TY - JOUR
T1 - Activity of 129 single-agent drugs in 228 phase i and II clinical trials in multiple myeloma
AU - Kortuem, K. Martin
AU - Zidich, Kaitlyn
AU - Schuster, Steven R.
AU - Khan, Meaghan L.
AU - Jimenez-Zepeda, Victor H.
AU - Mikhael, Joseph R.
AU - Fonseca, Rafael
AU - Stewart, A. Keith
PY - 2014/8
Y1 - 2014/8
N2 - Background More than 400 preclinical studies report > 1 compound as cytotoxic to multiple myeloma (MM) cells; however, few of these agents became relevant in the clinic. Thus, the utility of such assays in predicting future clinical value is debatable. Patients and Methods We examined the application of early-phase trial experiences to predict future clinical adoption. We identified 129 drugs explored as single agents in 228 trials involving 7421 patients between 1961 and 2013. Results All drugs in common use in MM (melphalan, dexamethasone, prednisone, cyclophosphamide, bendamustine, thalidomide, lenalidomide, pomalidomide, bortezomib, carfilzomib, and doxorubicin) demonstrated a best reported response rate of > 22%. Older agents, including teniposide, fotemustine, paclitaxel, and interferon, also appear active by this criterion; however, if mean response rates from all reported trials for an agent are considered, then only drugs with a mean response rate of 15% partial response are in clinical use. Conclusion Our analysis suggests that thresholds of 20% for best or 15% for mean response are highly predictive of future clinical success. Below these thresholds, no drug has yet reached regulatory approval or widespread use in the clinic. Thus, this benchmark provides 1 element of the framework for guiding choice of drugs for late-stage clinical testing.
AB - Background More than 400 preclinical studies report > 1 compound as cytotoxic to multiple myeloma (MM) cells; however, few of these agents became relevant in the clinic. Thus, the utility of such assays in predicting future clinical value is debatable. Patients and Methods We examined the application of early-phase trial experiences to predict future clinical adoption. We identified 129 drugs explored as single agents in 228 trials involving 7421 patients between 1961 and 2013. Results All drugs in common use in MM (melphalan, dexamethasone, prednisone, cyclophosphamide, bendamustine, thalidomide, lenalidomide, pomalidomide, bortezomib, carfilzomib, and doxorubicin) demonstrated a best reported response rate of > 22%. Older agents, including teniposide, fotemustine, paclitaxel, and interferon, also appear active by this criterion; however, if mean response rates from all reported trials for an agent are considered, then only drugs with a mean response rate of 15% partial response are in clinical use. Conclusion Our analysis suggests that thresholds of 20% for best or 15% for mean response are highly predictive of future clinical success. Below these thresholds, no drug has yet reached regulatory approval or widespread use in the clinic. Thus, this benchmark provides 1 element of the framework for guiding choice of drugs for late-stage clinical testing.
KW - Drugs
KW - Early clinical trials
KW - Multiple myeloma
KW - Phase 1
KW - Single-agent activity
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U2 - 10.1016/j.clml.2013.12.015
DO - 10.1016/j.clml.2013.12.015
M3 - Article
C2 - 24565465
AN - SCOPUS:84904611561
SN - 2152-2650
VL - 14
SP - 284-290.e5
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -