Magnitude of the benefit of progression-free survival as a potential surrogate marker in phase 3 trials assessing targeted agents in molecularly selected patients with advanced non-small cell lung cancer: Systematic review

Katsuyuki Hotta, Yuka Kato, Natasha Leighl, Nagio Takigawa, Rabab Mohamed Gaafar, Hiroe Kayatani, Taizo Hirata, Kadoaki Ohashi, Toshio Kubo, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

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Abstract

Background: In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecu-larly selected patients with advanced non-small cell lung cancer (NSCLC), overall survival (OS) as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. Methods and Findings: We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotox-ic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design). Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs. 1.04), the former exhibited greater progression-free survival-hazard ratios (PFS-HR) (mean, 0.40 vs. 1.01; P

Original languageEnglish
Article numbere0121211
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 16 2015

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systematic review
lung neoplasms
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Disease-Free Survival
Hazards
Biomarkers
Cells
Chemotherapy
tyrosine
phosphotransferases (kinases)
Survival
cells
endpoints
ROC Curve
drug therapy
Drug Therapy
Therapeutics
methodology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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abstract = "Background: In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecu-larly selected patients with advanced non-small cell lung cancer (NSCLC), overall survival (OS) as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. Methods and Findings: We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotox-ic chemotherapy (eight trials were performed in molecularly selected patients and ten using an {"}all-comer{"} design). Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs. 1.04), the former exhibited greater progression-free survival-hazard ratios (PFS-HR) (mean, 0.40 vs. 1.01; P",
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AU - Kato, Yuka

AU - Leighl, Natasha

AU - Takigawa, Nagio

AU - Gaafar, Rabab Mohamed

AU - Kayatani, Hiroe

AU - Hirata, Taizo

AU - Ohashi, Kadoaki

AU - Kubo, Toshio

AU - Tabata, Masahiro

AU - Tanimoto, Mitsune

AU - Kiura, Katsuyuki

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