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

17 oktober 2021: Zie ook dit artikel: https://kanker-actueel.nl/pembrolizumab-eerstelijns-gegeven-plus-chemotherapie-bij-aanhoudende-of-recidief-of-uitgezaaide-baarmoederhalskanker-geeft-betere-ziektevrije-en-overall-overleving-plus-33-procent-dan-placebo.html

16 oktober 2021: Bron: 2021 May;22(5):609-619

De FDA heeft versnelde goedkeuring gegeven aan tisotumab vedotin-tftv (Tivdak, Seagen/Genmab), een antilichaam dat zich richt op een bepaalde receptor van tumorweefsel voor volwassenen met een recidief of progressie van uitgezaaide baarmoederhalskanker tijdens of na chemotherapie. De FDA gaf deze toestemming nadat de resultaten van een fase II studie werden bekendgemaakt. 

Tisotumab vedotin gaf bij totaal 102 patiénten die aan de studie meededen tot aan de analyse echt hoopvolle en duurzame antitumoractiviteit met een beheersbaar en verdraagbaar veiligheidsprofiel bij vrouwen met eerder behandelde recidiverende of gemetastaseerde baarmoederhalskanker. Na 10 maanden follow-up bereikten 7 vrouwen een CR = complete remissie en 17 procent een PR = gedeeltelijke remissie. 

Resultaten vertaald uit het abstract:

102 patiënten werden ingeschreven in een multicenter, open-label, eenarmige fase 2-studie tussen 12 juni 2018 en 11 april 2019; 101 patiënten kregen ten minste één dosis tisotumab vedotin.
De mediane follow-up op het moment van analyse was 10,0 maanden (IQR 6,1-13,0). Het bevestigde objectieve responspercentage was 24% (95% BI 16-33), met zeven (7%) volledige responsen en 17 (17%) gedeeltelijke responsen.

De meest voorkomende behandelingsgerelateerde bijwerkingen waren alopecia - haaruitval (38 [38%] van de 101 patiënten), epistaxis - bloedneus (30 [30%]), misselijkheid (27 [27%]), conjunctivitis (26 [26 %]), vermoeidheid ( 26 [26%]) en droge ogen (23 [23%]).
Behandelingsgerelateerde bijwerkingen van graad 3 of erger werden gemeld bij 28 (28%) patiënten en omvatten neutropenie (drie [3%] patiënten), vermoeidheid (twee [2%]), ulceratieve keratitis (twee [2%]) en perifere neuropathieën (twee [2%] elk met sensorische, motorische, sensorimotorische en perifere neuropathie).
Ernstige behandelingsgerelateerde bijwerkingen traden op bij 13 (13%) patiënten, waarvan de meest voorkomende perifere sensomotorische neuropathie (twee [2%] patiënten) en pyrexie (twee [2%]) waren.

Eén overlijden als gevolg van septische shock werd door de onderzoeker beschouwd als gerelateerd aan de therapie. Er werden drie sterfgevallen gemeld die geen verband hielden met de behandeling, waaronder één geval van ileus en twee onbekende oorzaken.

Het volledige studierapport is tegen betaling in te zien of te downloaden. Klik op de titel van het abstract.

 
. 2021 May;22(5):609-619.
 doi: 10.1016/S1470-2045(21)00056-5. Epub 2021 Apr 9.

Abstract

Background: Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor-directed antibody-drug conjugate, in this patient population.

Methods: This multicentre, open-label, single-arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396.

Findings: 102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow-up at the time of analysis was 10·0 months (IQR 6·1-13·0). The confirmed objective response rate was 24% (95% CI 16-33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment-related adverse events included alopecia (38 [38%] of 101 patients), epistaxis (30 [30%]), nausea (27 [27%]), conjunctivitis (26 [26%]), fatigue (26 [26%]), and dry eye (23 [23%]). Grade 3 or worse treatment-related adverse events were reported in 28 (28%) patients and included neutropenia (three [3%] patients), fatigue (two [2%]), ulcerative keratitis (two [2%]), and peripheral neuropathies (two [2%] each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment-related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two [2%] patients) and pyrexia (two [2%]). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes.

Interpretation: Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer.

Funding: Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups.

