Evidence map›Paper›PMID 40165400›Full record

Trial reportCancer medicine2025

Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib.

Ajibade Ashaye, Ling Shi, Ibrahim Aldoss, Pau Montesinos, Pankit Vachhani, Vanderson Rocha, Cristina Papayannidis, Jessica T Leonard, Maria R Baer, Jose-Maria Ribera and 4 more

Registry-linked trialAbstract readClinical Trial, Phase IIIComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03589326 (A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT03589326 phase3active not recruitingnot on this map

A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

TypeinterventionalSponsorTakedaRan2018 to 2027Enrolled245ConditionsPhiladelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)ArmsPonatinib, Imatinib, Vincristine, Dexamethasone, Cytarabine
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

14 authors.

Ajibade AshayeTakeda Development Center Americas Inc., Cambridge, Massachusetts, USA.ORCID https://orcid.org/0000-0003-3731-0769
Ling ShiEvidera Inc., Bethesda, Maryland, USA.
Ibrahim AldossCity of Hope National Medical Center, Duarte, California, USA.ORCID https://orcid.org/0000-0001-9564-4498
Pau MontesinosHospital Universitari i Politècnic La Fe, Valencia, Spain.
Pankit VachhaniUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID https://orcid.org/0000-0001-9779-6217
Vanderson RochaInstituto Do Câncer Do Estado de São Paulo, São Paulo, Brazil.
Cristina PapayannidisIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "L. e A. Seràgnoli,", Bologna, Italy.
Jessica T LeonardOregon Health and Science University, Portland, Oregon, USA.
Maria R BaerUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Jose-Maria RiberaICO-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Badalona, Spain.ORCID https://orcid.org/0000-0003-1042-6024
James McCloskeyHackensack University Medical Center, Hackensack, New Jersey, USA.
Jianxiang WangInstitute of Hematology & Blood Diseases Hospital of CAMS & PUMC, Tianjin, China.
Deepali RaneTakeda Development Center Americas Inc., Cambridge, Massachusetts, USA.
Shien GuoEvidera Inc., Bethesda, Maryland, USA.

Funding

Takeda Development Centers Americas Inc., Cambridge, MA, USA
6 · The paper itself

Abstract

backgroundIn the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.

methodsOverall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment-emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow-up). Q-TWiST was calculated as the sum of health utility-weighted restricted mean durations of the three states. A relative Q-TWiST gain of ≥ 10% was considered clinically important. Sensitivity analyses were conducted by varying TOX and REL utilities, follow-up time, and the TOX definition (using grade 2+ TEAEs or patient-perceived treatment tolerability assessed by the FACT-GP5).

resultsAmong all randomized patients (ponatinib n = 164, imatinib n = 81), restricted mean OS was similar between arms (1082.2 vs. 1024.8 days; p = 0.373). In the base-case analysis, mean TWiST was 214.5 days longer with ponatinib versus imatinib (95% CI 70.3-358.7; p = 0.004), REL was shorter by 175.9 days (325.4-26.5; p = 0.021), and TOX was not significantly different between arms (p = 0.228). The relative Q-TWiST gain (10.98%) was clinically important. Sensitivity analyses consistently supported the robustness of the base-case findings.

conclusionPonatinib may prolong quality-adjusted survival compared with imatinib, supporting the benefit-risk profile of ponatinib as a front-line treatment for Ph+ ALL.

trial registrationNCT03589326.

Indexed as

Antineoplastic AgentsImatinib MesylateImidazolesPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Kinase InhibitorsPyridazinesAdultAgedFemaleHumansMaleMiddle AgedPhiladelphia ChromosomeTreatment OutcomeYoung AdultAntineoplastic AgentsImatinib MesylateImidazolesponatinibProtein Kinase InhibitorsPyridazinesacute lymphoblastic leukemiaimatinibPhiladelphia chromosome‐positiveponatinibQ‐TWiST analysisquality of lifetyrosine kinase inhibitor

Identifiers

PMID40165400
PMCPMC11958597

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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.