On the heels of virtual #ASCO20, AstraZeneca’s ADAURA trial is still the talk of Twitter. The data on using Osimertinib as adjuvant therapy in Stage Ib – IIIa EGFRm lung cancer patients after complete resection was undoubtedly exciting! In the overall population, 89% of patients were disease-free in the Osimertinib group at two years compared to 53% in the placebo group, with an impressive HR of (0.21). Wow!
Ongoing dialogue for this trial includes concerns about costs, endpoints, trial design and overall survival – all important endpoints. However, a critical perspective is missing -- the patient’s perspective regarding treatment and personal goals in this context. I am going to share mine as a patient and advocate.
What I hope readers will take away from my story is that ‘survival’ is more than just a clinical trial number. ‘Survival’ is not just some prescribed value that can be generalized for all patients. Numbers don’t translate or have meaning to a patient’s ‘survival.’ As Solomon said in the film “12 Years a Slave,” “I don’t want to survive - I WANT TO LIVE!”
MY STORY
I lost my dad and two grandparents to lung cancer when I was 13, followed by my mom and aunt Dede, who died of lung cancer when I was in my 20’s. In the 14 years between my dad being diagnosed with lung cancer and my mom’s diagnosis, there wasn’t a single advancement in lung cancer treatment, despite it being the number one cancer killer. In fact, twenty years ago, the only distinction doctors could make was whether a person had small cell or non-small cell lung cancer, and patients only had 3 treatment options; surgery, radiation, and/or chemotherapy.
I started getting periodic scans at age 27, when my mom was diagnosed with lung cancer. My scans were not concerning until 2009, when a nodule we had been following for three and a half years became aggressive, and I was diagnosed with lung cancer at 39 years old. My kids were 6, 8, 10 and 12 — and their only association with this horrific disease was death. They were scared, and my greatest fear was quickly becoming a reality. I was following in my family’s footsteps, and there still wasn’t any promising research that convinced me that the path would change.
I had surgery and was diagnosed with stage Ia adenocarcinoma, positive for an EGFR mutation (EGFR & KRAS were all they tested for). At the time there was some excitement around using Erlotinib as adjuvant therapy. Even though the cancer was stage Ia, I knew I was at risk for recurrence. I didn’t want my kids to ever go through what I went through, so I took Erlotinib (off label) as adjuvant therapy. And it worked…. until I stopped taking it.
Eight months after I stopped taking Erlotinib there was a new nodule on my scan, and four months later I had surgery to remove it, another stage Ia EGFR mutant lung cancer. The surgery was successful, but unfortunately, there was new tumor growth on my post-op scan, and even more on my next scan. I was lucky the cancer was contained to my chest, but after looking closer at the pathology of the two resections we learned it was the same disease and not a new primary.
Erlotinib was still the only TKI approved for EGFR mutant lung cancer in early 2013. SBRT for intrapulmonary metastasis wasn’t a thing, but risks were low, so my care team and I decided it was a better option for me rather than going back on Erlotinib. I was willing to take the risk and was fortunate to use SBRT as needed for five years. The wait, watch, treat with local therapy as needed approach ended last year when one nodule continued to misbehave. Nothing else was imminent, but SBRT was risky because of the location of the nodule. It was time to treat the disease, not the scan. Going back on a TKI was definitely a hard pill to swallow (literally), but it was the first time in 10 years I was not overcome with fear. There was HOPE. Osimertinib was now in the ‘toolbox’ of EGFR targeted therapies.
ADAURA
There have been so many advancements in lung cancer treatment over the past decade, but few in the early stage space, particularly in lowering the (high) risk of recurrence for patients with early-stage lung cancer. My concerns and excitement about the ADAURA results come from my experience as a child, caregiver, patient advocate, research advocate, patient and on behalf of ALL lung cancer patients.
My concerns as a research advocate:
1. Adjuvant therapy is for curative intent after presumed curative treatment. There’s a significant difference between outcomes of overall survival and disease-free survival, and as of now we only know that Osimertinib can delay recurrence. Patients need to understand both when making a treatment decision. Osimertinib doesn’t come without cost, literally and figuratively.
2. Important questions will remain unanswered. Which patients have recurrence while taking Osimertinib? Which will have recurrence after stopping therapy? Is there a pattern of recurrence? What are the resistance mechanisms, and should patients have chemotherapy first (I would!), etc.? Those answers could provide the information needed to stratify patients who will benefit and avoid unnecessary harm to patients who are truly cured.
