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

PloS One
Katsuyuki HottaKatsuyuki Kiura

Abstract

In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly 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. 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 cytotoxic 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<0.01). A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%). The odds ratio for overall response was higher in trials with molecularly selected patients than in all-c...Continue Reading

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Citations

Jul 14, 2017·British Journal of Cancer·Tristan A Barnes, Eitan Amir
Jul 11, 2018·International Journal of Technology Assessment in Health Care·Karla Hernandez-VillafuerteNicholas Latimer
Mar 9, 2019·International Journal of Clinical Oncology·Satoru SenooKatsuyuki Kiura
Dec 7, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Giovanni RossiFrancesco Grossi
Jun 16, 2021·Value in Health Regional Issues·Yesenia OrtizEsteban Hernández

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