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Marcia Horn Discusses Advancements in EGFR Exon 20 Insertion+ NSCLC and the Importance of Community


There are promising developments in the pipeline for EGFR exon 20 insertion–positive non–small cell lung cancer (NSCLC), and groups like The Exon 20 Group can help ensure patients are getting access to programs to navigate their care.

Although the EGFR exon 20 insertion–positive mutation accounts for a small minority of patients with non­–small cell lung cancer (NSCLC), there is a promising pipeline, said Marcia Horn, JD, executive director, The Exon 20 Group, and president and CEO of ICAN, International Cancer Advocacy Network.

In an interview with The American Journal of Managed Care® (AJMC®), Horn discussed implications of treatments for these patients, the biggest impacts on quality of life, the importance of having a community of patients and care partners, and more.

AJMC®: Despite NSCLC being one of the most common forms of lung cancer, the EGFR exon 20 insertion–positive mutation accounts for only about 1% to 2% of NSCLC patients. What are some implications of treatment and therapy that are specific to this small subset of patients compared with the treatment of NSCLC at large?

Horn: Patients with EGFR exon 20 insertion have a very promising drug pipeline in addition to 2 critically important drug approvals. Few rare mutation groups see this so early on. Thanks to top molecular profiling laboratories and next-generation sequencing (NGS), more and more lung cancer patients are being diagnosed with actionable mutations. So now, in part because of the tremendous advances in the field, when EGFR exon 20 insertion mutations are diagnosed, there is a swim lane that is far, far longer than it was just 6 years ago when we launched the Exon 20 Group.

The Exon 20 Group was founded in March 2017 by 2 brilliant dynamos: the late Kevin M. Hanlon and his brother, Robert T. Hanlon, PhD, at ICAN, International Cancer Advocacy Network, a 501(c)(3) cancer patient advocacy organization. ICAN has been doing direct navigation of pan-heme, pan-tumor, and pan-care cancer cases since 1996, and we had always attracted rare mutation cases. Kevin, a patient diagnosed with EGFR exon 20, was referred to us by Carey Gold, a stellar patient advocate in New York City. Our ICAN Trustees chair, the indefatigable Sherry Weinstein, secured instant unanimous board approval for the Exon 20 Group’s launch.Kevin passed in 2019, and the memory of Kevin inspires us every day.We try to live up to his vision of top-notch patient care and accelerated drug discovery and development for exon 20 patients by working on what we call “Kevin Time.”

The Exon 20 Group quickly became a multistakeholder global coalition: patients, care partners, community oncologists and thoracic oncologists in academic medical centers, molecular profiling labs, pharma and biotech companies with drugs in the exon 20 pipeline, and scientists in leading laboratories. We would love to have payers, medical directors, and Medicaid directors join the Exon 20 Group as members as well. We serve 72 countries at this point, and we’re growing daily. We want to be serving 2500 EGFR exon 20 and human epidermal growth factor receptor 2 (HER2) exon 20 insertion patients by the end of 2023. We currently offer more than 20 different services to exon 20 patients and membership in the Exon 20 Group, and access to these services is free.

Here are some take-home messages for payers, medical directors, and health care providers:

  • All: Please refer any exon 20 insertion patient to the Exon 20 Group, or please make sure that the community physicians and thoracic oncologists you are dealing with know about the multistakeholder Exon 20 Group.
  • All: Approve/order NGS testing for NSCLC patients on diagnosis, and to assess on progression whether there is an EGFR resistance mechanism in play. If polymerase chain reaction is used to diagnose disease, it can miss half the EGFR exon 20 insertions that NGS would otherwise find. If a patient is deemed a classically mutated EGFR patient (deletion 19, L858R), you don’t want them to miss out on the specialized exon 20 insertion drug pipeline, which could save the payer hundreds of thousands of dollars on successive hospital admissions and stays, compared with second-line chemo regimens with scant response rates.
  • Payers: If a medical oncologist is deciding on the first-line regimen for a newly diagnosed patient, please confirm that they are considering the phase 3 trials in the exon 20 field prior to defaulting to the chemo doublet of pemetrexed-carboplatin for these rare patients. Entering a phase 3 trial in this area could well mean bending down your cost curve and extending survival and quality of life.

AJMC®: What are some of the biggest impacts of quality of life on patients with EGFR exon 20 insertion–positive NSCLC?

Horn: The good news is that they’ve been diagnosed with an actionable mutation where the drug pipeline, with proactive tox management, can offer them the possibility of maintaining productive and active lives.

