31 januari 2023
Zie ook literatuurlijst voeding en voedingssupplementen en weinig belastende behandelingen specifiek bij darmkanker van arts-bioloog drs. Engelbert Valstar.

31 januari 2023: Bron: Journal of Clinical Oncology Published online January 09, 2023.
In een fase II open-label klinische studie (N = 33 patiënten) werden patiënten met gelokaliseerde inoperabele solide tumoren met (MSI-H) hoog-risico operabele microsatelliet instabiliteit /deficiency mismatch repair (dMMR)  behandeld met vooraf aan een operatie immuuntherapie met pembrolizumab (KEYTRUDA) gedurende 6 maanden. De meerderheid van de patiënten (54%) had darmkanker met adenocarcinoom.

Bij 49% van de patiënten (N = 17) die na de immuuntherapie een operatie ondergingen, werd bij 65% van de patiënten een pathologische complete respons (pCR) waargenomen. Bij patiënten met darmkanker was het complete respons (pCR) -percentage 79%.
Van de 18 patiënten die geen operatie ondergingen, vertoonden er slechts 2 progressie van hun ziekte daarna. Er werden geen nieuwe ernstige bijwerkingen waargenomen.

Coinclusie van de onderzoekers is dan ook:  

Deze bevindingen geven aan dat neoadjuvante pembrolizumab bij patiënten met een breed scala aan MSI-H/dMMR solide tumoren resulteert in een hoog pathologisch compleet responspercentage, wat suggereert dat dit een goede benadering kan zijn voor dMMR-tumoren om orgaanbehoud mogelijk te maken.

Het volledige studieverslag is tegen betaling in te zien. Hier het abstract van de studie:

Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space.

This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. To continue on study, patients are required to have radiographic or clinical benefit. The coprimary end points are safety and pathologic complete response. Key secondary end points are response rate and organ-sparing at one year for patients who declined surgery. Exploratory analyses include interrogation of the tumor immune microenvironment using imaging mass cytometry.

A total of 35 patients were enrolled, including 27 patients with colorectal cancer and eight patients with noncolorectal cancer. Among 33 evaluable patients, best overall response rate was 82%. Among 17 (49%) patients who underwent surgery, the pathologic complete response rate was 65%. Ten patients elected to receive one year of pembrolizumab followed by surveillance without surgical resection (median follow-up of 23 weeks [range, 0-54 weeks]). An additional eight did not undergo surgical resection and received less than 1 year of pembrolizumab. During the study course of the trial and subsequent follow-up, progression events were seen in six patients (four of whom underwent salvage surgery). There were no new safety signals. Spatial immune profiling with imaging mass cytometry noted a significantly closer proximity between granulocytic cells and cytotoxic T cells in patients with progressive events compared with those without progression.

Neoadjuvant pembrolizumab in dMMR/MSI-H cancers is safe and resulted in high rates of pathologic, radiographic, and endoscopic response, which has implications for organ-sparing strategies.

© 2023 by American Society of Clinical Oncology

  • Key Objective

  • Among patients with a diverse range of localized, solid microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) tumors, can preoperative pembrolizumab result in pathologic complete response (tumor eradication)?

  • Knowledge Generated

  • Seventeen patients (49% of study population) underwent surgical resection and demonstrated a high pathologic complete response rate of 65%. The remaining 18 patients (51% of study population) pursued nonoperative management with durable responses in the majority, suggesting that definitive nonsurgical management with the use of immunotherapy in MSI-H/dMMR tumors is promising and warrants further exploration.

  • Relevance (E.M. O'Reilly)

  • This study adds to the growing body of evidence that endorses the role of anti–programmed cell death protein-1 antibody therapy in GI cancers with dMMR/MSI-H, where deep and major pathologic responses are observed in a substantial majority of patients with localized disease.*

    *Relevance section written by JCO Associate Editor Eileen M. O'Reilly, MD.


Presented orally at ESMO Congress, Paris Expo Porte de Versailles, France, September 19, 2021. Presented as a poster at ASCO Annual Conference, June 2021.


Supported by CCSG P30 CA016672, SPORE P50CA221707, Merck (Recipient: M.J.O.), and Kavanagh Family Foundation (Recipient: J.V.T.).



Conception and design: Kaysia Ludford, Wei Qiao, Scott Kopetz, Michael J. Overman

Financial support: Michael J. Overman

Administrative support: Michael J. Overman

Provision of study materials or patients: Nicole D. Fleming, Michael S. Lee, Y. Nancy You, Matthew M. Tillman, Benny Johnson, Eduardo Vilar, Arvind Dasari, Xuan Yuan, Wai Chin Foo, Dipen Maru, Scott Kopetz, Michael J. Overman

Collection and assembly of data: Kaysia Ludford, Won Jin Ho, Jane V. Thomas, Mariela Blum Murphy, Nicole D. Fleming, Michael S. Lee, Y. Nancy You, Matthew M. Tillman, Carlos Kamiya-Matsuoka, Selvi Thirumurthi, Benny Johnson, Eduardo Vilar, Arvind Dasari, Sarah Shin, Alexei Hernandez, Xuan Yuan, Hongqui Yang, Wai Chin Foo, Dipen Maru, Scott Kopetz, Michael J. Overman

