.7585 Journal of Clinical Oncology 35, no. 25 (September 1 2017) 2875-2884.

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2− Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy

MONARCH 2 (ClinicalTrials.gov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC).

MONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease. Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label). The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safety.

Between August 2014 and December 2015, 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P < .001). In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, 15.1% to 27.6%) in the control arm. The most common adverse events in the abemaciclib versus placebo arms were diarrhea (86.4% v 24.7%), neutropenia (46.0% v 4.0%), nausea (45.1% v 22.9%), and fatigue (39.9% v 26.9%).

Abemaciclib at 150 mg twice daily plus fulvestrant was effective, significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET.

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