Article and Video CATEGORIES

Cancer Journey

Search By

Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

ARQ197: Encouraging Results from ASCO 2010

Please Note: New Treatments Have Emerged Since this Original Post
Author
Howard (Jack) West, MD

Continuing with the webinar discussion I had with Dr. Pennell, here is a summary I did of a randomized phase II trial of the novel agent ARQ-197 combined with the EGFR inhibitor Tarceva (erlotinib): ==================================== Dr. West: We're going to shift gears and move into the metastatic setting, and this is a new agent called ARQ197 that is orally available, which was tested in combination with erlotinib(Tarceva) compared with Tarceva alone. And this was actually in the patients who had received one or more prior lines of chemo and could not have received prior Tarceva or another EGFR inhibitor, directly comparing these two groups that randomized one-to-one. Also, patients who had been assigned to placebo could actually go on the combination at the time of progression, and we did get some interesting information from that. schiller-arq197-schema (click on image to enlarge)

The study enrolled very quickly: it was a randomized Phase II trial, and I'll show you the numbers very shortly. My center was one that was planning to be involved, but it actually enrolled so quickly at a few centers that we didn't even get the chance. So what is this ARQ197? It's a MET inhibitor, and MET stands for mesenchymal-epithelial transition factor, and this is involved in the cascades of EGFR and KRAS and others. met-mechanism-of-action And it's actually one of the potential mechanisms for resistance to EGFR-inhibition and in itself is associated with cell proliferation, motility, migration, angiogenesis, this transition from epithelial to mesenchymal that is associated with resistance to EGFR-inhibitors and promotes invasion and metastasis and it's associated with worse outcomes when it's over-expressed in patients with lung cancer tumors. The study involved 167 patients randomized between the two arms and showed an improvement in progression-free survival, which was the primary endpoint of the study. schiller-arq-197-pfs It was statistically significant and a really clear difference between the two arms as you can see that its hazard ratio of 0.81 corresponds to a 19% improvement, although it was especially concentrated at the median point which is here at 0.5, you could see a very significant difference. The overall survival was in favor of the combination, though it was not statistically significant and that's shown here, a difference of about seven weeks or so. schiller-arq-197-os The study also included a breakdown looking at a few different variables, and one was by histology. When they looked at patients with non-squamous tumors, which were the majority -- about two thirds -- they found that overall survival actually was significantly better with ARQ197. schiller-arq-197-pfs-and-os-in-non-squamous This was unplanned, but nowadays we know that histology can be extremely relevant and the differences are even more robust if we concentrated the evaluation at patients with non-squamous histology. They also looked at a few molecular variables, and what was interesting to see was that there was even more of a pronounced benefit in the patients who were EGFR wild type who we generally think of as not getting as profound a benefit with EGFR-inhibitors like Tarceva. schiller-arq-197efficacy-by-subgroups But here there was a really differential effect, admittedly in not incredibly large numbers, but it was still nearly a hundred patients. And also in patients with KRAS mutations, again small, small numbers, but this is a group of patients for whom we have not seen, had very difficult time making gains. Certainly, if this holds up in larger studies, it would represent a major benefit to be able to find something that could actually improve outcomes for the patients who we haven't been able to serve extremely well with Tarceva alone. What's also instructive is to see an improvement in some patients who were assigned to Tarceva alone and then crossed over to the combination, because there were actually two out of 23 evaluable who actually demonstrated significant tumor shrinkage and another nine who had stable disease. So you actually saw some improvement in people who had already been exposed to the same EGFR-inhibitor without the novel agent. This is going to be moving forward in a larger study that I'm very much hoping to be involved with, and the final design of that is still in the works at this point. Dr. Pennell: Hopefully, that one will not accrue so quickly that you won't be able to participate. Dr. West: Yeah, right -- well, it will be a larger study. Overall, I would say this is certainly an encouraging avenue. I'd welcome your thoughts, Nate. Dr. Pennell: I completely agree. I think this is an exciting avenue. We tend to get caught up with these targeted drugs, looking at the relatively small subpopulation of patients who have really the driving molecular changes like an EGFR mutation or the ALK translocation. We have to remember that the vast majority of patients with non-small cell lung cancer don't have a single genetic change that's driving it, but rather a number of different pathways that are active in their cancer cells. And MET is a pathways that is one of the highest of all the tyrosine kinases, and the activities of the MET receptor are among the most important pathways activated in lung cancer -- at least in lung cancer cell lines -- and probably that's true in actual lung cancer as well. It's probably not a single molecular change causing this, and so inhibition of MET by itself is unlikely to have a whole lot of benefit. But in combination with other drugs such as EGFR inhibitors, I think this is a very promising approach, especially for people who don't have an EGFR mutation. The KRAS data is intriguing. We'd caution everyone that there were only 15 patients with KRAS mutation for this analysis, so it's very hard to say comparing five patients to 10 patients is meaningful, but certainly, it should be looked at in larger studies of similar benefit. So I'm excited, I agree.

Next Previous link

Previous PostNext Post

Related Content

Image
Terapias Dirigidas de Cancer de Pulmón 2024
Video
La Dra. Estelamari Rodríguez presenta información básica sobre el NSCLC EGFR+ y analiza la importancia de las pruebas de biomarcadores en el cáncer de pulmón y ofrece una descripción general de las opciones de tratamiento para la enfermedad EGFR+.  Para ver la playlist completa, de click aquí.        
Image
2024-25 patient perspectives header
Article
Tell your story and help us help others! Apply online now for this paid opportunity. This program gives a voice to those who have experience in participating in a clinical trial for a cancer diagnosis. Your voice helps to educate and advocate for others who are in or who may be considering a clinical trial.  We want to hear from you!
Image
HPV Advances
Video
In this video series, Dr. Paul Romesser discusses recent advances in HPV related cancers, including treatment options, vaccination recommendations and patient perspectives.   To watch the full playlist click here.  

Forum Discussions

Radiation + Brain Operation has just been discarded due to high risk. They will double Tagrisso dosis and then wait to see if it works, then try traditional Chemo. I would...

Hi and welcome to GRACE.  I'm sorry to know you are entering a new stage.  I'm not about to comment just now but wanted to let you know I see your...

Edit to say, we can't give advice but we can comment with views and facts.  :)

 

My first thought is to ask if she has been seen at a large...

Hi Barbro, Welcome to GRACE. I'm sorry you're worrying about this. We aren't able to give feedback on scan reports. Interpreting scan reports in this setting is not only unethical but...

Hi Miranda, I hope I can put your mind at ease. The reasons for your symptoms are numerous and a pancoast tumor is close the bottom of that list.  A lot...

Hello CRT, Welcome to GRACE.  I'm so sorry your husband's cancer is figuring out a work around tagrisso.  I'm sorry his onc hasn't been more communicative.  It's pretty standard to stay...

Thank you for your quick reply! What you mention about hospice makes sense.

And thank you for the link regarding other opinions.

My husband recently took a Guardant blood test but...

Recent Comments

JOIN THE CONVERSATION
My first thought is to ask…
By JanineT GRACE … on
Hi CRT, I wanted to share…
By JanineT GRACE … on
Hi and welcome to GRACE.  I…
By JanineT GRACE … on
Update
By APT_CL on