3. Quality of Life. Please never minimize side effects. Tolerable is relative to each patient. In addition, many patients don’t fully disclose side effects to their health care team out of concerns of being taken off a treatment or trial, a dose reduction or they are just determined and stubborn. I am one of those patients. Plus, it’s too early to even understand long-term or late effects of treatment.
4. Access and Affordability. It’s not enough to develop new treatments if they will only benefit patients who have access to, and can afford, cutting edge care. We need cancer care and treatments that ALL patients can access.
I have other concerns surrounding endpoints, data, and whether prolonged exposure delays or shortens the time to recurrence. I know many oncologists do as well, but the important part now is to step out of the scientific box and think about the vulnerable and scared person/patient, and their family, in front of you.
MY JOURNEY AS AN EXAMPLE
My care team has always known that my preferences in treatment had to be guided by the impact it would have on my family, and at times that has meant thoughtful discussion about my goals. I want to give an example.
My oncologist (Phil Bonomi) knew I wanted adjuvant therapy after my first surgery, even though it wasn’t standard of care. At my first appointment Dr. Bonomi said, “I need to tell you that if it were me or someone in my family, I wouldn’t recommend Erlotinib as adjuvant therapy. But, let me ask you a question: What are your goals?” I remember being thrown off guard and saying, “I just need to do everything in my power to live to raise my children.” Without hesitation he said, “I recommend you take Erlotinib as adjuvant therapy”. I asked him how he could change his mind like that. His response was, “I didn’t change my mind. For YOU, the benefits are unknown, but risks are low, and your emotional well-being is just as important to me as your physical well-being.” He saw me. He heard me. He treated me, not just the lung cancer.
As you know, the cancer came back. Was it worth the excruciating mouth sores, painful rash, paronychia, etc.? It would be easy for me to say no now. But Dr Bonomi was right about my emotional well-being -- if I hadn’t done everything in my power and taken Erlotinib, I don’t think I could look my kids in the eyes and not feel overwhelming guilt at ‘what could have been’.
APPLYING SCIENCE IN CONTEXT OF EACH PATIENT
After my second surgery, my kids would ask me what will happen when the doctors can’t take any more of my lungs. It killed me because I lived the horror of that reality with my aunt Dede, whose third stage I cancer killed her because she didn’t have enough lung capacity to survive another surgery!
Erlotinib didn’t result in a cure for me, but I’ve lived longer than my aunt Dede did. Is that because Erlotinib altered the course of the disease? Did taking it prevent the disease from being more aggressive and metastasizing to other organs, bones, or the brain? I don’t know, but it very well could have delayed recurrence, and is what bought me the time I had off systemic treatment. THAT is meaningful.
Treating lung cancer is more complex and complicated than ever before and scientific evidence is often incomplete and/or conflicting. Knowing when to apply therapy is an inexact science at best and there often aren’t concrete rights or wrongs. The RIGHT thing is knowing the medical data and applying it in the context of each one of your patients.
HOPE MATTERS
Hope is a powerful force that lung cancer patients and our families desperately need. Hope means different things to different people, but for all of us it is a vital emotion in the face of a lung cancer diagnosis. Hope Matters!
My family history illustrates Hope. My dad died at 41 years old, just 3 months after he was diagnosed with lung cancer, and my mom died at 54 years old, just 6 months after she was diagnosed with lung cancer. Adjuvant therapy may not have changed their survival, but what’s even more important and meaningful is; maybe my dad would have lived just a few more weeks to see me graduate 8th grade and maybe my mom would have lived six more months and been there for the birth of my daughter. Many more milestones were stolen from my parents, but those are the ones that leave me with profound pain and emptiness because they were so very close.
IN SUMMARY
Like many of you, I struggle with the ADAURA trial. Like many patients, I struggle with treatment decisions and depend heavily on guidance from my doctors. Knowledge, experience, access to research and cutting-edge treatments are all important in providing the best care, but so is believing that the patient’s spirit, family, dignity, and goals are just as important. Through my advocacy work, I’ve learned that I can’t make my own culture, preferences, or beliefs the standard. You must take steps outside of your comfort zone to try and understand what’s meaningful to each patient, and together make a treatment decision.
You may not save every life, but if you help your patients find their Hope, I promise you will make a difference in every patient’s life.
Thank you for fighting with us and for us!
