My husband (ALK+) had NED on crizotinib and NED on LDK378. When the cancer returned, he had PET scan while still on the LDK378. Then he went off it for 7 days for a washout period before starting X-396 clinical trial. After being on X-396 for 10 days, he was told to stop the X-396 for 10 days due to a grade 2 rash. He started X-396 again and developed a really bad cough. The cough then greatly improved about a week before his 8-week scans. The CT scan showed progression from the PET scan 9 weeks prior.
Do you think the progression is due to flare while he was off any inhibitor drug for a total of 17 days and the X-396 just didn't have time to control it before his CT scan, or do you think the X-396 actually failed? He was pulled out of the clinical trial due to progression of disease.
We are trying to get "compassionate use" granted for alectinib but they are saying it treats a similar mechanism as X-396 and they don't think it would work for him if X-396 didn't work.
He has been off trial now for a week and I am panicking because his cough is getting worse again. We need to make a decision on treatment and are considering either Alimta or the brand new RXDX-101 clinical trial (phase 1).
Reply # - November 4, 2014, 08:37 PM
I can't speculate about what
I can't speculate about what is happening here. I am skeptical about the likely benefit of giving multiple agents with remarkably overlapping mechanisms of action, compared with an approach like chemotherapy. There is even suggestive evidence that Alimta (pemetrexed) is often quite helpful for patients with an ALK rearrangement. In contrast, there is no evidence at all that trying a 3rd or 4th ALK inhibitor will have any benefit. I would be far more hopeful about trying a new angle rather than playing a slight variant of the same song, over and over and over, that the cancer has already mastered.
Good luck
-Dr. West
Reply # - November 6, 2014, 06:27 AM
Thank you for your speedy
Thank you for your speedy reply. Your answer was extremely helpful in helping us make a decision on treatment.
Have you had any patients who had success on ALK inhibitors who then went back on Alimta after progression occurred? How long did the Alimta work?
If the Alimta eventually fails to control the cancer, would retrying the same ALK inhibitors (that previously allowed NED to occur) work again?
Reply # - November 6, 2014, 06:37 AM
Hello,
Hello,
In general, although it is at times attempted, returning to previous agents on which the cancer progressed usually does not provide much if any benefit. In answer to a question (and situation) similar to yours, Dr. West, reiterating his reluctance to try another 2nd generation ALK inhibitor, stated:
"[W}henever progression is more definitively identified, the drug Taxotere (docetaxel) is one that she hasn’t yet received and still has a proven survival benefit in patients who have received prior chemotherapy. Otherwise, it’s possible, though I think unlikely, that another 2nd generation ALK inhibitor like CH5424802 (alectanib) from Chugai/Roche or AP26113 from Ariad will be effective after having received LDK378. There is also some modest but provocative results showing that people with advanced NSCLC and an ALK rearrangement may be good responders to the investigational drugs in the class of heat shock protein (HSP90) inhibitors, so perhaps it’s possible to find a trial with one of these agents." - http://cancergrace.org/topic/suspicious-small-nodule-in-left-lobe-while…
JimC
Forum moderator
Reply # - November 6, 2014, 06:09 PM
Yes, it may be possible to
Yes, it may be possible to return to an agent on which the cancer previously progressed. Every once in a while, the treatment is beneficial, though usually only very minimally and transiently.
-Dr. West