Raadpleeg ook de literatuurlijst niet-toxische ondersteuning van arts-bioloog drs. Engelbert Valstar bij borstkanker.

13 augustus 2021: zie ook dit artikel: https://kanker-actueel.nl/olaparib-een-parpremmer-gegeven-aan-borstkankerpatienten-met-brca-1-en-brca-2-na-operatie-en-chemotherapie-verbetert-ziektevrije-overleving-met-9-procent.html

Zie ook dit artikel:

https://kanker-actueel.nl/NL/pi3k-remmer-buparlisib-naast-fulvestrant-geeft-30-tot-50-procent-langere-ziekteprogressievrije-tijd-maar-wel-meer-bijwerkingen-bij-gevorderde-borstkanker.html

Zie ook in gerelateerde artikelen

6 mei 2023: Uit nieuwe gegevens van de OlympiAD en de EMBRACA studies blijkt dat Olaparib toch betere resultaten laat zien in vergelijking met beste keuze van een oncoloog. Uit de laatste follow-up:

Belangrijkste punten uit de studie: :

De mediane totale overleving (OS) was respectievelijk 19,3 en 17,1 maanden voor olaparib versus chemotherapie naar keuze van de arts.
In totaal ontving 8,8% van de patiënten ten minste 3 jaar studiebehandeling in de olaparib groep versus geen patiënten in de TPC groep.
In de eerste lijn was de mediane OS numeriek langer voor olaparib versus TPC (respectievelijk 22,6 versus 14,7 maanden).
In de eerste lijn was het OS-percentage na 3 jaar 40,8% voor olaparib versus 12,8% voor TPC.

Deze gegevens bevestigen eerdere bevindingen en suggereren een mogelijk OS-voordeel voor olaparib bij eerstelijns gemetastaseerde borstkanker. Zie verder abstract onderaaan artikel en verder hier in dit artikel:

26 augustus 2018: Bron: Bron ESMO open

Voor borstkankerpatiënten met een erfelijke vorm van kanker met BRCA-1 en BRCA-2 mutaties en HER-2 negatieve expressie zijn PARP remmers, zoals olaparib en rucaparib en niraparib enz., de aangewezen behandeling als er sprake is van een recidief en uitzaaiingen na eerste- en tweedelijns behandelingen.

Echter nu blijkt uit een meta analyse en reviewstudie van twee gerandomiseerde studies met totaal 733 patiënten, dat weliswaar de progressievrije ziekte met enkele maanden werd verlengd en de kwaliteit van leven wel wat beter was voor de PARP groep. (In de subgroep analyse gerelateerd aan de hormoon receptor status, single-agent PARPi was geassocieerd met verbeterde progressievrije ziekte (PFS) met alleen in de hormoonnegatieve receptorgroep een statistisch significant verschil. (HR 0.51 (95% CI 0.37 to 0.71, p<0.001)) (I²=31.5%, p=0.227; figure 3A en niet in de hormoon receptor positieve groep (HR 0.62 (95% CI 0.36 to 1.07, p=0.085)) (I²=72.2%, p=0.058; figure 3B.)

Maar de uiteindelijke overall overleving verschilde niet in vergelijking met chemotherapie. (In de OlympiAD en de EMBRACA studies, respectievelijk, mediane OS was 19.3 maanden en 22.3 maanden in de PARPi groepen versus 19.6 maanden en 19.5 maanden in de chemotherapie groep).

Dit is de kernboodschap van deze reviewstudie:

This meta-analysis of two randomized controlled trials including 733 patients was designed to assess the safety, activity, and efficacy of single-agent PARP inhibitors compared with monochemotherapy in patients with BRCA-mutated HER2-negative metastatic breast cancer. Significant improvements in progression-free survival and objective response rates were observed with single-agent PARP inhibitors compared with chemotherapy. Patients treated with PARP inhibitors also reported a significant delay in time to quality-of-life deterioration. PARP inhibitor use led to a significantly increased risk of headache and anemia, and a decreased risk of palmar–plantar erythrodysesthesia syndrome and neutropenia compared with monochemotherapy.
These findings demonstrate the tolerability and efficacy of single-agent PARP inhibitors in this patient population.

parp-inhibition-apoptosis Source: Onclive.com

Klik op de titel van de studie om het volledige studierapport in te zien dat gratis is met veel verduidelijkende grafieken:

Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: a systematic review and meta-analysis

Hier het abstract uit ESMO Open:

http://dx.doi.org/10.1136/esmoopen-2018-000361

Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: a systematic review and meta-analysis

Francesca Poggio1,2,
Marco Bruzzone3,
Marcello Ceppi3,
Benedetta Conte2,
Samuel Martel4,
Christian Maurer5,
Marco Tagliamento2,
Giulia Viglietti6,
Lucia Del Mastro7,
Evandro de Azambuja1,
Matteo Lambertini1,6