While the drugs in the exon 20 insertion field are essentially tolerable, each has its own set of side effects, as one would expect. It’s very important that the patient not suffer in silence about side effects. So whether it’s rash, gastrointestinal distress, fatigue, pain, paronychia, mouth sores, or another issue, we want to make sure that the patient always keeps the oncology team or the study coordinator abreast of tox issues that are not being well managed. Our wonderful oncology nurse, Carmi Fazio, RN, is a great source for tips that can help an individual patient’s experience on any drug in the standard arsenal or in the trial setting.

The late Elena Siltanen, MSc.Pharm, the inaugural chair of our Angel Buddies Program, was an inspiring and proactive HER2 exon 20 insertion patient who wrote for us the Collateral Guide to Exon 20 Medications. This has been an indispensable primer for our patients, with great advice that is relevant to all exon 20 drugs.

AJMC®: How can care navigation or case management improve treatment outcomes for EGFR exon 20 insertion–positive NSCLC?

Horn: We specialize in direct patient navigation at the Exon 20 Group. Thus, care navigation and case management are both essential to a patient journey of “No Regrets,” which is what we are aiming for. Our goal is that the patient and family never find themselves in a position of saying, “Well, we should have done this…”

We outline for the patients the substantive advances in the field that have provided concrete hope of life extension and improved quality of life. These advances are tangible and not false hope. We take the position that exon 20 is very likely to become a chronic and manageable disease in the foreseeable future as the drug pipeline expands. The pipeline is moving way too fast to bet against this.

At the onboarding session with a patient, we discuss the first 2 approved drugs for EGFR exon 20 insertions: Janssen Oncology’s amivantamab-vmjw (Rybrevant) and Takeda Oncology’s mobocertinib (Exkivity, formerly TAK-788), both approved in 2021.

We stress the importance of having a good community oncologist who can work well, on a shared management basis, with a thoracic oncologist in a comprehensive cancer center who is the principal investigator of an exon 20 trial at that center. The patient may need to screen for that trial right away or at the next pivot point of disease progression. Community oncologists should know they can quickly learn and excel in the exon 20 field.

Our direct patient navigation services also include our oncology nurse Carmi, who I mentioned earlier. Carmi never fails to suggest something that is useful to an exon 20 patient in the throes of needing additional side effects mitigation. When we have a particular question about a never-seen-before mutation, I reach out to 2 outstanding scientists, the chair of our Biomarker Council Scott M. Kahn, PhD, who heads Alykomed Global Solutions, and our vice chair, Eric J. Thompson, PhD, who is vice president of translational medicine at CIRCULOGENE.

Community practices and academic medical centers are very much on overload and thus getting answers back to a patient via a patient portal is sometimes taking longer than we all want to see.

Many days we feel we are adjunct to the highly stressed study team or the community oncology practice. The Exon 20 Group can often pick up where they left off and reassure the patient about options to discuss with the team, or interim strategies to use to help mitigate a particular side effect. We have often found this to be critical in maintaining patient participation in clinical trials.

AJMC®: Why is it important to have a community of patients and care partners in the management of diseases such as EGFR exon 20 insertion–positive NSCLC?

Horn: Exon 20 patients are a close family and a very caring community. In addition to our direct patient navigation services, which operate 24/7/365, our lead patient advocates, care partner advocates, and public policy advocates have been absolutely essential in helping build our Exon 20 Group community—Kristen Leniz; Caren Suesserman; Susan Johnson; Lauren Conley; Katina Bland; Ioana Grigorescu; Steve Horn; Elena Gershanov; Matt Targett, PhD; Sandy Kitchner; John Ryan; Paul Hutter; Louise Kuchel; and Ashraf Abdel-Ghany, MD. We pair new patients with veteran patients or seasoned care partners in our “Angel Buddy” program. We offer a weekly virtual meeting where whatever is on the patient or care partner’s mind gets discussed. We have the Exon 20 Warriors on Inspire, the social media platform for rare mutation communities, as well as 19 private, closed Facebook groups. Admission is strict to protect patient privacy.

AJMC®: What are some ways that patients and care partners can best engage in these communities?

Horn: Here are some take-home messages for patients and family members:

  • Join the Exon 20 Group and let us know if you want to be paired with an Angel Buddy. Choose whichever of our social media support groups interest you.

    It’s never too early to join the Exon 20 Group. We think it’s absolutely critical to interact with the patient as close to diagnosis as possible, and we are excited about getting more Stage 1B patients as new members who are post-lobectomy and who are in a position to benefit from our services from the start.
  • Please take advantage of the survey research opportunities that we have (anonymous, of course). These will advance global oncology’s understanding of the EGFR exon 20 patient population and exon 20 insertion mutations. We have some major research studies coming up.
  • We are continually recommending patients and care partners to serve on patient advisory boards.

