LATE BREAKING ABSTRACT: Results from two Phase 3 randomized trials of enobosarm, selective androgen receptor modulator (SARM), for the prevention and treatment of muscle wasting in NSCLC
Speaker LBA: J. Crawford (USA)
Background: Cancer induced muscle wasting begins early in the course of malignancy. Greater than 50% of NSCLC patients have muscle wasting at diagnosis, increasing to 80% prior to death. Muscle wasting is a selective and progressive cancer related symptom that is a consequence of a reduced rate of anabolic activity and increased catabolic activity.
Enobosarm is a first in class nonsteroidal oral SARM. We report herein the top line results for two Phase 3 clinical trials, POWER1(P1) and POWER2(P2), that were conducted in patients for the prevention and treatment of muscle wasting in patients with advanced NSCLC.
Materials and Methods: Six hundred forty-one patients, with Stage III or IV NSCLC, were randomized into one of two trials at initiation of first-line chemotherapy, platinum + taxane or platinum + non-taxane. Patients received either enobosarm 3 mg or placebo for 5 months. Patients were males and postmenopausal females ≥30y, and ECOG ≤1. Coprimary endpoints (Day 84) are physical function response assessed by stair climb power (SCP) and lean body mass (LBM) as measured by DXA.
Results: Enobosarm 3mg demonstrated significant effects on LBM, with a higher percentage of responders (maintained or increased LBM) at days 84 and 147 in both trials (see table). Further, in the pre-specified secondary continuous variable analyses, enobosarm had a significant effect on LBM at both times in both trials (p=0.0003 and
You got cut off (Yahoo mb hates the less than sign).
Here is the rest:
..."less than 0.0001 in P1 at days 84 and 147: p=0.0227 and 0.0036 in P2).
% Responders in POWER1 (N=321) % Responders in POWER2 (N=320)
Day 84 Day 147 Day 84 Day 147
Enobosarm 41.9% 35.0% 46.5% 40.9%
Placebo 30.4% 23.5% 37.9% 27.9%
p value 0.036 0.026 0.113 0.013
No differences in the percentage of SCP responders (≥ 10% increase in SCP) were observed between enobosarm and placebo patients in both studies (p less than 0.2). However, a 12.5% difference (statistically significant and clinically meaningful) in SCP (change from baseline) was observed between enobosarm and placebo patients in P1, while neither a statistically significant nor clinically meaningful difference in SCP was observed in P2. In general, LBM responders had greater increases in SCP and survived longer (landmark analysis) regardless of treatment. The incidence of adverse events was similar between enobosarm and placebo subjects in both trials.
Conclusions: Overall, enobosarm 3mg was safe and well tolerated. Enobosarm had an unambiguous effect on muscle that may translate into improvement in physical function and survival in NSCLC patients.
A) SARMs take time to work. 3 months to show delta between SARM & PBO is too short. Duration likely selected given limited tox.
B) The choice of chemo matters. Taxanes seemed to result in few LBM responses. Notready to call non-taxanes "better", but use of a SARM should be evaluated mechanistically with chemo background.
C) Prior to these studies, SCP has yet to be validated clinical relevant endpoint. These studies are a step back on progress to advance such an objective.
D) Prior to these studies, LBM has grown as a clinical relevant endpoint and a surogate endpoint. These studies support such an objective, but more research is required.
i was waiting to see the final topline data for a while; well its statistically significant is the main thing
so it looks like they are having 12% difference in responders vs placebo which is not as high as you would expect for an anabolic agent maybe if they were healthier it would be 25% or higher
there are posts on bodybuilding forums where people are bragging about the gains they get from the generic enobosarm ie ostarine...so i would feel the lbm response rate would be very high and allows a gain of 3-5 lbs for the healthy weight lifters
scp is pretty terrible in terms of showing a strength benefit they should have done leg press or some other physical weighted exercise where it would be more black and white
the full survival data for the survival safety should be very conclusive that shows mOS benefit
its already known although i cant find this on their site they will release it on monday
i think we will be waiting awhile to get a say on approval since they arent filing the nda until q1 2014