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)

 

FLEX Trial of Chemo +/- Erbitux Shows Survival Benefit
Author
Howard (Jack) West, MD

Merck KgAA, the company developing cetuximab/Erbitux, the monoclonal antibody against EGFR, reviewed here) outside of the US, has announced that their pivotal FLEX trial (for First-Line Trial for patients with EGFR-Expressing Advanced NSCLC) is positive, demonstrating a signficant improvement in overall survival, as indicated here. I mentioned it as an important study to define any role for Erbitux in NSCLC, especially since a recent randomized trial I described in a prior post was reportedly negative.

The press release includes no details, just a glimpse of the trial, with a progress report last presented at ASCO 2006 (abstract here). This is a European phase III randomized trial with just over 1000 patients with previously untreated advanced NSCLC that had to have EGFR protein expression by immunohistochemistry (IHC), which is present on about 60-80% of NSCLC tumors. So there was a modest degree of selection of these patients, but a majority of patients would likely be eligible. All patients received doublet chemo with an "old school" combination of cisplatin and navelbine. This is a fine regimen but not commonly used in advanced NSCLC in the US (but still favored as a very good choice in the post-operative setting, since the majority of the best data in this setting is with cisplatin/navelbine). At the time this trial was developed, European oncologists were most commonly giving cisplatin, often with navelbine and gradually giving way in recent years to gemcitabine.

So all of the patients received the cisplatin/vinorelbine chemo combination, and half also received Erbitux as a weekly treatment with it.

Erbitux FLEX trial figure (Click to enlarge)

The only real information in the press release was that the trial showed a significant improvement in overall survival, which was its primary objective. We also know that it included patients with all subtypes of NSCLC, which is particularly important because the subset of patients who are good candidates for Avastin (no squamous cancers, no brain metastases, no history of coughing blood, not on blood thinners...) is probably less than half of the patients out there. However, we don't know how positive this trial really was. The important ECOG 4599 trial that led to Avastin's approval for NSCLC showed a two-month survival benefit, and some even scoff at that. If the Erbitux trial shows a median survival benefit of just 3 weeks, it might be considered statistically signficant but not clinically meaningful, especially if side effects were a very significant issue (rash can be worse than with either Iressa or Tarceva and sometimes very severe). And then there's the fact that the studies with carbo and a taxane (either taxol or taxotere) have looked modestly encouraging at best (reviewed here), with perhaps a hint that some patients, such as those who are positive for EGFR gene amplification by the FISH test, could get major benefit from Erbitux.

We definitely need more information. It's safe to say that US oncologists aren't going to drop carbo/taxol and other much more commonly used regimens to start using cisplatin/navelbine with Erbitux, even though the only encouraging evidence for a survival benefit with Erbitux in lung cancer will be with the cisplatin/navelbine regimen and NOT with a carbo/taxane regimen. However, it's also true that this is the first time we'll have seen any benefit from a combination of an EGFR inhibitor (with a different mechanism than the tyrosine kinase inhibitors Iressa and Tarceva) for a general population in a large phase III advanced NSCLC trial (the INTACT, TALENT, and TRIBUTE trials were all negative, as reviewed here).

We need to learn a lot more about this trial, such as how big the survival benefit was, how the treatment was tolerated, and whether the benefits were seen broadly across many patient types or in more restricted subsets (clinically or molecularly defined). We don't know whether patients who received Erbitux first line ever respond to second lineEGFR tyrosine kinase inhibitors like tarceva. Will there really be a net gain in survival, or was the survival benefit with Erbitux on the FLEX trial only seen because those patients never received an EGFR inhibitor of any type?? Perhaps this is why the US-based trials haven't looked as favorable...

In the meantime, it appears we may have another first line treatment option for patients who are not eligible for Avastin, and a potentially competing targeted therapy option for the subset of first line advanced NSCLC patients who would otherwise receive chemo and Avastin. And because I know what you're thinking, I'll remind you that the Southwest Oncology Group (SWOG) has just completed a feasibility trial called SWOG 0536 that gave chemo (carbo/taxol) with both Avastin and Erbitux:

SWOG 0536 schema ($$!!)

Like a Rolls Royce, if you have to ask the price for this regimen, you can't afford it).

For now, we await more information. But we may have a new (to lung cancer) agent for advanced NSCLC based on this trial.

Next Previous link

Previous PostNext Post

Related Content

Image
Clinical Trials Storytelling 2025
Article
GRACE is pleased to introduce three amazing individuals participating in the 2024-25 GRACE Clinical Trials Experiences Storytelling Program
Article
Imagine your body's defense system, the lymphatic system, suddenly turning against you. This is the reality for those facing lymphoma, a cancer of the immune system's crucial network. This article delves into the complexities of lymphoma, exploring its various forms, from the aggressive to the indolent, and examining the latest breakthroughs in treatment, including the groundbreaking POLARIX trial and cutting-edge therapies for relapsed cases. Whether you're a patient, a loved one, or simply curious about this complex disease, this comprehensive overview will provide valuable insights into the current state of lymphoma care and the promising future of research.
Image
Melanoma Video Library
Video
In these videos, Dr. Autumn Starnes gives an overview of melanoma's prevalence and risk factors. She also discusses the ABCDE method of self-screening for skin cancer, common misconceptions regarding people of color, and melanoma, and how a person can lower their risk of developing melanoma, among other relevant topics regarding melanoma.  To watch the complete playlist, click here. 

Forum Discussions

Can SCLC also be treated with targeted therapy?

Hi amitchouhan,

Welcome to Grace. At this time, there aren't any targeted therapies to treat SCLC, but there are new treatments. Check out our latest OncTalk webinar from December. The last...

I was searching for this, Thank you so much for the info.

Glad to help.  FYI, I just edited the link, which has the agenda and links to oncologists' bios. Plus, the link is also on our home page, https://cancergrace.org/

Hope to see...

Recent Comments

JOIN THE CONVERSATION
Glad to help.  FYI, I just…
By JanineT GRACE … on
I was searching for this,…
By LilahStapleton on
Hi and welcome.  I'm sorry…
By JanineT GRACE … on
Hi amitchouhan,

Welcome to…
By JanineT GRACE … on