FACULTY COMMENTS
DR RICHARDSON: ECOG-E4A03 is a landmark trial, which evaluated
the activity and toxicity of high-dose dexamethasone versus
lower-dose dexamethasone when combined with lenalidomide
and how this affects patient outcome, including overall survival.
The most powerful message from this study was that the oneyear Kaplan-Meier overall survival estimate is striking, with a 96.5 percent survival for lenalidomide and low-dose dexamethasone, which is probably the best seen in any Phase III trial of this size to date. In contrast, the high-dose arm did less well, with an 88 percent chance of one-year survival. Somewhat surprising was that the response rates were significantly higher for the high-dose dexamethasone arm, which ultimately performed poorer in terms of survival. Having said that, the overall response rates for both arms are very respectable, and I believe the good news for patients is that we’re dealing with a new combination — lenalidomide and low-dose dex — which is associated with a very encouraging survival at one year, coupled with the convenience of an oral regimen. Unfortunately, high-dose dex contributes excess toxicity to this combination, and therefore, low-dose dex should generally be used. However, the quality of responses on low-dose dexamethasone was lower, and so this may indicate that we need a third drug, or even more, to achieve a better response and to potentially further enhance clinical benefit.
DR JAKUBOWIAK: Mostly, we eliminated the high toxicity levels
with high-dose dex, which was the primary cause of early
mortality, especially in older patients. It is important not to
lose any patient from toxicity, but the switch to low-dose dex
may haunt us. The response rate for Rd was clearly inferior
compared to other active regimens, including PAD, VDD, RVD
and VTD, which are in the 90 percent range. The response rate
for Rd is approximately 70 percent. Some predict these patients
will relapse earlier and have a shorter survival.
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