A Patient's Perspective on Biomarker Testing and Clinical Trials

Nikki Martin, LUNGevity's Director of Precision Medicine Initiatives
Melissa Crouse
Melissa Crouse

One of the most important steps that someone with advanced-stage non-small cell lung cancer (NSCLC) can do for their care is have comprehensive biomarker testing at diagnosis and at progression/recurrence of their lung cancer. A biomarker is a molecule that can be measured to provide information about your unique disease. The results of this testing will tell you and your care team whether you have any one of a number of possible mutations and what your level of a certain protein is. This is critical information for making optimal treatment decisions. Specifically, the two types of biomarkers that are relevant to lung cancer patients are:

  • Mutations within the cancer DNA (e.g., EGFR, ALK, ROS1, RET, etc., used to determine whether there is an appropriate targeted therapy)

  • High levels of a certain proteins (PD-L1, used to decide whether a patient is likely to benefit from immunotherapy)

Some patients, for example, may find that they have a mutation that has one or multiple FDA-approved targeted therapies to consider as treatment options; patients with ALK, EGFR, ROS1, BRAF V600E, and NTRK1 fall into this category. Other people may find a mutation with a therapy in development in a clinical trial. In some cases, the patient is diagnosed with a mutation that has neither an FDA-approved therapy nor a clinical trial in progress for a therapy in development. For these patients, the biomarker testing results indicate a known mutation but no clear path forward.

This was the situation for Melissa Crouse. Melissa, a former middle school teacher, is a 14-year lung cancer survivor and leads a fulfilling life in Cape Coral, Florida.  In November of 2012, nearly seven years after she was initially diagnosed with Stage 2A NSCLC, her doctor gave her the mixed news that she had the RET mutation, which at the time didn’t have an approved therapy or an available clinical trial.

 

Melissa, tell me a little about your initial diagnosis.

I was diagnosed in 2005 with stage 2A NSCLC when an x-ray showed a tumor in (the upper lobe of my left lung). At that time, I had an upper left lobe resection and 16 lymph nodes removed, followed by six courses of chemotherapy. After my diagnosis, the hospital ran single-gene biomarker testing for the EGFR mutation. This was the only testing they knew to do then, and those results were negative. I was fine until 2009 when it was discovered that my cancer had metastasized to my liver.  After that, I had every treatment you could have imagined, including stereotactic radiation, which I’d do in the morning before going to school, and proton beam radiation. I’ve also almost died twice from treatments; in 2009 and 2012, I was being treated so aggressively that I landed (once) in the hospital and once in the ICU, but I managed to pull through.

 

What happened then?

After this period, I started seeing a well-known lung cancer oncologist, Dr. Jeffrey Engelman, previously with Mass General.  He performed comprehensive biomarker testing on my tumor for ROS1 and MET, among others, and in November 2012, he discovered that my tumor tested positive for the RET marker.   When Dr. Engelman got the results, he called me, excited like a kid in a candy store. He said, “I found your mutation! You’re RET-positive!” And my reaction was, “All right. So what does that mean?”  You know, at the time, there was not too much mention of targeted therapies. It was like, “So what?” There wasn’t a RET therapy approved or anything even in clinical development.

 

That sounds like a tough place to be. You have a mutation, which your oncologist is excited about, but there’s no clear path for a treatment. How did you handle that?

Even though there wasn’t anything being developed specifically for the RET mutation, there were drugs that I classified as “tinibs” (multi-kinase inhibitors because they work to block multiple kinases, or enzymes, that are involved in the growth of tumors) in clinical development for other mutations, and my oncologist  thought they might also impact my RET-driven cancer. Over the course of several years, my oncologist put me on four multi-kinase clinical trials, and these kept me alive for six years. I was even put on Opdivo (an immunotherapy drug) for a while. None of the clinical trials or the immunotherapy really worked, and they all made me really sick. (The multi-kinase trials were not specific to the RET mutation and had severe side effects.) Emotionally, I felt defeated. But I continued teaching Middle School Orchestra and Chorus throughout this time, and that helped me stay as normal as possible with my life. Working was my lifeline and gave me normalcy during this difficult period.