AJMC®: What is the importance of clinical trials and research in exon 20 insertion–positive NSCLC?

Horn: Clinical trials and research are centrally important, and virtually every phone call we have includes a discussion of clinical trials, as patients are always eager to get updates about the drug pipeline. We explain the ongoing clinical trials pipeline and the rapid pace of discovery and development. The 2021 annual meeting of the American Society of Clinical Oncology (ASCO) was dubbed “the Exon 20 ASCO” because of all this progress.

We are also working hard to make decentralized trials become the norm. We know this can happen, as we had our first successful experience last year—kudos to Black Diamond Therapeutics for decentralizing and delivering a much-needed trial to the medical center that was only minutes away for one of our patients. And imagine what a national effort of decentralized trials combined with liquid biopsy could do for underserved patient communities in terms of improving health equity for patients with all cancers.

What we worry about are patients who don’t yet know about the Exon 20 Group. Are we only helping the tip of the iceberg of patients, the most proactive of the proactive? Where is everyone else? We certainly hope they are with proactive community oncologists who understand the exon 20 clinical trials pipeline. But we are finding that it is not unusual for a year or more to have gone by before patients are properly and finally diagnosed via NGS and thus able to be prescribed specific treatments for their exon 20 insertion driver mutation.

That is why it’s essential that we change the paradigm of how patients connect to rare mutation support groups like the Exon 20 Group. I currently serve as vice president of the Biomarker Collaborative, a nonprofit organization dedicated to connecting patients to the appropriate rare mutation cancer support group. This past January, the Biomarker Collaborative and its force-of-nature president, John Hallick, who is president of the MET Crusaders (along with his co-president—the much beloved Gina Hollenbeck of ALK Positive, of cherished memory), announced a partnership with NeoGenomics (thanks to Neo’s Rachel Malmberg). Now, Neo identifies the appropriate biomarker support group to the patient and clinician receiving the company’s molecular profiling report. This is a huge advance, and every tissue profiling NGS lab and liquid biopsy lab should follow suit. The more the better.

AJMC®: What are some ways we can encourage patients to seek out and participate in these trials and research?

Horn: Participation in clinical trials can be greatly increased with specific, concrete actions.

Take-home messages for patients and their care partners (and clinicians if the patient does not ask):

  • Ask about the 2 approved exon 20 drugs as well as clinical trials at each pivotal appointment with your oncologist. The Exon 20 Group is here to help you understand and discuss clinical trials through our clinical trials matching services so that you can ask the relevant screening questions of your oncology teams.
  • Ask your oncologist about ordering an NGS tissue and/or liquid biopsy on disease progression if you have unambiguous disease progression on the drug regimen that you are on (or you have been experiencing rapid progression on successive regimens and don’t know why). We offer molecular profiling laboratory matching services at the Exon 20 Group.
  • Ask about expanded access programs—our exon 20 pharma and biotech companies have been exceedingly generous. The Exon 20 Group’s expanded access matching services shine the light on compassionate use programs and interact with patients, clinicians, and companies throughout the process. Bravo to Janssen Oncology, Takeda Oncology, Spectrum Pharmaceuticals, and Cullinan Oncology for their generous life-extending early access programs reaching many countries.
  • Ask about financial support and additional services offered by Janssen Oncology and Takeda Oncology—the Janssen Compass Program and Takeda Oncology’s Here2Assist Program both provide excellent resources and assistance.

Take home messages for payers:

  • Cover NGS on diagnosis. We all know that if it were a world leader there’d be tissue and/or liquid biopsy molecular profiling ordered immediately, with top oncology teams pouring over the resulting genomics, not to mention the proteomics, transcriptomics, and immune cell studies. We applaud our friends at the American Cancer Society-Cancer Action Network (led by Pam Traxel) for spearheading the transformative biomarker testing bills that might end up before a legislative committee in your state.
  • Cover NGS molecular profiling throughout the patient journey at important points of disease progression. Set in place automatic pre-authorizations for orders for Foundation Medicine, Caris Life Sciences, Guardant Health, NeoGenomics, and other top laboratories’ reports.
  • Cover clinical trial participation. The multiplicity of magic bullets we need to cure cancer will all be found in the clinical trial setting. We are very grateful for Medicaid entering a new era of covering cancer clinical trials.
  • Ask if the physicians you deal with are connected to the Biomarker Collaborative which serves as a big funnel to match patients with the appropriate rare mutation support group on a pan-heme, pan-tumor basis that will ultimately be international.

