Evidence map›Paper›PMID 33544407›Full record

Trial reportCancer medicine2021

A phase 2 trial of trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable metastatic colorectal cancer.

Manish R Patel, Gerald S Falchook, Kensuke Hamada, Lukas Makris, Johanna C Bendell

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02860546 (A Phase 2 Study With Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients With Microsatellite Stable Refractory Metastatic Colorectal Cancer), which is not on this map. Cited by 31 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 3 pooled it
6.8field-weighted citation impact, top 2% of its field
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.

NCT02860546 phase2completednot on this map

A Phase 2 Study With Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients With Microsatellite Stable Refractory Metastatic Colorectal Cancer

TypeinterventionalSponsorTaiho Oncology, Inc.Ran2016 to 2017Enrolled18ConditionsRefractory Metastatic Colorectal CancerArmsTAS-102, nivolumab
3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 55 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Manish R PatelFlorida Cancer Specialists and Sarah Cannon Research Institute, Sarasota, Florida, USA.
Gerald S FalchookSarah Cannon Research Institute at HealthONE, Denver, Colorado, USA.ORCID 0000-0001-9165-2191
Kensuke HamadaTaiho Oncology, Inc, Princeton, New Jersey, USA.
Lukas MakrisStathmi, Inc, New Hope, Pennsylvania, USA.ORCID 0000-0001-6963-0105
Johanna C BendellSarah Cannon Research Institute and Tennessee Oncology, Nashville, Tennessee, USA.ORCID 0000-0001-9426-5891
Sarah Cannon · USTaiho Oncology (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMicrosatellite-stable (MSS) colorectal cancer (CRC) tends to be poorly immunogenic, with limited treatment options. In MSS CRC xenograft models, trifluridine/tipiracil (FTD/TPI) plus programed death 1 inhibitors resulted in synergistic antitumor activity and increased tumor immunogenicity. This phase 2 study evaluated FTD/TPI plus nivolumab in patients with MSS metastatic CRC.

methodsThis single-arm, safety lead-in study used a Simon's two-stage design (enrolling 6 patients in the safety lead-in, proceeding to stage 2 if ≥2 of the first 15 patients achieved a partial or complete response per immune-related response criteria [irRC] within 6 months). Patients with histologically proven MSS mCRC, and disease progression after ≥2 prior chemotherapy regimens received FTD/TPI (35 mg/m

resultsBetween August 2016 and January 2017, 18 patients (50% men; median age 56.5 years) were enrolled; 72% had colon cancer and 56% had KRAS mutations. All patients received treatment (median, 2.5 cycles [range, 1-8]). No dose-limiting toxicities were observed in the study. The most frequent adverse events (AEs) of any cause and grade were nausea (67%), diarrhea (61%), and neutropenia (50%); 13 patients (72%) experienced grade ≥3 AEs. No patients discontinued treatment because of AEs. No patient achieved a tumor response (either per Response Evaluation Criteria in Solid Tumors [RECIST] or irRC), and the study did not progress to the second stage. Stable disease was achieved in 8 patients per irRC and in 10 patients per RECIST. Median progression-free survival was 2.2 months (95% CI, 1.8-6.0 months) per irRC and 2.8 months (95% CI, 1.8-5.1 months) per RECIST.

conclusionPatients with refractory MSS metastatic CRC failed to experience clinical benefit with FTD/TPI plus nivolumab, although safety data in this population indicated tolerability and feasibility of this combination. TRIAL REGISTRATION NUMBER: NCT02860546.

Indexed as

Drug Resistance, NeoplasmMicrosatellite RepeatsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDrug CombinationsFemaleHumansMaleMiddle AgedNeoplasm MetastasisNivolumabPyrrolidinesSurvival RateThymineDrug CombinationsNivolumabPyrrolidinesThymineTrifluridinetrifluridine tipiracil drug combinationchemotherapyclinical trialscolorectal cancerimmunotherapy

Identifiers

PMID33544407
PMCPMC7926002
OpenAlexW3128854694

What OpenQuestion holds

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Registered trials

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.