Darolutamide vs. Apalutamide vs. Enzalutamide

[MateoBeach]

Comparison based on matching patients from three trials. The best we have at present. If side effects are intolerable from enzalutamide or apalutamide then this should provide ammo to justify switch to Nubeqa. Especially for brain related problems.

practiceupdate.com/C/121225...

PURPOSE

No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons.

MATERIALS AND METHODS

Individual patient data from the phase III ARAMIS trial (NPLACEBO=553; NDAROLUTAMIDE=943) were selected and reweighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (NPLACEBO=401; NAPALUTAMIDE=806) and PROSPER (NPLACEBO=468; NENZALUTAMIDE=933) trials. Only baseline factors consistently reported across trials were included as matching covariates. Both indirect comparisons matched on age, prostate specific antigen level and doubling time, Eastern Cooperative Oncology Group performance status, Gleason score, and bone-sparing agent use. Darolutamide vs apalutamide also matched on prior surgery and darolutamide vs enzalutamide also matched on region. Risk differences and odds ratios were calculated for adverse events and hazard ratios for metastasis-free survival.

RESULTS

No differences in metastasis-free survival hazard ratios were found after matching in either comparison. However, fall, fracture and rash rates were statistically significantly lower in favor of darolutamide vs apalutamide. Fall, dizziness, mental impairment, fatigue and severe fatigue rates were statistically significantly lower in favor of darolutamide vs enzalutamide.

CONCLUSIONS

While metastasis-free survival did not differ across drugs in these cross-trial indirect comparisons, darolutamide showed a favorable safety and tolerability profile in prespecified adverse events vs apalutamide and enzalutamide. Consideration of these adverse events is important in clinical decision-making and treatment selection in nonmetastatic castration-resistant prostate cancer.

[Boywonder56]

Ive been on erleada for 4.5 yrs in titan trial....i had number of falls 2nd year but didnt attribute them to meds since was double blinded trial...but now since trial has been unblinded and ive been in erlead since git go....might have been considerd ...i am now getting head aches....and know that this stuff permeates blood layer in brain....have metioned to trial doc but no answere....so i started splitting dose 2 in am 2 in pm....seems to help...ive had good results and prob wont rock bought yet...thanks for info mb....always appreciated

[MateoBeach in reply to Boywonder56]

They generally won’t tell you about options when I’m a trial. They work for the trial protocol not you. So you have to make your own decision or talk to an MO outside of the trial. Sounds like you are okay for now.

[podsart]

What I had heard early on was that daralutamide also had benefits in terms of the AR mutation process, thereby forestalling resistance for a period. What happened to this assertion?

[Horse12888]

This is very good news for people like me for whom the depression brought on by ADT makes life not worth living and pushes us to the point of suicidality. Of course, these AR blockers are prescribed ON TOP OF GnRH drugs, so perhaps this isn't the boon it looks like.

[MateoBeach in reply to Horse12888]

Maybe worth a try. Other alternatives to LHRH ADT drugs include bicalutamide with dutasteride. Also Abiraterone with prednisone has been shown to reduce testosterone to castrate without needing any other ADT. Also estradiol patch added can help very much with ADT SEs including depression.

[Horse12888 in reply to MateoBeach]

I was unaware that it prescribed to men who aren't on the standard GnRH drugs. Can you send me a link to something that refutes this?

[MateoBeach in reply to Horse12888]

This one among others. ascopubs.org/doi/abs/10.120...