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

19 januari 2024: bron: npj Breast Cancer volume 9, Article number: 94 (2023)

De uiteindelijke eindanalyse van de Patricia studie bevestigt de goede resultaten die eerder werden gemeld voor 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 en waarbij de dosis herceptin (trastuzumab) wordt verhoogd en gegeven samen met pertuzumab.

Het bevestigde objectieve responspercentage van het CZS (het primaire eindpunt) was 11%. Het klinische voordeelpercentage in het CZS was 51% na 6 maanden. De mediane progressievrije overleving en totale overleving van het CZS waren respectievelijk 4,6 en 27,2 maanden. Er zijn geen nieuwe veiligheidssignalen geïdentificeerd.

Dit is de publicatie van de definitieve resultaten: 

Pertuzumab plus high-dose trastuzumab for HER2-positive breast cancer with brain metastases: PATRICIA final efficacy data

Abstract staat hieronder in dit artikel:

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.

1. Brufsky AMMayer MRugo HS, et al: Central nervous system metastases in patients with HER2-positive metastatic breast cancer: Incidence, treatment, and survival in patients from registHER. Clin Cancer Res 17:4834-48432011 CrossrefMedlineGoogle Scholar
2. Pestalozzi BCHolmes Ede Azambuja E, et al: CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: A retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol 14:244-2482013 CrossrefMedlineGoogle Scholar
3. Olson EMNajita JSSohl J, et al: Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast 22:525-5312013 CrossrefMedlineGoogle Scholar
4. Trastuzumab (HERCEPTIN) Prescribing Information. South San Francisco, CAGenentech2018 Google Scholar
5. Dijkers ECOude Munnink THKosterink JG, et al: Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther 87:586-5922010 CrossrefMedlineGoogle Scholar
6. Stemmler HJSchmitt MWillems A, et al: Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs 18:23-282007 CrossrefMedlineGoogle Scholar
7. Dawood SBroglio KEsteva FJ, et al: Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol 19:1242-12482008 CrossrefMedlineGoogle Scholar
8. Pertuzumab (PERJETA) Prescribing Information. South San Francisco, CAGenentech2020 Google Scholar
9. Swain SMBaselga JMiles D, et al: Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: Results from the randomized phase III study CLEOPATRA. Ann Oncol 25:1116-11212014 CrossrefMedlineGoogle Scholar
10. Bendell JCDomchek SMBurstein HJ, et al: Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972-29772003 CrossrefMedlineGoogle Scholar
11. Morikawa Ade Stanchina EPentsova E, et al: Phase I study of intermittent high-dose lapatinib alternating with capecitabine for HER2-positive breast cancer patients with central nervous system metastases. Clin Cancer Res 25:3784-37922019 CrossrefMedlineGoogle Scholar
12. Metzger OLeone JPLi T, et al: Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases. Ann Oncol 31:1231-12392020 CrossrefMedlineGoogle Scholar
13. Lewis Phillips GDNishimura MCLacap JA, et al: Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis. Breast Cancer Res Treat 164:581-5912017 CrossrefMedlineGoogle Scholar
14. Vogel CLCobleigh MATripathy D, et al: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719-7262002 LinkGoogle Scholar
15. Leyland-Jones BColomer RTrudeau ME, et al: Intensive loading dose of trastuzumab achieves higher-than-steady-state serum concentrations and is well tolerated. J Clin Oncol 28:960-9662010 LinkGoogle Scholar
16. Lin NULee EQAoyama H, et al: Response Assessment in Neuro-Oncology (RANO) group: Response assessment criteria for brain metastases: Proposal from the RANO group. Lancet Oncol 16:e270-e2782015 CrossrefMedlineGoogle Scholar
17. Eisenhauer EATherasse PBogaerts J, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-2472009 CrossrefMedlineGoogle Scholar
18. Bart JGroen HJHendrikse NH, et al: The blood-brain barrier and oncology: New insights into function and modulation. Cancer Treat Rev 26:449-4622000 CrossrefMedlineGoogle Scholar
19. Régina ADemeule MLaplante A, et al: Multidrug resistance in brain tumors: Roles of the blood-brain barrier. Cancer Metastasis Rev 20:13-252001 CrossrefMedlineGoogle Scholar
20. Fabi AAlesini DValle E, et al: T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer. Breast 41:137-1432018 CrossrefMedlineGoogle Scholar
21. Montemurro FDelaloge SBarrios CH, et al: Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: Exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial. Ann Oncol 31:1350-13582020 CrossrefMedlineGoogle Scholar
22. Kirschbrown WPWang BNijem I, et al: Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer. Cancer Chemother Pharmacol 84:539-5502019 CrossrefMedlineGoogle Scholar
23. Garg AQuartino ALi J, et al: Population pharmacokinetic and covariate analysis of pertuzumab, a HER2-targeted monoclonal antibody, and evaluation of a fixed, non-weight-based dose in patients with a variety of solid tumors. Cancer Chemother Pharmacol 74:819-8292014 CrossrefMedlineGoogle Scholar
24. Lin NUCarey LALiu MC, et al: Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 26:1993-19992008 LinkGoogle Scholar
25. Lin NUDiéras VPaul D, et al: Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 15:1452-14592009 CrossrefMedlineGoogle Scholar
26. Freedman RAGelman RSWefel JS, et al: Translational Breast Cancer Research Consortium (TBCRC) 022: A phase II trial of neratinib for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol 34:945-9522016 LinkGoogle Scholar
27. Saura COliveira MFeng Y, et al: Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. J Clin Oncol 37, 2019 (suppl 15; abstr 1005) LinkGoogle Scholar
28. Lin NUMurthy RAnders C, et al: Tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). J Clin Oncol 38, 2020 (suppl 15; abstr 1005) LinkGoogle Scholar
29. Bachelot TRomieu GCampone M, et al: Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): A single-group phase 2 study. Lancet Oncol 14:64-712013 CrossrefMedlineGoogle Scholar
30. Freedman RAGelman RSAnders CK, et al: Translational Breast Cancer Research Consortium: TBCRC 022: A phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol 37:1081-10892019 LinkGoogle Scholar

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