My friend who is ALK positive has been on Alectinib for about 1 year and has had stable disease up until scans this past week which showed 2 new lesions. One 2.4 cm and one 1 cm located behind the renal artery. These are new since last study 9 weeks ago. All the old lesions including brain mets remained stable. What are the third generation TKI' s out there for Alk?
Sat, 08/22/2015 - 12:08
I'm sorry your friend is going through this. You're a good friend to help look for next options. I've asked an onc to reply. In the meantime could you let us know what other treatment your friend has had?
There aren't any available 3rd gen ALK tki drugs. You may want to look at http://clinicaltrials.gov/ for trial options.
Sat, 08/22/2015 - 15:58
The only other med she has been on is xalkori. She started it at full dose but got so sick she almost died had to stop it restarted it at half dose after 6 weeks and stayed on that for a couple of months till she had increase in brain mets and we were lucky enough to get into the Alectinib study. She had radiation to her spine and hip mets last year also. She had initial regression of all tutors when she first started Alectinib and remained stable for a year but now new tutors. The old rumors remained stable.
Mon, 08/24/2015 - 13:55
Mon, 08/24/2015 - 15:43
Thank you I have watched all of these last year. I was hoping to hear from one of the oncologist. Will they respond?
Mon, 08/24/2015 - 20:48
Yes, I'll make sure that happens tonight or tomorrow. Sorry for the wait, we're trying to give our oncologists more time to respond before calling out the big guns (aka West). We do understand you're asking questions that need answers now and why we're here. Thanks for the heads up.
Mon, 08/24/2015 - 21:27
Unfortunately, there's no 3rd generation ALK inhibitors with any established response shown in patients who have progressed on a 2nd generation ALK inhibitor. There are multiple 2nd generation ALK inhibitors, but just about every trial of these has excluded patients who have already been on another 2nd generation ALK inhibitor.
Because of this, we really don't know of any ALK-directed therapy for patients after their cancer progresses on a 2nd generation ALK inhibitor. It's reasonable to try another ALK inhibitor, but very often this will not be very helpful, and I tend to favor conventional chemotherapy at that point instead.
Tue, 08/25/2015 - 05:47
Thank you Dr. West. I desperately wanted a different answer but after researching all the sites felt that was the answer.
Sun, 08/30/2015 - 07:25
Janine/Dr West,I had thought (and hoped) that Pfizers PF06463922 was a third generation inhibitor, and was promising and available in patient clinical trials in some hospitals? Thank you, Alicia.
Sun, 08/30/2015 - 10:07
It is a third-generation ALK inhibitor, and is available in a phase I/phase II trial, listed at clinicaltrials.gov here). Dr. West's comment was that there aren't any such inhibitors "with any established response shown in patients who have progressed on a 2nd generation ALK inhibitor." Although it may prove to be effective in this context, it's just to early to say that about this drug.
Fri, 01/15/2016 - 14:31
Well Robin failed on the third generation PF -3922 study. Although it may have slowed down progression some. The last 2 studies she had new nodes each time and the previous new nodes had grown by about 1cm. On the PF-3922 she haw growth of about 0.7 cm on the 5 pre existing nodes but had many new small nodes. But there was no progression in her brain. We are now on the Opdivo/ Zykadia trial. Have only been on it around 10 days. She was on no Meds x 10 days and her cancer pain got very bad. Previously after being back on a TKI about 3 days her pain quickly returned to baseline. That has not happened this time and her many side effects she had with Xalkori are back severely. Orthostatic hypotension, tinnitus , photosensitivy, balance if off, severe fatigue, and nausea. We moved her time to take Zykadia to night which has helped to lessen the nausea some. I am very worried this means the Meds aren't working. Our other choice at this point is standard chemo. She was rebiopsied in November and has no new mutations. ALK only. What are the stats on standard chemo with ALK? What percentage responds and what is the average amount of time they respond?
Sat, 01/16/2016 - 08:24
I'm sorry that the PF-3922 trial was not very effective for Robin. As far as the current trial, the problem with immunotherapies such as Opdivo is that unlike chemotherapy or targeted therapies they can take some time to show efficacy. Although you would hope that Zykadia would help faster than that, ten days is a short period (although I understand it can seem very long when symptoms and toxicities are so tough to manage) and certainly much too soon to judge the efficacy of either drug, especially Opdivo.
Patients with ALK rearrangements tend to respond well to chemotherapy, and there is evidence that Alimta (pemetrexed) can be especially effective. Dr. West discussed this topic here.
At this point, it is a question of whether to wait to see if Opdivo will be effective, or seek a possibly quicker response from a chemotherapy agent such as Alimta.
Mon, 01/18/2016 - 13:46
1. The response rates to standard chemotherapy for ALK+ lung cancer tend to be quite good, much better than most lung cancer.
2. In the situation described above, I'd consider doing stereotactic radiation (SBXRT) to the 1-2 new lesions and stay on the alectinib. SBXRT is 3 - 5 days of high-dose focused radiation. Of course, it all depends where the lesions are, and other logistical issues. At our center, we give 5 days of SBXRT, starting on Monday and finishing on Friday, to multiple lesions at once.