Mocht u de informatie op kanker-actueel waarderen dan wilt u misschien ons ondersteunen met een donatie. We zijn een ANBI organisatie. Ook kunt u korting krijgen bij verschillende bedrijven op voedingssupplementen.

12 augustus 2019: Bron: Journal of Clinical Oncology Published online July 29, 2019.

Wanneer blaaskanker of urineleiderkanker eenmaal is uitgezaaid zijn er nog weinig behandelingsmogelijkheden. Maar nu lijkt een gericht medicijn getest in een fase II studie toch weer hoop te geven. 

Uit een fase II studie met Enfortumab vedotin, een zogeheten gericht medicijn op het eiwit Nectin-4, een expressie die vaak voorkomt bij urineleiderkanker, reageerde 44 procent met een gedeeltelijke remissie waaronder 12 procent met een complete remissie. 

De fase II studie werd uitgevoerd bij 125 patienten met voorbehandelde urineleiderkanker die eerder al immuuntherapie met een anti-PD hadden gehad (80 procent van de deelnemers) en chemokuren maar desondanks progressie van hun ziekte vertoonden. 90 procent van de patienten hadden uitzaaiingen, waarvan 40 procent in de lever en de meeste patienten waren in principe onbehandelbaar verklaard. Alle deelnemende patienten waren positief getest voor de eiwitexpressie Nectin-4. 

Mediane follow-up was 10.2 maanden

Objectieve response was gezien bij 55 patienten (44%), met 15 complete remissies (12%). Een aanvullende 35 patienten (28%) had stabiele ziekte. Tumoren waren in aantal en grootte verminderd bij 92 van de 110 evalueerbare patienten (84%). Response cijfers waren respectievelijk 56% en 41% bij patienten met en zonder reactie op immuuntherapie met anti–PD-1/L1 behandeling; 38% bij patienten met leveruitzaaiingen; en 41% bij patienten die al drie of meer chemokuren hadden gehad.  

Het volledige studierapport: Enfortumab Vedotin in Platinum- and Anti–PD-1/L1–Pretreated Urothelial Carcinoma is gratis in te zien.

Hier het abstract van de studie: 

Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy

Locally advanced or metastatic urothelial carcinoma is an incurable disease with limited treatment options, especially for patients who were previously treated with platinum and anti–programmed death 1 or anti–programmed death ligand 1 (PD-1/L1) therapy. Enfortumab vedotin is an antibody–drug conjugate that targets Nectin-4, which is highly expressed in urothelial carcinoma.

EV-201 is a global, phase II, single-arm study of enfortumab vedotin 1.25 mg/kg (intravenously on days 1, 8, and 15 of every 28-day cycle) in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum chemotherapy and anti–PD-1/L1 therapy. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review. Key secondary end points were duration of response, progression-free survival, overall survival, safety, and tolerability.

Enfortumab vedotin was administered to 125 patients with metastatic urothelial carcinoma. Median follow-up was 10.2 months (range, 0.5 to 16.5 months). Confirmed objective response rate was 44% (95% CI, 35.1% to 53.2%), including 12% complete responses. Similar responses were observed in prespecified subgroups, such as those patients with liver metastases and those with no response to prior anti–PD-1/L1 therapy. Median duration of response was 7.6 months (range, 0.95 to 11.30+ months). The most common treatment-related adverse events were fatigue (50%), any peripheral neuropathy (50%), alopecia (49%), any rash (48%), decreased appetite (44%), and dysgeusia (40%). No single treatment-related adverse events grade 3 or greater occurred in 10% or more of patients.

Enfortumab vedotin demonstrated a clinically meaningful response rate with a manageable and tolerable safety profile in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum and anti–PD-1/L1 therapies.

ACKNOWLEDGMENT

Writing assistance was provided by Heather Brignull, PhD, and Candice L. Willmon, PhD, of Seattle Genetics.