 

During this time, were you thinking about the RET mutation, or had you forgotten about it?

No, I hadn’t forgotten about it. By this time, even though I was still at Mass General, I had a new oncologist, Dr. Justin Gainor. We had hit a wall with my options. I remember asking Justin about next steps, and he told me that there was a new clinical trial for RET starting up. Although my hospital, Mass General, was going to be a site for the trial, it wasn’t open yet. He wanted to get me on the clinical trial right away, and he knew the oncologist who was the principal investigator for the recently opened RET clinical trial at Memorial Sloan Kettering In New York City. So, he introduced me to Dr. Alex Drillon, and that’s the trial I got on in July 2017.

 

How are you feeling now that you’ve been on this RET clinical trial?

It was two years in July 2019 since I started this study and I feel remarkably well.  So much better than when I was on those “tinibs”!  I enjoy a good quality of life and now spend as much time as possible with my grandchildren. I’m actually able to function and do “normal” things like meeting friends for lunch, going to the beach, going to church, and shopping. I also participate in the Pedaling for Parkinson’s (I was diagnosed with Parkinson’s 12/18) and the Livestrong Exercise classes at the YMCA - activities I couldn’t even think about with the other clinical trials I’ve been on.  I was just too sick.  Now, things are very different.  I do experience fatigue, but that’s nothing compared to the other trials.  

 

Do you have a message for patients and caregivers who might read this?

My advice is to make sure that you have comprehensive biomarker testing done to see if you have any sort of mutation and to see what the level of your PD-L1 protein is, and go from there. It’s key for patients to get the comprehensive biomarker testing because it can reveal information about your cancer that can save your life. I’ve had biomarker testing performed five times: once at diagnosis, with the EGFR biomarker testing, and four times with comprehensive biomarker testing at every recurrence of the lung cancer. Because my lung cancer has spread to my liver, they’re able to pull tissue from my liver. They just go in there with this little claw.  

I like the term “comprehensive ” because the type of testing you can get is not the same across the board. I’m finding that people who live in remote areas run into problems accessing biomarker testing. I spoke with a woman in California who went to her doctor asking about comprehensive biomarker testing, and her doctor said, “Oh, you don’t need that.” So, there’s another bridge to cross there, helping people who see physicians who aren’t educated about the need to perform this testing.

 

Do you have a message for people who are now in the situation you found yourself in in 2012 who find a mutation but no clinical options?

Don’t lose faith, and hang in there. You never know when somebody is going to discover or create a treatment for that mutation. I’ve basically lived the research because it’s been 14 years now. I’ve seen all these developments happen, and I’ve been a part of it by participating in these clinical trials. I tell people not to be afraid to enroll in clinical trials. People have the wrong perception of clinical trials. But clinical trials kept me alive. Since there wasn’t anything available for RET, it was like they were throwing everything at me. Spaghetti on the wall to see what stuck. Then, finally, a RET clinical trial became available.

Interested to learn the perspective of Melissa’s primary oncologist at the time, Dr. Gainor from Massachusetts general Hospital in Boston? Check out his blog, An Oncologist's Perspective on Comprehensive Biomarker Testing.

If you are considering participating in a clinical trial, there are several resources in addition to your healthcare team to help you find one that may be a good match. Check out Clinical Trial 101 to learn more or our Clinical Trial Finder to see if you qualify.


Nicole MartinNicole Martin is LUNGevity's Director of Precision Medicine Initatives .

Blog category: 
-> Survivorship
-> Biomarker testing
-> Treatment

Comments

What an ordeal....almost like walking thru fire or on burning coals....But look at you now! An Advocate for us all working tirelessly to help so many of us with NSCLC. Bless you Melissa. gdlemaire

Add new comment

print