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

8 oktob er 2022: Aanvullend op onderstaande studie is deze studie gepubliceerd die aantoont dat een groot deel van de patiënten lage of geen HER-2 expressie hadden en waarbij Sacituzumab govitecan (merknaam Trodelvy) ook goede resultaten liet zien bij deze groep van patiënten met borstkanker:

Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study

Conclusie: In de intent-to-treat (ITT)-populatie en in elke behandelgroep was 92% van de patiënten HER2 IHC0 of HER2-Laag. De baselinekenmerken tussen HER2 IHC0 en HER2-Laag waren vergelijkbaar en vergelijkbaar met die van de ITT-populatie. De mediane PFS was verbeterd met SG versus TPC in de HER2 IHC0- en HER2-Laag-groepen (respectievelijk HR 0,72, P=0,05 en 0,58, P<0,001; tabel). Het veiligheidsprofiel van de subgroepen kwam overeen met dat van de totale veiligheidspopulatie.

Abstract staat onderaan artikel.

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.

Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

Hope S. Rugo , MD1; Aditya Bardia , MD, MPH2; Frederik Marmé , MD, PhD3; Javier Cortes , MD, PhD4,5; Peter Schmid , MD, PhD6; Delphine Loirat, 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/

ABSTRACT

PURPOSE

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.

METHODS

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.

RESULTS

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%).

CONCLUSION

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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Sacituzumab govitecan (SG) should be considered an effective treatment option for pts with HR+/HER2- MBC, regardless of HER2 status.

ABSTRACT ONLY| VOLUME 33, SUPPLEMENT 7, S635-S636, SEPTEMBER 01, 2022
214MO Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study

DOI:https://doi.org/10.1016/j.annonc.2022.07.253

214MO Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study


Background

Tumors with HER2 IHC1+ or IHC2+ combined with a negative in situ hybridization (ISH) test are described as HER2-Low. SG, a novel Trop-2–directed antibody-drug conjugate, is approved for patients (pts) with metastatic triple-negative breast cancer in the second-line or greater setting. In the TROPiCS-02 study, SG demonstrated a 34% reduction in risk of progression or death vs treatment of physician’s choice (TPC) in heavily pretreated, endocrine-resistant HR+/HER2– MBC (Rugo H, et al. ASCO 2022; LBA1001). In this TROPiCS-02 post hoc analysis, we describe SG efficacy in HER2 IHC0 and HER2-Low HR+/HER2– MBC.

Methods

Pts with HR+/HER2– unresectable locally advanced or MBC and 2-4 prior chemotherapy regimens for MBC were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS) per RECIST 1.1 by central review. Pts with known HER2-positive disease were ineligible, with HER2 status (IHC and ISH) assessed locally.
Table: 214MO
HER2 IHC0 SG (n=101) TPC (n=116)HER2-Low* SG (n=149) TPC (n=134)
mPFS, mo 5.0 3.4 6.4 4.2
HR (95% CI) 0.72 (0.51-1.00) P=0.05 0.58 (0.42-0.79) P<0.001
ORR, n (%) 16 (16) 17 (15) 38 (26) 16 (12)
ISH, in situ hybridization; IHC, immunohistochemistry; mPFS, median progression-free survival; ORR, objective response rate; pts, patients; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.
*39 of 117 IHC2+ pts (33%; 14% of all HER2-Low pts) did not have an ISH test result but were assumed to be ISH-negative due to study eligibility criteria (HER2− disease). Similar results were observed when the 39 pts were excluded from the analysis.

Results

In the intent-to-treat (ITT) population and in each treatment arm, 92% of pts were HER2 IHC0 or HER2-Low. Baseline characteristics between HER2 IHC0 and HER2-Low were comparable and similar to that of the ITT population. Median PFS was improved with SG vs TPC in the HER2 IHC0 and HER2-Low groups (HR 0.72, P=0.05 and 0.58, P<0.001, respectively; Table). The safety profile of the subgroups was consistent with that of the overall safety population.

Conclusions

Clinical benefit with SG vs TPC in HER2 IHC0 and HER2-Low HR+/HER2- MBC was consistent with that of the TROPiCS-02 ITT population. SG should be considered an effective treatment option for pts with HR+/HER2- MBC, regardless of HER2 status.

Article Info

Identification

DOI: https://doi.org/10.1016/j.annonc.2022.07.253

Copyright

© 2022 European Society for Medical Oncology. Published by Elsevier Inc. All rights reserved.

ScienceDirect

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Tables


Sacituzumab govitecan, borstkanker HR pos, HER2 neg., overall overleving, ziekte progressievrije tijd, ESMO 2022


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