1. National Cancer Institute: SEER Cancer Stat Facts: Bladder Cancer. Bethesda, MDNational Cancer Institute2019 Google Scholar
2. von der Maase HHansen SWRoberts JT, et al: Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: Results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 18:3068-30772000 LinkGoogle Scholar
3. De Santis MBellmunt JMead G, et al: Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 30:191-1992012 LinkGoogle Scholar
4. Bellmunt Jvon der Maase HMead GM, et al: Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. J Clin Oncol 30:1107-11132012 LinkGoogle Scholar
5. Bellmunt Jde Wit RVaughn DJ, et al: Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376:1015-10262017 CrossrefMedlineGoogle Scholar
6. Powles TDurán Ivan der Heijden MS, et al: Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomised controlled trial. Lancet 391:748-7572018 CrossrefMedlineGoogle Scholar
7. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Bladder cancer (version .2.2019). https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf Google Scholar
8. Challita-Eid PMSatpayev DYang P, et al: Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 76:3003-30132016 CrossrefGoogle Scholar
9. Doronina SOToki BETorgov MY, et al: Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 21:778-7842003 [Erratum: Nat Biotechnol 21:941, 2003] CrossrefMedlineGoogle Scholar
10. Mandai KRikitake YMori M, et al: Nectins and nectin-like molecules in development and disease. Curr Top Dev Biol 112:197-2312015 CrossrefGoogle Scholar
11. Takai YIkeda WOgita H, et al: The immunoglobulin-like cell adhesion molecule nectin and its associated protein afadin. Annu Rev Cell Dev Biol 24:309-3422008 CrossrefGoogle Scholar
12. Takai YMiyoshi JIkeda W, et al: Nectins and nectin-like molecules: Roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol 9:603-6152008CrossrefGoogle Scholar
13. Zhang YZhang JShen Q, et al: High expression of nectin-4 is associated with unfavorable prognosis in gastric cancer. Oncol Lett 15:8789-87952018 Google Scholar
14. Lattanzio RGhasemi RBrancati F, et al: Membranous nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer. Oncogenesis 3:e1182014CrossrefGoogle Scholar
15. Takano AIshikawa NNishino R, et al: Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res 69:6694-67032009 CrossrefGoogle Scholar
16. Pavlova NNPallasch CElia AE, et al: A role for PVRL4-driven cell-cell interactions in tumorigenesis. eLife 2:e003582013 CrossrefGoogle Scholar
17. Rosenberg JESridhar SSZhang J, et al: Mature results from EV-101: A phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC). J Clin Oncol 37, 2019 (abstr 377LinkGoogle Scholar
18. Rosenberg JEHeath EPerez R, et al: Interim analysis of a phase I dose escalation trial of ASG-22CE (ASG-22ME; enfortumab vedotin), an antibody drug conjugate (ADC), in patients (Pts) with metastatic urothelial cancer (mUC). Ann Oncol 27, 2016 (abstr 788PCrossrefGoogle Scholar
19. 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
20. Vaughn DJBroome CMHussain M, et al: Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol 20:937-9402002 LinkGoogle Scholar
21. Bellmunt JChoueiri TKFougeray R, et al: Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens. J Clin Oncol 28:1850-18552010 LinkGoogle Scholar
22. Clopper CJPearson ESThe use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26:404-4131934 CrossrefGoogle Scholar
23. Drakaki AKirby CJVan der Heijden MS, et al: Docetaxel with or without ramucirumab after immune checkpoint inhibition in platinum-refractory metastatic urothelial carcinoma (mUC): Prespecified subgroup analysis from the phase 3 RANGE trial. J Clin Oncol 36, 2018(abstr 434LinkGoogle Scholar
24. Masters JCNickens DJXuan D, et al: Clinical toxicity of antibody drug conjugates: A meta-analysis of payloads. Invest New Drugs 36:121-1352018 CrossrefMedlineGoogle Scholar

Plaats een reactie ...

Reageer op "enfortumab vedotin geeft alsnog zeer goede resultaten met complete en gedeeltelijke remissies (44 procent) voor patienten met uitgezaaide urineleiderkanker waar immuuntherapie met anti-PD en chemokuren faalden"


Gerelateerde artikelen
 

Gerelateerde artikelen

Studiepublicaties van niet-toxische >> Balversa - erdafitinib, een >> bevacizumab toegevoegd aan >> Biomarker ERCC1 voorspelt >> Bestraling - radiotherapie >> Brachytherapie - inwendige >> Chemotherapie vooraf aan operatie >> Doorbraak na 30 jaar bij behandelen >> enfortumab vedotin geeft alsnog >> EOquin - E09 lijkt veelbelovend >>