Abstract

Single-agent poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved as the first targeted therapy available for patients with BRCA-mutated HER2-negative metastatic breast cancer. This meta-analysis aimed to better evaluate activity, efficacy and safety of single-agent PARPi in this population. A systematic search of Medline, Embase and conference proceedings up to 31 January 2018 was conducted to identify randomised controlled trials (RCTs) investigating single-agent PARPi versus monochemotherapy in patients with BRCA-mutated HER2-negative metastatic breast cancer. Using the random-effect model, we calculated summary risk estimates (pooled HR and OR with 95% CI) for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), any grade and grade 3–4 adverse events (AEs), treatment discontinuation rate and time to deterioration in quality of life (QoL). Two RCTs (n=733) were included. As compared with monochemotherapy, single-agent PARPi significantly improved PFS (HR 0.56(95% CI 0.45 to 0.70)) and ORR (OR 4.15 (95% CI 2.82 to 6.10)), with no difference in OS (HR 0.82 (95% CI 0.64 to 1.05)). Single-agent PARPi significantly increased risk of anaemia and any grade headache, but reduced risk of neutropenia and any grade palmar-plantar erythrodysesthesia syndrome as compared with monochemotherapy. No significant differences in other AEs and treatment discontinuation rate were observed. Patients treated with PARPi experienced a significant delayed time to QoL deterioration (HR 0.40 (95% CI 0.29 to 0.54)). Single-agent PARPi showed to be an effective, well tolerated and useful treatment in maintaining QoL of patients with BRCA-mutated HER2-negative metastatic breast cancer.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Acknowledgments

ML thanks the European Society for Medical Oncology (ESMO) for support in the form of a Translational Research Fellowship at the Institut Jules Bordet (Brussels, Belgium).

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View Abstract

Footnotes

Contributors All the authors make substantial contributions to conception and design, and/or acquisition of data, and/or analysis and interpretation of data, giving final approval of the version to be submitted.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests LDM received personal fees from Novartis Pharma AG, Roche-Genentech, Ipsen, Astrazeneca, Takeda, Eli Lilly outside the submitted work. EdA received honoraria from Roche-Genentech, research grant from Roche-Genentech (to the institution) and travel grants from Roche-Genentech and GlaxoSmithKline outside the submitted work. ML served as a consultant for Teva outside the submitted work.
Patient consent Not required.
Provenance and peer review Not commissioned; internally peer reviewed.

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© European Society for Medical Oncology (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

In first-line, the 3-year OS rate was 40.8% for olaparib versus 12.8% for treatment of physician's choice (TPC).

ORIGINAL RESEARCH| VOLUME 184, P39-47, MAY 2023

OlympiAD extended follow-up for overall survival and safety: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer

Published:February 14, 2023DOI:https://doi.org/10.1016/j.ejca.2023.01.031

Highlights

•
Median overall survival (OS) was 19.3 and 17.1 months for olaparib versus chemotherapy treatment of physician's choice (TPC), respectively.
•
Overall, 8.8% of patients received at least 3 years of study treatment in the olaparib arm versus no patients in the TPC arm.
•
In first-line, median OS was numerically longer for olaparib versus TPC (22.6 versus 14.7 months, respectively).
•
In first-line, the 3-year OS rate was 40.8% for olaparib versus 12.8% for TPC.
•
These data confirm previous findings and suggest a possible OS benefit for olaparib in the first-line metastatic breast cancer setting.

Abstract

Background

In the Phase III OlympiAD study, olaparib significantly prolonged progression-free survival versus chemotherapy treatment of physician's choice (TPC) in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC). In the final pre-specified analysis (64% maturity), median overall survival (OS) was 19.3 months for olaparib and 17.1 months for TPC (P = 0.513). Post-hoc extended follow-up, 25.7 months longer than previously reported for OS, is reported.

Patients and methods

Patients with gBRCAm, human epidermal growth factor receptor 2-negative mBC, who had received ≤2 lines of chemotherapy for metastatic disease, were randomised 2:1 to olaparib (300 mg bid) or TPC. During extended follow-up, OS was analysed every 6 months using the stratified log-rank test (overall population) and Cox proportional hazards model (pre-specified subgroups).

Results

In the overall population (302 patients; 76.8% maturity), median OS was 19.3 months for olaparib and 17.1 months for TPC (hazard ratio 0.89, 95% confidence interval 0.67–1.18); median follow-up was 18.9 and 15.5 months, respectively. Three-year survival was 27.9% for olaparib versus 21.2% for TPC. With olaparib, 8.8% of patients received study treatment for ≥3 years versus none with TPC. In first-line mBC, median OS was longer for olaparib than TPC (22.6 versus 14.7 months; hazard ratio 0.55, 95% confidence interval 0.33–0.95) and 3-year survival was 40.8% for olaparib versus 12.8% for TPC. No new serious adverse events related to olaparib were observed.

Conclusions

OS was consistent with previous analyses from OlympiAD. These findings support the possibility of meaningful long-term survival benefit with olaparib, particularly in first-line mBC.

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