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1 februari 2020: lees ook dit artikel:
31 januari 2020: Bron: Journal of Clinical Oncology
Bij patienten met solide tumoren waaronder gevorderde nierkanker, gevorderde baarmoederkanker, gevorderde melanomen waarbij geen operatie kan worden uitgevoerd of andere behandelingen hebben gefaald en er verder geen opties meer zijn blijkt de combinatie van Lenvatinib (een zogeheten VEGFR remmer - vascular endothelial growth factor receptors) en immuuntherapie met een anti-PD medicijn, in dit geval pembrolizumab, toch nog een veelbelovende behandelingsoptie.
In deze grafiek zijn de deelnemende patienten per vorm van kanker vermeld, hun status en of ze wel of niet PD-L1 expressie hadden ja of nee.:
Uit het abstract overgenomen de resultaten op 2-jaars meting van een complete of gedeeltelijke remissie van 50 procent of meer:
- nierkanker - RCC: 63% (19/30; 95% CI, 43.9% to 80.1%);
- buikvlieskanker: 52% (12/23; 95% CI, 30.6% to 73.2%);
- melanomen: 48% (10/21; 95% CI, 25.7% to 70.2%);
- Hoofd-halstumoren - SCCHN: 36% (8/22; 95% CI, 17.2% to 59.3%);
- Nier-kleincellige longkanker - NSCLC: 33% (7/21; 95% CI, 14.6% to 57.0%);
- urinewegenkanker: 25% (5/20; 95% CI, 8.7% to 49.1%).
De meest voorkomende behandelingsgerelateerde bijwerkingen waren vermoeidheid (58%), diarree (52%), hypertensie - te hoge bloeddruk (47%) en hypothyreoïdie = tekort aan schildklierhormonen (42%).
Het volledige studierapport: Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors is gratis in te zien.
Hier het abstract en daaronder de referentielijst:
The combination of lenvatinib plus pembrolizumab had promising efficacy among patients with selected solid tumors, with a manageable safety profile
Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors
Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
ABSTRACT
Modulation of vascular endothelial growth factor–mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. We report results from the dose-finding and initial phase II expansion of a phase Ib/II study of lenvatinib plus pembrolizumab in patients with selected advanced solid tumors.
Eligible patients had metastatic renal cell carcinoma (RCC), endometrial cancer, squamous cell carcinoma of the head and neck (SCCHN), melanoma, non–small-cell lung cancer (NSCLC), or urothelial cancer. The primary objective of phase Ib was to determine the maximum tolerated dose (MTD) for lenvatinib plus pembrolizumab (200 mg intravenously every 3 weeks). In the preplanned phase II cohort expansion, the primary objective was objective response rate at week 24 (ORRweek 24) at the recommended phase II dose.
Overall, 137 patients were enrolled during phase Ib (n = 13) and the initial phase II expansion (n = 124). Two dose-limiting toxicities (DLTs; grade 3 arthralgia and grade 3 fatigue) were reported in the initial dose level (lenvatinib 24 mg/d plus pembrolizumab). No DLTs were observed in the subsequent dose–de-escalation cohort, establishing the MTD and recommended phase II dose at lenvatinib 20 mg/d plus pembrolizumab. ORRweek24 was as follows: RCC, 63% (19/30; 95% CI, 43.9% to 80.1%); endometrial cancer, 52% (12/23; 95% CI, 30.6% to 73.2%); melanoma, 48% (10/21; 95% CI, 25.7% to 70.2%); SCCHN, 36% (8/22; 95% CI, 17.2% to 59.3%); NSCLC, 33% (7/21; 95% CI, 14.6% to 57.0%); and urothelial cancer 25% (5/20; 95% CI, 8.7% to 49.1%). The most common treatment-related adverse events were fatigue (58%), diarrhea (52%), hypertension (47%), and hypothyroidism (42%).
Lenvatinib plus pembrolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with selected solid tumor types.
Conception and design: All authors
Provision of study materials or patients: Matthew H. Taylor, Robert J. Motzer, Chung-Han Lee, Vicky Makker, Drew Rasco
Collection and assembly of data: Matthew H. Taylor, Robert J. Motzer, Chung-Han Lee, Vicky Makker, Drew Rasco
Data analysis and interpretation: All authors
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Consulting or Advisory Role: Bristol-Myers Squibb, Eisai, Array BioPharma, Loxo, Bayer, ArQule, Blueprint Medicines, Novartis, Sanofi/Genzyme
Speakers' Bureau: Bristol-Myers Squibb, Eisai
Consulting or Advisory Role: Exelixis, Eisai, Amgen, Bristol-Myers Squibb
Research Funding: Pfizer (Inst), Eisai (Inst), Bristol-Myers Squibb (Inst), Calithera Biosciences (Inst), Exelixis (Inst)
Travel, Accommodations, Expenses: Eisai
Travel, Accommodations, Expenses: Calithera Biosciences
Honoraria: Eisai, Merck
Consulting or Advisory Role: Eisai, Merck, Karyopham, Takeda, ArQule
Research Funding: Lilly, AstraZeneca, Eisai, Merck, Takeda, Bristol-Myers Squibb
Travel, Accommodations, Expenses: Eisai, Merck, Karyopharm Therapeutics
Other Relationship: IBM
Consulting or Advisory Role: Boehringer Ingelheim, Lilly
Research Funding: Celgene (Inst), Millennium (Inst), Rexahn Pharmaceuticals (Inst), Five Prime Therapeutics (Inst), Pharmacyclics (Inst), Asana Biosciences (Inst), Eisai (Inst), Aeglea Biotherapeutics (Inst), Merck (Inst), Ascentage Pharma (Inst), Macrogenics (Inst), Apexian Pharmaceuticals (Inst), Birdie (Inst), AbbVie (Inst), Constellation Pharmaceuticals (Inst), Syndax (Inst), Astex Pharmaceuticals (Inst), Compugen (Inst), Coordination Therapeutics (Inst), GlaxoSmithKline (Inst), Incyte (Inst)
Travel, Accommodations, Expenses: Asana Biosciences
Employment: Eisai
Employment: Eisai
Employment: Eisai
Employment: Eisai, RRD International (I)
Consulting or Advisory Role: Pfizer, Novartis, Eisai, Exelixis, Merck, Genentech, Incyte, Lilly
Research Funding: Pfizer (Inst), Bristol-Myers Squibb (Inst), Eisai (Inst), Novartis (Inst), Genentech (Inst)
No other potential conflicts of interest were reported.
ACKNOWLEDGMENT
We thank the patients, their families, the investigators, and the teams who participated in this trial. We also thank Emmett Schmidt, MD, PhD (Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ); Marcia Brose, MD, PhD (Department of Otorhinolaryngology – Head and Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA); Peter Kubiak, PhD (Eisai Inc., Woodcliff Lake, NJ); and Lea Dutta, Pharm.D (Eisai Inc., Woodcliff Lake, NJ) for their contributions. This study was funded by Eisai Inc., Woodcliff Lake, NJ, and was also supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by a Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). Medical writing and editorial support was provided by Oxford PharmaGenesis Inc., Newtown, PA, and was funded by Eisai Inc., Woodcliff Lake, NJ, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ.
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