Evidence map›Paper›PMID 41946829›Full record

Trial reportBritish journal of cancer2026

Safety and efficacy of lapatinib, binimetinib, and vinorelbine for RAS mutant metastatic colorectal cancer: results of the RASTRIC Phase I/II trial.

Maarten A Huismans, Eelke H Gort, Lisa T van der Heijden, Sermin M Guven Mese, Helena M Klein Wolterink, Manon N G J A Braat, Sjoerd G Elias, Filip Y F L de Vos, Lot A Devriese, Henk M W Verheul and 7 more

Erratum issuedAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Maarten A HuismansDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-1556-0820
Eelke H GortDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Lisa T van der HeijdenDepartment of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Sermin M Guven MeseDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Helena M Klein WolterinkDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Manon N G J A BraatDepartment of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Sjoerd G EliasDepartment of Epidemiology, Julius Center for Health Sciences and Primary Care, Utrecht University, Utrecht, the Netherlands.
Filip Y F L de VosDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-9082-5991
Lot A DevrieseDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Henk M W VerheulDepartment of Medical Oncology, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, the Netherlands.
Frans L OpdamEarly Drug Development Center, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Miriam KoopmanDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-1550-1978
Hilde H NienhuisDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Heleen A CrommelinDepartment of Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Hugo J G SnippertCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-4189-5213
Alwin D R HuitemaDepartment of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Jeanine M L RoodhartDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. j.roodhart@umcutrecht.nl.ORCID http://orcid.org/0000-0003-1398-8970

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTreatment options for RAS-mutant metastatic colorectal cancer (mCRC) remain limited. Based on preclinical work with patient-derived organoids, we investigated a triple therapy of binimetinib, lapatinib, and vinorelbine in a Phase I/II trial.

methodsForty patients with RAS-mutant mCRC received escalating doses of binimetinib and lapatinib with vinorelbine 17.5 mg/m² in three-weekly schedules. Phase I aimed to determine the Recommended Phase II Regimen (RP2R), while Phase II evaluated Overall Response Rate using Simon's two-stage design. Pharmacokinetic analyses were performed on cycle 1 day 3.

resultsThe Maximum Tolerated Dose was established at lapatinib 750 mg QD and binimetinib 30 mg BID (both 5 days on/2 days off), with vinorelbine 17.5 mg/m² on days 3 and 10 every 21 days. Toxicities included diarrhoea (75%), rash (65%), and increased CPK (57%). Among 33 evaluable patients, no objective responses occurred, with 9 (27%) achieving stable disease, lasting beyond 3 months (maximum: 297 days) in three patients. Pharmacokinetics showed dose-proportional exposure for binimetinib but not lapatinib. Binimetinib absorption may be affected by colostomy and loperamide-induced constipation.

conclusionsThe triple combination showed moderate tolerability and termination occurred after the first stage of Phase II due to insufficient efficacy. Our findings highlight challenges in translating organoid-derived drug combinations to clinical practice. CLINICAL

trial registrationEUDRACT: 2019-004987-23.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsLapatinibras ProteinsVinorelbineAdultAgedBenzimidazolesFemaleHumansMaleMaximum Tolerated DoseMiddle AgedMutationBenzimidazolesbinimetinibLapatinibras ProteinsVinorelbine

Identifiers

PMID41946829
PMCPMC13226703

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.