Hi All,
Anyone here has had experience with Ipilimumab ( Yervoy) along with Nivolumab ( Opdivo)? I know the earlier study showed severe toxicity but I heard that later on, when the yervoy dose was reduced from 3mg/kg to 1mg/kg, the safety profile became much better and the combination became much better tolerated. Stephen, Any thought on efficacy or on whether it is worth trying in GBM? Many thanks for the help.
Noha
Anyone here has had experience with Ipilimumab ( Yervoy) along with Nivolumab ( Opdivo)? I know the earlier study showed severe toxicity but I heard that later on, when the yervoy dose was reduced from 3mg/kg to 1mg/kg, the safety profile became much better and the combination became much better tolerated. Stephen, Any thought on efficacy or on whether it is worth trying in GBM? Many thanks for the help.
Noha
The latest news on this is from the 2016 ASCO conference that just ended.
ReplyDeletehttp://abstract.asco.org/176/AbstView_176_163804.html
http://global.onclive.com/conference-coverage/asco-2016/nivolumab-effective-in-early-stage-study-for-glioblastoma
Yes, the lower dose of ipilimumab (Yervoy) was much more tolerable, but still the survival statistics of combined nivolumab + ipi was no better (in fact slightly worse) than nivolumab alone. Overall survival at 12 months was 35% with nivolumab + lower dose ipi, versus 40% with nivolumab alone. This is not a major difference, but it doesn't appear that adding ipi is improving the effectiveness of nivolumab in this trial.
Median survival from trial start reported here is mediocre, about the same as would be expected with other standard treatments, like temozolomide or Avastin + CCNU.
One out of 10 patients had a partial tumor response with nivolumab alone and there was a 50% stabiliziation rate. In the nivo + ipi (lower dose) arms there were no responses, with a stabilization rate of 50%.
I expect these checkpoint inhibitors will be much more effective when combined with vaccines, as they are starting to do in trials (such as one currently recruiting at Duke). The experience in other cancers is that the PD-inhibitors are more likely to be effective in hypermutated recurrent tumors. Hypermutated recurrence might be expected in ~20 or 25% of GBM cases.
The data so far shows (at least temporary) disease stabilization in about half the patients treated, and one response out of 40 patients (all 3 cohorts combined). The data so far does not suggest adding ipilimumab (at either dose) improves results over nivolumab alone.
Thanks Stephen, I came across this: http://neuro-oncology.oxfordjournals.org/content/16/suppl_5/v163.5.short?rss=1
ReplyDeleteI also spoke to a NO who mentioned that the results shared during ASCO2016 for ipilimumab in non small lung cancer was very promising. Response to Opdivo alone was 11%. When ipilimumab was added to Opdivo at a reduced dose of 1mg/kg every 6 weeks rather than 3mg/kg every 3 weeks, the toxicity became much less and manageable and the response rate jumped to almost 40%. I am waiting on the publication and will share when I receive it.
Would you happen to know if the brain swelling seen in the initial stages of the Opdivo + ipilimumab trial was related to Opdivo or Ipilimumab?
Thanks very much
Noha
I'm glad to hear that the combination worked so well in lung cancer. Unfortunately adding ipi (any dose) to nivolumab has not improved survival or response rates in GBM in the preliminary results available, compared with nivolumab alone.
DeleteI don't know all the details, but word-of-mouth has it that the ipilimumab was deemed too toxic, and that trial has moved into phase 3 with only nivolumab (Opdivo).
I collected the conversations from the old cancer compass thread into this blog post:
http://btcocktails.blogspot.ca/2015/09/cancer-compass-review-pd-1-inhibitors.html