Ariad 26113 for ROS1 patients resistant to crizotinib - 1245468

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mateodega
Ariad 26113 for ROS1 patients resistant to crizotinib - 1245468

Hello,

Not long ago I posted a very upbeat message of hope to the lung cancer community. My sister, a ROS1 positive nsclc patient, had had a seemingly miraculous response to crizotinib: after two cycles she was nearly her old self again and we were ecstatic. At the time, I did express concern about resistance, but many respondents encouraged me to remain optimistic.

My sister suddenly became symptomatic again two weeks ago. Her doctor concluded that crizotinib was no longer effective and Sara began a two-week "wash out" period necessary to transition to the next drug, ARIAD 26113. We were told that she will be her doctor's first ROS1 patient to try the drug.

So, my question is this: does anyone know of other ROS1 patients who have become resistant to crizotinib and who are now trying ariad 26113? If so, how long have you been on it and how is it going? What are the side effects? Any insights will be deeply appreciated.

Thank you,

Mateo

certain spring
Reply To: Ariad 26113 for ROS1 patients resistant to crizotinib

How dismaying to hear of your sister's sudden onset of symptoms after such a good result.
In case it helps, there was some discussion about Ariad 26113 on GRACE back in March, with a comment from Dr West:
http://cancergrace.org/lung/topic/acquired-resistance-to-egfr-tki/page/3...
There's also a thread about the trial on Inspire - but I don't think these are ROS patients, rather patients with the ALK rearrangement. The most recent post is from a lady who says she isn't getting any significant side effects after two months on the trial:
https://www.inspire.com/groups/lung-cancer-survivors/discussion/are-you-...
Someone who will undoubtedly know about this from a patient's perspective is Craig from PA, if he is around.

Dr West
Reply To: Ariad 26113 for ROS1 patients resistant to crizotinib

Mateo,

I'm very sorry to hear of your sister's recent worsening.

The ROS1 story is so new that it is just being written. I think many, perhaps most of the people with a ROS1 rearrangement who have started on crizotinib (XALKORI) remain on it. I wish I could offer some insight, but your sister could possibly be the very first patient with a ROS1 rearrangement who is started on the ARIAD drug. I don't know that, but the number of known ROS1-positive patients out in the world is still very limited, and I think the same can be said for people with lung cancer who have been on ARIAD 26113. The number of ROS1 patients on ARIAD 26113 is likely to be able to be counted on the fingers of one hand...

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

certain spring
Reply To: Ariad 26113 for ROS1 patients resistant to crizotinib

Just giving this a bump as I see Craig is out and about on the site and will probably have something to say about this.

craig
craig's picture
Reply To: Ariad 26113 for ROS1 patients resistant to crizotinib

(certain spring -- Thank you for mentioning this discussion in another I was following. I wasn't checking this category for new discussions.)

Mateo (mateodega),

I hope you'll forgive me for reposting my reply from elsewhere, but it might be useful for others here who haven't seen that and are following ROS1 developments. As you know, I'm very sad to hear that the good results were followed by bad news, and I am hopeful about the next drug she'll try (which I'll be trying, too, when crizotinib gives out for me).

It is shocking that the dramatic benefit had such a short duration. I have to imagine that a good portion of her cancer had something different or additional, maybe just a Xalkori-resistant variant of ROS1. I hope her medical team can identify whatever it was that was resistant.

I'll be hopeful that Ariad AP26113 has a good chance of working, at least if the resistance is not due to a totally different kind of cancer or mutation. As you've seen in the pre-clinical research for AP26113, it's really good at controlling most known ALK variants:
http://ariad.com/pdf/AP26113_AACR_2010_Zhangetal.pdf

And since the shape of the ALK mutation is similar to the ROS1 mutation, but on a different chromosome, my guess is that there's a good chance AP26113 could control most ROS1 variants (at least most that could have appeared after only 2-3 months on Xalkori). I think the very few ALKies who have reported trying AP26113 in online discussion forums all seemed to be helped by it. I'm looking forward to trying AP26113 when I develop resistance.

I'm so very sorry that your sister had such an unfairly short benefit. My thoughts are with her as she transitions to trying AP26113, and with her medical team as they try to pinpoint why Xalkori wasn't enough for long.

Best hopes,

Craig

_________________________________
Stage 4 ROS1+ [mucinous BAC] adenocarcinoma NSCLC since 2011
Xalkori (crizotinib) 5 yrs
Alimta (pemetrexed) + carboplatin (mere months)
TPX-0005 (repotrectinib) TBD (1+ years as of Fall 2018)