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)

 

Tarceva for Advanced Squamous NSCLC: Recalibrating Expectations

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

When most oncologists think about the EGFR inhibitor tarceva (erlotinib), they think of the uncommon but very memorable patient who has a spectacular response within a few weeks of starting it, then continues to do well on it for a year or more. These patients are most commonly never-smokers, often Asian, and almost invariably have an adenocarcinoma. In contrast, many oncologists perceive there to be little to no value in giving tarceva to patients with squamous tumors, and many don’t even bother to offer it to these patients. However, it’s worth highlighting the evidence that suggests a meaningful survival benefit, even if it falls short of the “swinging for the fences” idea we have when we give tarceva to some patients. At the same time, we need to remember that agents like Alimta (pemetrexed) and Avastin (bevacizumab) are not generally indicated or used for patients with squamous NSCLC tumors, due to efficacy or safety concerns, respectively. Options in advanced NSCLC are limited, but more so for patients with squamous tumors, so we need to ensure that we don’t leave good alternatives unused. Throughout all of this work it’s important to underscore here the difference between response rate and survival, something that many oncologists still forget when they dismiss a drug for not having a high enough response rate against a certain type of cancer. But it’s become increasingly clear in the past few years that patients with lung cancer can receive a significant survival benefit in the absence of major tumor shrinkage, and that’s not hard to imagine: if the cancer would otherwise be growing, maintaining stability is a relatively good thing, even if it falls short of major shrinkage. And to fulfill the clinical trial criteria for even a partial response, a tumor needs to shrink by about 50% of its volume. When I tell a patient that his or her tumor has shrunk by about 30%, a “minor response” that is still generally considered stable disease in clinical trials, we’re all pretty happy with that and don’t toss that treatment aside just because the tumor didn’t shrink by 50% or more.

One of the earliest posts I did, now nearly three years ago, was on the question of whether the oral EGFR inhibitors like tarceva and Iressa (gefitinib) offer any benefit to a patient population broader than Asian never-smoking women with an adenocarcinoma, or especially BAC. Is this is a class of drugs that provides a huge benefit for 10% of North American patients (a higher proportion in Asia) but nothing for anyone else. The short answer was that there is a definite survival improvement in the broad population, which tends to be a different kind of benefit, more modest and not especially long lasting, but still worthwhile. Since that time, we’ve also learned that alimta (pemetrexed), one of our most commonly used agents in advanced NSCLC, doesn’t provide any apparent benefit for patients with squamous NSCLC, so our options are more limited than they were then. To recap a few highlights from that post, the original randomized trial of tarceva vs. placebo in 2nd or 3rd line NSCLC showed that although patients with an adenocarcinoma had a response rate more than three times higher than that seen in patients with a squamous tumor, they had the same improvement in survival, illustrated by the separation of the survival curves for tarceva vs. placebo, as well as in the “hazard ratios”, where a decimal lower than 1 reflects a relative improvement of experimental treatment to the standard arm. tarceva-histol-diffs-rr-vs-os (click on image to enlarge) So the survival benefit, reflected in the separation of those curves, is remarkably similar in the patients with a squamous tumor, even if far fewer have tumor shrinkage. It’s not going to be a home run, but they’ll get the same modest improvement in survival with less fanfare that most people who don’t have a “wow” response do. In fact, the survival benefit is quite striking for tarceva in healthier (performance status 0 or 1) patients who received tarceva as second line therapy. Compared with placebo, it more than doubles median survival: tarceva-squam-ps1-2-2nd-line Patients who were more debilitated and who received it as third line therapy didn’t get the same benefit, but that’s pretty much what you’d expect from any agent. Impressively, even male current or ex-smokers with a squamous NSCLC got a more than two month improvement in median survival with tarceva (2nd or 3rd line): tarceva-male-squam-smokers As we now move into an era where maintenance therapy is being used more and more for advanced NSCLC after the first 4-6 cycles of treatment, we can see that the treatment options for what to use are very limited. For patients with squamous NSCLC, we could give taxotere, but the trial that tested it as a maintenance therapy actually failed to show a significant survival benefit (though I would consider the trial underpowered and not positive enough, but with an absolute improvement in overall survival of >2.5 months, still clinically significant). It’s also felt by most oncologists and patients to be pretty challenging for maintenance or second line therapy. Though I’d consider it to be a perfectly acceptable option, it’s not without its challenges. Tarceva has also been studied in a placebo-controlled trial as maintenance therapy after four cycles of first line therapy, and some updated results from that trial were just presented at the European Society for Medical Oncology Meeting in Berlin. The trial demonstrated an overall survival benefit of 1 month that was statistically significant, and the same modest (14%) improvement in survival was seen in the squamous patients. Frankly, to me this looks like a little less than I’d have expected based on the curves above, but it’s something. Not everyone will consider it worth the costs, financially or in terms of side effects, to gain a benefit much more likely to be weeks to a few months rather than the eye-popping months to years we see more commonly in patients with adenocarcinoma NSCLC, but when there are few tested and approved options to turn to tarceva can provide a clinically meaningful if not staggering benefit. It’s certainly an oversimplification, to the detriment of patients, when some oncologists dismiss EGFR inhibitors as simply ineffective for patients with squamous NSCLC.

Next Previous link

Previous PostNext Post

Related Content

Article
Advance directives are a powerful way to take control of healthcare choices. These documents allow you to outline preferences for medical care and specify end-of-life wishes. These documents can also be a way to appoint loved ones who you would like to help with these decisions, such as a healthcare proxy (someone to make decisions on your behalf, if you cannot). As cancer treatments can involve aggressive treatments and/or complex medical management, having advance directives ensures that your desires regarding treatment options and end-of-life care are clearly communicated. 
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
Foro de Pacientes de Terapias Dirigidas de Cáncer de Pulmón
Video
¡El vídeo completo bajo demanda está disponible para verlo!

Forum Discussions

Hi Bluebird,  Welcome to GRACE.  I'm sorry you're going through this scare and hope it's just inflammation from an infection you didn't know you had. 

 

A CT would be the...

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...

Thank you, Janine, for answering so rapidly. I am aware that my nodules are small, but they scare me all the same. Your words that nodule measurements may vary somewhat when...

Hi Barbro,  I'm sorry you're worrying about this, and don't feel like you can discuss this with your doctor.  Speak to your doctor about this.  Let them know your worries and...

Recent Comments

JOIN THE CONVERSATION
Hi Bluebird,  Welcome to…
By JanineT GRACE … on
Hi Barbro,  I'm sorry you're…
By JanineT GRACE … on
General Lung/Thoracic Cancer
By Barbro Kristin… on
My first thought is to ask…
By JanineT GRACE … on