Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis

Jacob Aptekar; Rahul Jain; Beata Korytowsky; Afrah Shafquat; Jacob Hendershot; Aniketh Talwai; Yahav Itzkovich; Sukhmani K. Padda

doi:10.1016/j.lungcan.2024.107854

Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis

Jacob Aptekar, Rahul Jain, Beata Korytowsky, Afrah Shafquat, Jacob Hendershot, Aniketh Talwai, Yahav Itzkovich, Sukhmani K. Padda

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVES: Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials.

MATERIALS AND METHODS: Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status.

RESULTS: A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively.

CONCLUSION: These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.

Original language	English
Article number	107854
Journal	Lung Cancer
Volume	193
Early online date	May 10 2024
DOIs	https://doi.org/10.1016/j.lungcan.2024.107854
State	Published - Jul 2024

Keywords

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Brain Neoplasms/secondary
Carcinoma, Non-Small-Cell Lung/drug therapy
Clinical Trials, Phase III as Topic
Disease Progression
Docetaxel/therapeutic use
Female
Humans
Lung Neoplasms/drug therapy
Male
Middle Aged
Mutation
Neoplasm Staging
Proto-Oncogene Proteins p21(ras)/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.lungcan.2024.107854

Cite this

@article{780a566f48234e0b8270e29bf5b90c3a,

title = "Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis",

abstract = "OBJECTIVES: Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials.MATERIALS AND METHODS: Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status.RESULTS: A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively.CONCLUSION: These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.",

keywords = "Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Brain Neoplasms/secondary, Carcinoma, Non-Small-Cell Lung/drug therapy, Clinical Trials, Phase III as Topic, Disease Progression, Docetaxel/therapeutic use, Female, Humans, Lung Neoplasms/drug therapy, Male, Middle Aged, Mutation, Neoplasm Staging, Proto-Oncogene Proteins p21(ras)/genetics",

author = "Jacob Aptekar and Rahul Jain and Beata Korytowsky and Afrah Shafquat and Jacob Hendershot and Aniketh Talwai and Yahav Itzkovich and Padda, {Sukhmani K.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = jul,

doi = "10.1016/j.lungcan.2024.107854",

language = "English",

volume = "193",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel

T2 - Pooled data analysis

AU - Aptekar, Jacob

AU - Jain, Rahul

AU - Korytowsky, Beata

AU - Shafquat, Afrah

AU - Hendershot, Jacob

AU - Talwai, Aniketh

AU - Itzkovich, Yahav

AU - Padda, Sukhmani K.

PY - 2024/7

Y1 - 2024/7

N2 - OBJECTIVES: Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials.MATERIALS AND METHODS: Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status.RESULTS: A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively.CONCLUSION: These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.

AB - OBJECTIVES: Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials.MATERIALS AND METHODS: Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status.RESULTS: A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively.CONCLUSION: These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Brain Neoplasms/secondary

KW - Carcinoma, Non-Small-Cell Lung/drug therapy

KW - Clinical Trials, Phase III as Topic

KW - Disease Progression

KW - Docetaxel/therapeutic use

KW - Female

KW - Humans

KW - Lung Neoplasms/drug therapy

KW - Male

KW - Middle Aged

KW - Mutation

KW - Neoplasm Staging

KW - Proto-Oncogene Proteins p21(ras)/genetics

UR - http://www.scopus.com/inward/record.url?scp=85196706851&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2024.107854

DO - 10.1016/j.lungcan.2024.107854

M3 - Article

C2 - 38917687

AN - SCOPUS:85196706851

SN - 0169-5002

VL - 193

JO - Lung Cancer

JF - Lung Cancer

M1 - 107854

ER -

Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis

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UN SDGs

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Researchers from Fox Chase Cancer Center Report New Studies and Findings in the Area of Non-Small Cell Lung Cancer (Brain Metastases In Clinical Trial Participants With kras -mutated Advanced Non-small Cell Lung Cancer Receiving ...)

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Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

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Researchers from Fox Chase Cancer Center Report New Studies and Findings in the Area of Non-Small Cell Lung Cancer (Brain Metastases In Clinical Trial Participants With kras -mutated Advanced Non-small Cell Lung Cancer Receiving ...)

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