Efficacy of targeted therapies for oncogene-driven lung cancer in early single-arm versus late phase randomized clinical trials: A comparative analysis.

Details

Serval ID
serval:BIB_BFD000998B6C
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Efficacy of targeted therapies for oncogene-driven lung cancer in early single-arm versus late phase randomized clinical trials: A comparative analysis.
Journal
Cancer treatment reviews
Author(s)
Tan A.C., Tan S.H., Zhou S., Peters S., Curigliano G., Tan DSW
ISSN
1532-1967 (Electronic)
ISSN-L
0305-7372
Publication state
Published
Issued date
03/2022
Peer-reviewed
Oui
Volume
104
Pages
102354
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
There is an expanding number of approved targeted therapies for oncogene-driven lung cancer and many emerging therapies with promising efficacy data. Regulatory approvals are increasingly based on early phase trials (often single-arm phase II trials), in which the primary endpoint is objective response rate (ORR) or progression-free survival (PFS). Efficacy outcomes from early phase trials may not always correlate with those observed in later-phase randomized trials. In the precision oncology era with effective targeted therapies however, there are arguments for greater confidence in the efficacy outcomes from non-randomized single-arm trials. Nevertheless, there remain numerous challenges in understanding and interpreting efficacy outcomes for novel targeted therapies in trials that may have dose finding and safety as the primary objective and lack a standard-of-care control arm. Therefore, we sought to review the efficacy outcomes in early versus late phase clinical trials for approved targeted therapies in lung cancer - to better understand the interpretation of preliminary measures of clinical benefit. Nine pairs of early and late phase trials were identified, according to line of therapy for six targeted therapies in lung cancer (afatinib, ceritinib, crizotinib, dacomitinib, lorlatinib and osimertinib). Key efficacy outcomes, including ORR, PFS and overall survival (OS) were compared. Importantly, we found that in oncogene-driven lung cancer, early phase trial outcomes have historically been consistent with subsequent late phase trials. This suggests efficacy outcomes from early phase trials of targeted therapies in lung cancer may translate reliably to larger randomized trials. This has many potential implications for drug development in lung cancer, with regards to regulatory approvals and the design and conduct of clinical trials.
Keywords
Carcinoma, Non-Small-Cell Lung/drug therapy, Humans, Lung Neoplasms/drug therapy, Lung Neoplasms/genetics, Oncogenes, Precision Medicine, Protein Kinase Inhibitors/therapeutic use, Randomized Controlled Trials as Topic, Drug approval, Early phase trials, Non-small cell lung cancer, Randomized controlled trials, Targeted therapy
Pubmed
Web of science
Create date
12/02/2022 15:33
Last modification date
11/11/2022 7:39
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