Conflict of interest statement

Declaration of interests RLC has received funding for consulting from AstraZeneca, Merck, Tesaro, Medivation, Clovis, GamaMabs, Genmab, Roche, Janssen, Agenus, Regeneron, and OncoQuest, and grant support from AstraZeneca, Merck, Clovis, Genmab, Roche, and Janssen. DL reports advisory board membership for Roche, Tesaro/GlaxoSmithKline, Clovis, Merck, PharmaMar, ImmunoGen, Genmab, Amgen, and AstraZeneca; grant support from Tesaro/GlaxoSmithKline, Merck, Roche, PharmaMar, and Clovis; consultancy for Clovis; travel support from Roche, PharmaMar, AstraZeneca, Tesaro/GlaxoSmithKline, AstraZeneca, and Amgen; and acting as principal investigator for registrational clinical trials for Roche, PharmaMar, Tesaro, Clovis, ImmunoGen, Genmab, AstraZeneca, and Merck. CG has received clinical trial institutional support from Genmab; is an advisory board member for Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Novartis, and Lilly; has received consultancy fees from GlaxoSmithKline and Roche; has received institutional grant support from Roche, PharmaMar, Merck Sharp & Dohme, and AstraZeneca; and has received travel support from Pfizer, PharmaMar, Ipsen, and Roche. AG-M has received consultancy fees or honoraria from AstraZeneca, Clovis, Genmab, ImmunoGen, Merck Sharp & Dohme, Amgen, Oncoinvent, Merck/Pfizer, Roche, Sotio, and Tesaro/GlaxoSmithKline, and institutional grant support from Roche and Tesaro/GlaxoSmithKline. LW has received honoraria from Genmab and Tesaro; travel support from Genmab, Tesaro, and medac; institutional grant support from Genmab and Roche; and fees for development of educational presentations from Roche, Pfizer, and medac. SP has received honoraria from Genmab, Roche, AstraZeneca, Merck Sharp & Dohme, GlaxoSmithKline, PharmaMar, Incyte, Pfizer, Merck, and Clovis, and research funding from Roche, AstraZeneca, Merck Sharp & Dohme, and Pfizer. FF has received institutional funding from Genmab for travel. AR has received consultancy fees from AstraZeneca, GlaxoSmithKline, Roche, PharmaMar, Clovis, and Amgen; institutional grant support from Roche, PharmaMar, and Eisai; honoraria from AstraZeneca, GlaxoSmithKline, Roche, PharmaMar, and Clovis; and travel support from Roche, AstraZeneca, and PharmaMar. SDV, MC, JRH, and MS are employees of and own stock in Genmab. LVN and MSLT are employees of and own stock in Seagen. RR is a former employee of and owns stock in Genmab. LM has received consultancy fees from Roche, Novartis, Pfizer, AstraZeneca, and GlaxoSmithKline, and institutional grant support from Tesaro. MM has received consultancy fees or honoraria from Genmab. BJM has received consultancy fees or honoraria from AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoID, Clovis, Deciphera, Eisai, Geistlich, Genmab, GOG Foundation, ImmunoGen, Immunomedics, Incyte, Iovance, Laekna Health Care, Merck, Mersana, Myriad, NuCana, OncoMed, OncoQuest, OncoSec, Perthera, Pfizer, Puma, Regeneron, Roche/Genentech, Seagen, Senti Biosciences, Starton Therapeutics, Takeda, Tesaro/GlaxoSmithKline, Vavotar Life Sciences, VBL, and Vigeo. IV has received institutional funding for the following: consultancy or honoraria from Amgen, AstraZeneca, Clovis Oncology, Carrick Therapeutics, Debiopharm, F Hoffmann-La Roche, Genmab, GlaxoSmithKline, ImmunoGen, Medical University of Vienna (Vienna, Austria), Millennium Pharmaceuticals, Merck Sharp & Dohme Belgium, Octimet Oncology, Oncoinvent, PharmaMar-Doctaforum Servicios SL, Roche, Sotio, Tesaro, Deciphera, and Verastem Oncology; institutional grant support from Amgen and Roche; institutional research support from Oncoinvent and Genmab; and institutional travel support from Amgen, AstraZeneca, Merck, Sharp & Dohme, Roche, and Tesaro. All other authors declare no competing interests.

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baarmoederhalskanker, Tisotumab vedotin, CR - complete remissie, PR - gedeeltelijke remissie, overall overleving, progressievrije ziekte


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