Evidence map›Paper›PMID 35641211›Full record

ArticleThe oncologist2022

FDA Approval Summary: Revised Indication and Dosing Regimen for Ponatinib Based on the Results of the OPTIC Trial.

E Dianne Pulte, Haiyan Chen, Lauren S L Price, Ramadevi Gudi, Hongshan Li, Olanrewaju O Okusanya, Lian Ma, Lisa Rodriguez, Jonathon Vallejo, Kelly J Norsworthy and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The oncologist, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
6.7field-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.

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

22 citing papers in PubMed, 42 citations in OpenAlex.

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  18. Real-world Management of CML: Outcomes and Treatment Patterns.Current hematologic malignancy reports · 2023
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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

13 authors at 2 institutions in 1 country.

E Dianne PulteCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Haiyan ChenCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Lauren S L PriceCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Ramadevi GudiCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Hongshan LiCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Olanrewaju O OkusanyaCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Lian MaCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Lisa RodriguezCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Jonathon VallejoCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Kelly J NorsworthyCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
R Angelo de ClaroCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Marc R TheoretOncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Richard PazdurCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

On December 18, 2020, US Food and Drug Administration (FDA) approved a supplemental application for ponatinib extending the indication in patients with chronic-phase chronic myeloid leukemia (CP-CML) to patients with resistance or intolerance of at least 2 prior kinase inhibitors. Ponatinib was initially approved in December 2012 but was briefly voluntarily withdrawn due to serious safety concerns including the risk of arterial occlusive events (AOE). It returned to the market in December 2013 with an indication limited to patients with T315I mutation or for whom no other tyrosine kinase inhibitor (TKI) therapy was indicated with revised warnings and precautions. A post-marketing requirement was issued to identify the optimal safe and effective dose for CP-CML. Thus, the OPTIC trial was performed, which randomized patients to 1 of 3 doses, 45 mg, 30 mg, or 15 mg, with a dose reduction to 15 mg on achievement of MR2 (BCR-ABLIS ≤1%). Patients enrolled were treated with at least 2 prior TKIs or had a T315I mutation. Patients with a history of clinically significant, uncontrolled, or active cardiovascular disease were excluded. Efficacy was established on an interim analysis based on the rate of MR2 at 12 months in the modified intent-to-treat population of 261 patients, with 88, 86, and 87 patients in the 45, 30, and 15 mg cohorts, respectively. With a median follow-up of 28 months, the rate of achievement of MR2 at 12 months was 42%, 28%, and 24% in the respective cohorts. The safety profile was consistent with that observed in prior evaluations of ponatinib with notable adverse reactions including pancreatitis, hypertension, hyperlipidemia, liver dysfunction, and AOE. Of patients treated at the 45/15 mg dose, AOEs were seen in 13%, with a higher rate being observed in patients age 65 or older compared to younger patients. A readjudication of AOEs seen on the prior pivotal phase 2 study resulted in a rate of 26%. Overall, the results supported a modification of the recommended dose for patients with CP-CML to 45 mg until the achievement of MR2 followed by a reduction to 15 mg. The expansion of the indication to patients with exposure to 2 prior TKIs was approved given data showing that ponatinib could be successfully used for the treatment of this population with appropriate monitoring and screening for risk factors.

Indexed as

Antineoplastic AgentsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveAgedDrug Resistance, NeoplasmFusion Proteins, bcr-ablHumansImidazolesProtein Kinase InhibitorsPyridazinesUnited StatesUnited States Food and Drug AdministrationAntineoplastic AgentsFusion Proteins, bcr-ablImidazolesponatinibProtein Kinase InhibitorsPyridazineschronic-phase chronic myeloid leukemiaFDA approvalponatinib

Identifiers

PMID35641211
PMCPMC8895737
OpenAlexW4206805071

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.