Data analysis and interpretation: Kaysia Ludford, Won Jin Ho, Jane V. Thomas, Kanwal P.S. Raghav, Nicole D. Fleming, Michael S. Lee, Brandon G. Smaglo, Y. Nancy You, Matthew M. Tillman, Carlos Kamiya-Matsuoka, Craig Messick, Benny Johnson, Arvind Dasari, Sarah Shin, Wai Chin Foo, Dipen Maru, Scott Kopetz

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/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Kaysia Ludford

Research Funding: Merck (Inst)

Won Jin Ho

Honoraria: Standard Biotools

Consulting or Advisory Role: Exelixis

Research Funding: Sanofi (Inst), NeoTX (Inst)

Patents, Royalties, Other Intellectual Property: I hold patents and receive royalties from Rodeo Therapeutics

Kanwal P.S. Raghav

Consulting or Advisory Role: AstraZeneca, Bayer, Eisai, Daiichi Sankyo, Seattle Genetics

Speakers' Bureau: Bayer

Research Funding: Bayer (Inst), Roche/Genentech (Inst), Guardant Health (Inst), Daiichi Sankyo/Astra Zeneca (Inst), HiberCell (Inst), Merck Serono (Inst)

Mariela Blum Murphy

Research Funding: Bristol Myers Squibb (Inst), Genentech/Roche (Inst)

Nicole D. Fleming

Consulting or Advisory Role: Tesaro, Pfizer, GlaxoSmithKline, Immunogen

Michael S. Lee

Consulting or Advisory Role: Pfizer, Imvax, G1 Therapeutics, Delcath Systems

Research Funding: Arcus Biosciences (Inst), Erasca Inc (Inst), Repare Therapeutics (Inst), Merck (Inst), TriSalus Life Sciences (Inst), Boehringer Ingelheim (Inst), Xilis (Inst), EpimAb BioTherapeutics (Inst)

Brandon G. Smaglo

Speakers' Bureau: Taiho Pharmaceutical, Sirtex Medical

Travel, Accommodations, Expenses: Marker Therapeutics

Benny Johnson

Consulting or Advisory Role: Gritstone Bio, Incyte, Taiho Oncology, Insmed, Pfizer

Research Funding: Bristol Myers Squibb (Inst), Syntrix Biosystems (Inst), Gateway Foundation (Inst)

Eduardo Vilar

Consulting or Advisory Role: Janssen Research & Development, Recursion Pharmaceuticals, Guardant Health

Research Funding: Janssen Research & Development

Patents, Royalties, Other Intellectual Property: The University of Texas MD Anderson Cancer Center, Vilar E, Wu W, Katayama H, Hanash S, Bommi P. Methods for Prognosing, Diagnosing, and Treating Colorectal Cancer, United States, 63/152,751, 2/23/2021, Filed (Provisional), The University of Texas MD Anderson Cancer Center, Vilar E, Chang K, Wu W, Bowen CM, Sinha K. Methods and Compositions Comprising MHC Class I Peptides, United States, 63/171,137, 4/6/2021, Filed (Provisional)

Travel, Accommodations, Expenses: Janssen Research & Development

Arvind Dasari

Consulting or Advisory Role: Novartis, Voluntis, Personalis, Crinetics Pharmaceuticals

Research Funding: Eisai, Hutchison MediPharma, Merck, Guardant Health

Dipen Maru

Honoraria: GSB Pharma (I)

Speakers' Bureau: Clinical Care Options, Pfizer

Research Funding: Daiichi Sankyo/UCB Japan

Uncompensated Relationships: Bristol Myers Squibb/Medarex

Scott Kopetz

Stock and Other Ownership Interests: Lutris, Iylon, Frontier Medicines, Xilis, Navire

Consulting or Advisory Role: Genentech, EMD Serono, Merck, Holy Stone Healthcare, Novartis, Lilly, Boehringer Ingelheim, AstraZeneca/MedImmune, Bayer Health, Redx Pharma, Ipsen, HalioDx, Lutris, Jacobio, Pfizer, Repare Therapeutics, Inivata, GlaxoSmithKline, Jazz Pharmaceuticals, Iylon, Xilis, AbbVie, Amal Therapeutics, Gilead Sciences, Mirati Therapeutics, Flame Biosciences, Servier, Carina Biotech, Bicara Therapeutics, Endeavor BioMedicines, Numab, Johnson & Johnson/Janssen, Genomic Health, Frontier Medicines, Replimune, Taiho Pharmaceutical, Cardiff Oncology, Ono Pharmaceutical, Bristol Myers Squibb/Medarex, Amgen, Tempus, Foundation Medicine, Harbinger Oncology Inc, Takeda, CureTeq, Zentalis, Black Stone Therapeutics, NeoGenomics Laboratories, Accademia Nazionale Di Medicina

Research Funding: Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, MedImmune, Novartis, Amgen, Lilly, Daiichi Sankyo

Michael J. Overman

Consulting or Advisory Role: Bristol Myers Squibb, Roche/Genentech, Gritstone Bio, MedImmune, Novartis, Promega, Spectrum Pharmaceuticals, Array BioPharma, Janssen, Pfizer, 3D Medicines, Merck, Eisai

Research Funding: Bristol Myers Squibb, Merck, Roche, MedImmune

No other potential conflicts of interest were reported.

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