28 augustus 2023: zie ook dit artikel: https://kanker-actueel.nl/pertuzumab-plus-trastuzumab-geeft-zelfde-2-jaars-overall-overleving-met-of-zonder-chemotherapie-bij-patienten-met-uitgezaaide-borstkanker-met-her2-positief.html

24 mei 2021: Bron: Journal of Clinical Oncology

Uit een kleinschalige studie (N = 39 patiënten) blijkt dat wanneer bij borstkankerpatiënten met HER2-positieve expressie en uitzaaiingen in de hersenen (Central Nervous System (CNS) en toch ziekteprogressie laten zien na te zijn bestraald op die CNS uitzaaiingen de dosis herceptin (trastuzumab) wordt verhoogd en gegeven samen met pertuzumab een aantal patiënten (68 procent van de deelnemers) stabiele ziekte bereikt die minimaal 4 maanden aanhoudt. 

Hoewel het een klein aantal deelnemers betreft zeggen de onderzoekers dat deze bevindingen wel degelijk van belang zijn voor met name patiënten in eerder stadium van hun ziekte.

Hier het belang van de studie volgens de onderzoekers:

  • Key Objective

  • Development of CNS metastasis is common in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC), but systemic therapies effective against brain metastases are limited. The phase II PATRICIA study examined pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) in patients with HER2-positive MBC with CNS metastases that had progressed following radiotherapy.

  • Knowledge Generated

  • Although the overall response rate in the CNS was limited, 68% of patients treated with pertuzumab plus high-dose trastuzumab experienced clinical benefit in the CNS. No new safety signals were observed.

  • Relevance

  • Despite prior assumptions that antibody treatments are unable to penetrate the CNS, we observed that pertuzumab plus high-dose trastuzumab may have clinical activity against progressive CNS metastases in some patients with HER2-positive MBC. Future studies should further investigate antibody-based regimens, including high-dose trastuzumab in combination with chemotherapy or other targeted therapies, to optimize the treatment of CNS disease.

Hier het studieprotocol van de studie: A Study of Pertuzumab With High-Dose Trastuzumab for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (MBC) With Central Nervous System (CNS) Progression Post-Radiotherapy

Lees het uitgebreide studieverslag dat gratis is in te zien en heel gedetailleerd wordt beschreven. Klik op de titel van het abstract voor het studierapport.

Effective therapies are needed for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) with brain metastases. A trastuzumab radioisotope has been shown to localize in brain metastases of patients with HER2-positive MBC, and intracranial xenograft models have demonstrated a dose-dependent response to trastuzumab.

In the phase II PATRICIA study (ClinicalTrials.gov identifier: NCT02536339), patients with HER2-positive MBC with CNS metastases and CNS progression despite prior radiotherapy received pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. The primary end point was confirmed objective response rate (ORR) in the CNS per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary end points included duration of response, clinical benefit rate (complete response plus partial response plus stable disease ≥ 4 or ≥ 6 months) in the CNS, and safety.

Thirty-nine patients were treated for a median (range) of 4.5 (0.3-37.3) months at clinical cutoff. Thirty-seven patients discontinued treatment, most commonly because of CNS progression (n = 27); two remained on treatment. CNS ORR was 11% (95% CI, 3 to 25), with four partial responses (median duration of response, 4.6 months). Clinical benefit rate at 4 months and 6 months was 68% and 51%, respectively. Two patients permanently discontinued study treatment because of adverse events (left ventricular dysfunction [treatment-related] and seizure, both grade 3). No grade 5 adverse events were reported. No new safety signals emerged with either agent.

Although the CNS ORR was modest, 68% of patients experienced clinical benefit, and two patients had ongoing stable intracranial and extracranial disease for > 2 years. High-dose trastuzumab for HER2-positive CNS metastases may warrant further study.

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