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)


Nexavar (Sorafenib) Shows Survival Benefit for EGFR Mutation-Positive NSCLC but Fails in Broader Population
Howard (Jack) West, MD

It has been a long time since we've talked about Nexavar (sorafenib), an oral anti-angiogenic targeted therapy that works as a "multi-kinase inhibitor"  and is FDA approved in some other cancers such as renal cell and liver cancer.  In lung cancer, some small, early research done years ago revealed that it has activity in at least a minority of patients with advanced NSCLC.  Since then, it showed no benefit in combination with first line chemo in the ESCAPE trial, showed some promise in KRAS mutation-positive advanced NSCLC (though later work failed to validate this observation), and again showed activity as a single agent for at least some patients with previously treated advanced NSCLC.  But at the annual conference of the European Society for Medical Oncology (ESMO), just recently held in Vienna, the results of a larger randomized MISSION trial of Nexavar with supportive care vs. placebo with supportive care as third or fourth line treatment for advanced NSCLC revealed no benefit for overall survival.  However, the subset of patients with an EGFR mutation demonstrated a survival benefit from Nexavar.

Results from the randomized trial are summarized here. Briefly, 703 patients with previously treated advanced NSCLC were randomized to best supportive care along with either the standard dose of Nexavar at 400 mg by mouth twice daily, or placebo on the same schedule.  Though the patients receiving Nexavar had a significantly better response rate  (P < 0.001), disease control rate (significant tumor shrinkage or stable disease)  (P < 0.001), and progression-free survival ( (P < 0.0001), there was no improvement in the primary endpoint of overall survival.

However, almost exactly half of the patients enrolled on the MISSION trial had EGFR and KRAS mutation data available from tumor tissue or serum samples. Among that group, 26% of patients had an EGFR mutation, and a KRAS mutation was seen in 20%, and the frequency of these mutations was balanced between the two arms.

While this analysis showed no difference in outcomes with Nexavar in the patients with a KRAS mutation, the results were very different among the 89 patients with an EGFR mutation.  In that group, there was an approximately four-fold higher probability of patients on Nexavar not progressing at a given time point (HR 0.27; P <0.001), and an approximately two-fold higher probability of them being alive at a given time point (HR 0.48; P = 0.002); the median overall survival was than doubled in the Nexavar arm (423 days vs. 197 days). 

These results are definitely favorable,  but it's important to note that the positive results are still in just a few dozen patients -- a definitive answer will require a prospective trial of only EGFR mutation-positive patients.  Even if that trial is done, results won't be available for years. In the meantime, with Nexavar being commercially available already, I suspect I won't be the only oncologist interested in trying to obtain it for my EGFR mutation-positive patients. 

What do you think of these results?  I suspect that most EGFR mutation-positive patients with an EGFR mutation-positive NSCLC would want to try to obtain Nexavar, but if it isn't covered by an insurer, would it be worth paying several thousand dollars per month for?  For those without an EGFR mutation, are these results convincing enough that there isn't a real benefit, or does the improvement in response rate and progression-free survival count for much even if survival isn't improved?

Next Previous link

Previous PostNext Post

Related Content

Lung Cancer OncTalk 2023
At our live event, Lung Cancer OncTalk 2023, Dr. Jeff Yang, discusses different surgical procedures used to treat early-stage lung cancer and different approaches to removing cancerous tissue from the lung. 
Lung Cancer OncTalk 2023
At our live event, Lung Cancer OncTalk 2023, Dr. Millie Das, discusses different Studies and Trials for NSCLC. Dr. Das specializes in the treatment of thoracic malignancies. She sees and treats patients both at the Stanford Cancer Center and at the Palo Alto VA Hospital. She is the Chief of Oncology at the Palo Alto VA and is an active member of the VA National Lung Cancer Working Group and Lung Cancer Precision Oncology Program. Learn more about Dr. Das here.
The Importance of Early Detection 2023
Drs. Meredith McKean, Dr. Doug Micalizzi and patient advocate and lung cancer survivor, Ivy Elkins, discuss the importance of early detection and treatment across cancer types, including skin, lung, and breast. To watch the complete playlist click here.

Forum Discussions

Hi Blaze,


As much as I hate to say it, Welcome back Blaze.  It sounds like you're otherwise feeling good and enjoying life which is a wonderful place to be. ...

Waiting for my appointment with oncologist this morning. Thank you for the response. It helps. <3

It sounds like you’re thinking of this in a very appropriate way. Specifically, it sounds like the growth of the nodule is rather modest, though keep in mind that the change...

Hi and welcome to GRACE.  I'm sorry your mom is having this difficulty.  An indwelling catheter is used when the pleura space continually fills and the catheter is always there to...

Hi Oaktowngrrl,  Welcome to Grace.  I'm so sorry you're going through this.


 Finding a reputable dedicated thoracic surgeon for lung surgery might be difficult, as it is a complex and...

Recent Comments

Could you
By Maeve785 on
It sounds like you’re…
By Dr West on
Thank you Janine
By blaze100 on
Hi Blaze,


As much as I…
By JanineT GRACE … on