Evidence map›Paper›PMID 39198116›Full record

ArticleClinical breast cancer2024

Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience.

Jayasree Krishnan, Archit Patel, Arya Mariam Roy, Malak Alharbi, Ankita Kapoor, Song Yao, Thaer Khoury, Chi-Chen Hong, Nicole Held, Anumita Chakraborty and 8 more

Abstract readMulticenter Study
In one paragraph

Article in Clinical breast cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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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

18 authors.

Jayasree KrishnanDepartment of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Archit PatelDepartment of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Arya Mariam RoyDepartment of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Malak AlharbiDepartment of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY; Department of Internal Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia.
Ankita KapoorDepartment of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Song YaoDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Thaer KhouryDepartment of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Chi-Chen HongDepartment of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Nicole HeldDepartment of Medical Oncology, Medical College of Wisconsin, Milwaukee, WI.
Anumita ChakrabortyDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
Pawel KaliniskiDepartment of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Ahmed SalmanDepartment of Medical Oncology, Rochester Regional Health, Rochester, NY.
Kayla CatalfamoDepartment of Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Kristopher AttwoodDepartment of Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Vatsala KirtaniDepartment of Medical Oncology, Rochester Regional Health, Rochester, NY.
Saba S ShaikhDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Medical Oncology, University of Texas Health Science Center, San Antonio, TX.
Lubna N ChaudharyDepartment of Medical Oncology, Medical College of Wisconsin, Milwaukee, WI.
Shipra GandhiDepartment of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY. Electronic address: shipra.gandhi@roswellpark.org.

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI CANDACE S JOHNSON · 1985 to 2026
$116.6M
Targeting the Chemokine System to Sensitize Tumors to ImmunotherapyP01CA234212 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI BSHARA, WIAM · 2020 to 2024
$10.1M
Institutional Career DevelopmentKL2TR001413 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI DUBOCOVICH, MARGARITA L · 2015 to 2024
$4.2M
Stress-induced immunosuppression via downregulation of interferon in triple negative breast cancerK08CA279766 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Shipra Gandhi · 2024 to 2026
$915k
Identifying the role of interferon and interferon-regulated chemokines in stress-induced immunosuppression in triple negative breast cancerR03TR004607 · NCATS · ROSWELL PARK CANCER INSTITUTE CORP · PI GANDHI, SHIPRA · 2023 to 2023
$174k
NCATS NIH HHS KL2 TR001413NCATS NIH HHS R03 TR004607NCI NIH HHS K08 CA279766NCI NIH HHS P01 CA234212NCI NIH HHS P30 CA016056
6 · The paper itself

Abstract

backgroundPembrolizumab combined with neoadjuvant chemotherapy (NAC) is the current standard of care in early stage triple-negative breast cancer (TNBC) based on higher event-free survival and pathological complete response (pCR) in Keynote-522 (KN-522) clinical trial. However, this aggressive five-drug regimen is associated with increased risks for immune-related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen as well as factors predictive of pCR and irAEs.

methodsWe identified and abstracted data from 153 early-stage TNBC patients treated with the KN-522 regimen between July 1, 2021, and December 31, 2023, at 4 academic institutions in the U.S. Descriptive analysis was conducted, univariate and multivariate analyses were performed to identify factors associated with pCR and irAEs.

resultsThe median age was 52 years (interquartile range, 42-60years), with 66% White and 24% Black patients with stage I/II (67%), node-negative disease (58%), grade 3 (86%) tumors, and ≥1 comorbidities (68%). Approximately 21% discontinued pembrolizumab, because of toxicity; ∼50% received a lower relative dose intensity (RDI) of chemotherapy (dose reduction or discontinuation). Of the 153 patients, 99 (64.7%) achieved pCR and 83 (54%) experienced an irAE, with 18 (12%) having ≥ grade 3 irAE. The majority (90%) of the irAEs were observed during neoadjuvant phase. Stage I/II versus stage III disease (OR 1.55, CI 1.04-2.33, P = .03), age (OR 0.96, CI 0.93-0.99, P = .01) and full versus reduced RDI of NAC (OR 1.53, CI 1.04-2.26, P = .03) were associated with higher pCR rates on multivariate analyses. Fewer cycles of pembrolizumab were associated with a higher likelihood of irAEs (OR 1.52, CI 1.07-2.16, P = .02), likely explained by the early discontinuation and receipt of less than 8 cycles of pembrolizumab in patients who experienced irAEs.

conclusionsOur study validates the clinical efficacy of KN-522 regimen; however, we observed a higher incidence of irAEs (54%) in this real-world population. Lower stage and younger age were associated with higher likelihood of achieving pCR. Toxicity-related chemotherapy dose reduction or discontinuation was observed to adversely impact the likelihood of achieving pCR.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsNeoadjuvant TherapyTriple Negative Breast NeoplasmsAdultAntineoplastic Agents, ImmunologicalChemotherapy, AdjuvantFemaleHumansMiddle AgedNeoplasm StagingRetrospective StudiesAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalpembrolizumabChemotherapy dose reductionImmune related adverse eventsKeynote-522 regimenPathologic complete responseTriple negative breast cancer

Identifiers

PMID39198116
PMCPMC12838138

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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.