Zie ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij borstkanker van arts-bioloog drs. Engelbert Valstar

Zie ook dit artikel: https://kanker-actueel.nl/sacituzumab-govitecan-trodelvy-een-anti-lichaam-medicijn-geeft-zeer-goede-resultaten-bij-borstkankerpatienten-met-voorbehandelde-uitgezaaide-triple-negatieve-borstkanker-met-trop-2-mutatie-in-vergelijking-met-chemotherapie.html

17 september 2022: Bron: ESMO 2022

Voor zwaar voorbehandelde gevorderde borstkankerpatienten  met HR positief en HER2 negatief geeft Sacituzumab govitecan (merknaam Trodelvy) dat bij triple negatieve borstkanker ook al goede resultaten liet zien (zie dit artikel) , nu ook uitstekende resultaten in vergelijking met een behandeling met chemotherapie naar keuze van de behandelende oncoloog. Sacituzumab govitecan  werkt op een zogeheten TROP-2 expressie. Nadeel van dit medicijn is dat het  ook wel behoorlijk wat bijwerkingen geeft ondanks dat de onderzoekers zeggen dat het veiligheidsprofiel van SG beheersbaar was, waarbij neutropenie en diarree de meest voorkomende behandelingsgerelateerde bijwerkingen waren. Zie omschrijving bij EMO. 

Deze resultaten komen uit de publicatie van de fase III studie bij totaal 543 borstkankerpatiënten (272 vs 271) en gepubliceerd in Journal of Clinical Oncology. 



Uit het abstract vertaald:

RESULTATEN

  • Patiënten werden willekeurig toegewezen aan SG (n = 272) of chemotherapie (n = 271). De mediane leeftijd was 56 jaar, 95% had viscerale metastasen en 99% had een eerdere cycline-afhankelijke kinase 4/6-remmer, met drie mediane chemotherapielijnen voor gevorderde ziekte ondergaan.
  • Het primaire eindpunt werd bereikt met een vermindering van 34% van het risico op progressie of overlijden (hazard ratio, 0,66 [95% BI, 0,53 tot 0,83; P = .0003]).
  • De mediane PFS was 5,5 maanden (95% BI, 4,2 tot 7,0) met SG en 4,0 maanden (95% BI, 3,1 tot 4,4) met chemotherapie;
  • De PFS na 6 en 12 maanden was 46% (95% BI, 39 tot 53) vs 30% (95% BI, 24 tot 37) en 21% (95% BI, 15 tot 28) vs 7% (95% BI , 3 tot 14), respectievelijk.
  • De mediane totale overleving (eerste geplande tussentijdse analyse) was nog niet bereikt (hazard ratio 0,84; P = 0,14). Belangrijkste graad 3 behandelingsgerelateerde bijwerkingen (SG versus chemotherapie) waren neutropenie (51% versus 38%) en diarree (9% versus 1%).

CONCLUSIE

Sacituzumab govitecan (merknaam Trodelvy) toonde statistisch significant langere ziekteprogressievrije tijd (PFS) ten opzichte van chemotherapie, met een beheersbaar veiligheidsprofiel bij patiënten met zwaar voorbehandelde, endocrien-resistente HR+/HER2-gevorderde borstkanker en beperkte behandelingsopties.

Er lopen nog twee andere studies met aanvullende fase III studies ter evaluatie van Sacituzumab govitecan bij HR+-borstkanker, waaronder GBG102-SASCIA (ClinicalTrials.gov identifier: NCT04595565)33 en EVER-132-002 (ClinicalTrials.gov identifier: NCT04639986).

Het volledige studierapport is gratis in te zien. Klik op de titel van het abstract.

 , MD1 , MD, MPH2 , MD, PhD3 , MD, PhD4,5 , MD, PhD6, MD, PhD7...Show More

*H.S.R. and A.B. contributed equally to this work.

Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Hormone receptor–positive (HR+) human epidermal growth factor receptor 2–negative (HER2–) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.

In this global, randomized, phase III study, SG was compared with physician's choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2– locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review.

Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade ≥ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%).

SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2– advanced breast cancer and limited treatment options.


ACKNOWLEDGMENT

We thank the patients and their caregivers for helping us realize the possibilities of this research. Thanks to the dedicated clinical trial investigators and their devoted team members who participated in this trial. The study was sponsored by Gilead Sciences Inc and was designed through a collaboration of the sponsor and the lead investigators. The authors would also like to thank Jin You, PharmD, and Dustin Chernick, PhD, of Gilead Sciences for their editorial assistance in preparation of this manuscript. Medical writing and editorial assistance were provided by Shala Thomas, PhD, CMPP, at Team 9 Science. The TROPiCS-02 Study Principal Investigators are listed in Appendix 1 (online only).

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