Evidence map›Paper›PMID 41223631›Full record

ArticleESMO open2025

Phase I trial of neratinib plus palbociclib in advanced cancers with HER family alterations.

S A Piha-Paul, C Tseng, H T Tran, S Fu, E E Dumbrava, T A Yap, A Naing, J Lim, M B Murphy, D L Ramirez and 3 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

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.

S A Piha-PaulInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: spihapau@mdanderson.org.
C TsengInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA.
H T TranThoracic, Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
S FuInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA.
E E DumbravaInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA.
T A YapInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA; Therapeutics Discovery Division, University of Texas MD Anderson Cancer Center, Houston, USA; The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston, USA.
A NaingInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA.
J LimPharmacy Clinical Programs, Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, USA.
M B MurphyDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
D L RamirezDepartment of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
P T SolimanDepartment of Gynecology Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, USA.
A K SoodDepartment of Gynecology Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, USA.
F Meric-BernstamInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA; The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston, USA; Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Convalescent Plasma to Limit Coronavirus Associated ComplicationsUL1TR003167 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARP, DANIEL D, MCPHERSON, DAVID D · 2019 to 2023
$45.3M
NCATS NIH HHS UL1 TR003167NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundAberrations in the human epidermal growth factor receptor (HER) and cyclin-dependent kinase 4/6 pathways drive tumor growth. While neratinib, a pan-HER kinase inhibitor, and palbociclib, a cyclin-dependent kinase 4/6 inhibitor, are effective in targeting these pathways individually, resistance to monotherapy limits durability of benefit. Herein, we sought to determine the feasibility of combining neratinib and palbociclib. PATIENTS AND

methodsThis single-center phase I trial enrolled patients with advanced solid tumors harboring HER alterations. Primary objectives were to establish maximum tolerated dose and characterize dose-limiting toxicities. Secondary objectives included pharmacokinetic assessment and preliminary antitumor efficacy.

resultsThirty-five patients were enrolled (median age, 61.5 years; median four prior therapy lines); 74% were female, and all had an Eastern Cooperative Oncology Group performance status of 0-1. Breast cancer was the most common tumor type, with HER2 amplification being the most predominate alteration. Common grade (G) 1-2 treatment-related adverse events included diarrhea (80%), leukopenia (57.1%), neutropenia (48.6%), and thrombocytopenia (48.6%). G ≥3 treatment-related adverse events affecting ≥20% of patients were neutropenia (37.1%) and leukopenia (22.9%). Dose-limiting toxicities were G3 febrile neutropenia and G3 febrile neutropenia with hepatitis. The maximum tolerated dose was neratinib 240 mg daily for 28 days and palbociclib 125 mg daily for a 3 weeks on/1 week off schedule. Among 30 response-assessable patients, the objective response rate was 16.7% (five partial responses) and three patients exhibited prolonged stable disease ≥16 weeks, yielding a clinical benefit rate of 26.7%. Pharmacokinetic analysis indicated a drug-drug interaction between neratinib and palbociclib via the CYP3A4 metabolism pathway, leading to decreased clearance and increased plasma exposure of both drugs.

conclusionCombination therapy with neratinib and palbociclib demonstrated a favorable safety profile and clinical benefit rate in patients with HER-driven alterations. Pharmacokinetic analysis revealed a CYP3A4-mediated drug-drug interaction, leading to reduced clearance and increased plasma exposure of both agents, underscoring the importance of considering metabolic interactions in future clinical development.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsNeoplasmsPiperazinesPyridinesQuinolinesAdultAgedAged, 80 and overErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleHumansMaleMaximum Tolerated DoseMiddle AgedProtein Kinase InhibitorsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesErbB ReceptorsneratinibpalbociclibPiperazinesProtein Kinase InhibitorsPyridinesQuinolinesEGFRHER-2HER-3HER-4neratinibpalbociclib

Identifiers

PMID41223631
PMCPMC12657739

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.