Take home messages for industry:

  • Pharma and biotech companies should continue providing the Exon 20 Group and other interested rare mutation groups with detailed clinical trial site info and updates so that we can immediately contact a principal investigator or a study coordinator to let them know that a patient will be setting up an appointment to discuss trial screening.
  • Keep your clinical trial submission to clinicaltrials.gov up-to-date and be as specific as possible. Inclusions and Exclusions should not require guesswork or subsequent calls to the company. Name the prior drugs that are excluded, as thoracic oncologists and community oncologists need the specifics.

    There is no excuse in saying “clinical trial recruiting site” in your Contacts section when you should be naming the principal investigator and the study coordinator at the particular medical center, providing full contact information.
  • Make sure you have broadened eligibility requirements and have not posed an undue clinic visit burden or asked for a needless invasive biopsy as a condition of screening when a biopsy was taken weeks earlier and should be given full credit.
  • Have you thought of every possible way to decentralize your trial or open a concurrent expanded access program?

AJMC®: What are the largest areas of unmet need in the EGFR exon 20 insertion–positive NSCLC space?

Horn: Clinicians and Researchers: No question about it: We need real solutions for lymphangitic carcinomatosis, leptomeningeal disease, brain metastases, strokes, seizures, and pneumonia to name a few (and I might add, funding, funding, funding to support the Exon 20 Group’s vitally important research collaborations on a host of issues affecting ongoing discovery and development of exon 20 therapeutics!).

A critical area of anticipated unmet need as the exon 20 field develops will be the necessity to combine drugs based on the relevant molecular alterations in the patient’s molecular profiling reports, which often show important co-driver alterations that should be targeted to optimize response.

A practice-changing trial that demonstrated that combinations of matched therapy could be given safely and improved patient outcomes was the I-PREDICT TRIAL (NCT02534675), led by Razelle Kurzrock, MD; Jason Sicklick, MD; and Shumei Kato, MD, at the University of California San Diego (see also publications in Nature Medicine, Genome Medicine, and Nature Communications). Kurzrock, a terrific mentor and a giant in precision oncology, is well known for innovative trials and has more than 900 publications on PubMed.gov and is listed by Web of Science Clarivate as one of the most cited scientists in the world.

Because of pan-tumor patients that ICAN referred over the years to I-PREDICT, we have seen extended survival and quality of life due to the investigators' resourcefulness and expertise in combining drugs and matching them to the full profile of molecular alterations.

Payers: You can bend the cost curve down if you have the vision to cover patients who are working with oncologists who understand molecular medicine.

Industry: We continually talk to pharma and biotech companies about broadening eligibility requirements for clinical trials, with leptomeningeal disease cohorts at the top of the list. We want to see cohorts for heavily pretreated patients as well. And since we have seen many patients with synchronous primary cancers, we need trials to include those patients in special cohorts, as their clinicians are more than able to evaluate which concurrent cancer is the bigger foe (chances are public enemy number 1 is the EGFR exon 20 insertion–driven cancer). Excluding a patient with EGFR exon 20 who has a concurrent stage 1 breast cancer where there is scant chance of recurrence, and whose top breast oncologist has determined needs no treatment post-lumpectomy, is tragic.

Another unmet need right now is the understaffing at academic medical centers and the staffing shortage throughout US oncology. It just kills us when a top principal investigator can’t take on a second exon 20 clinical trial because “it’s a competing trial.” We need every agent in this arena to succeed.

There is no upper limit to the number of drugs this disease needs. We have seen mindboggling numbers of individual EGFR exon 20 variants and intertumoral heterogeneity and intratumoral heterogeneity. Some patients will go a few months on a drug, others will go years, and they might have the same exon 20 insertion but different molecular co-alterations and different immune systems. Each successive drug regimen offers a stepping stone that might give the patient more quality of life with more life extension.

AJMC®: What are you working on for EGFR exon 20 insertion patients that you are excited to share?

Horn: One of the most exciting things we are doing is our Exon 20 International Research Consortium (Ex 20 IRC). We will be expanding the consortium of physician-scientists and scientists involved in exon 20 research in the coming year, so if anyone has colleagues to suggest, please contact us. Our visionary Exon 20 Group chairman Bob Hanlon, and our 3 Ex 20 IRC chairs, Afshin Beheshti, PhD; John W. Lawson, PhD; and Stephen Baylin, MD, are all out-of-the-box thinkers determined to make a difference. We have excellent research collaborations we want to fund, and we need $5 million to make that happen.

We will also be working to formalize our ad hoc molecular tumor boards on complex cases in the coming year.

AJMC®: Final thoughts?

Horn: All in all, this is an exciting and rewarding time to be battling exon 20 insertion mutations—whether as a physician-scientist or researcher developing and evaluating new therapeutics, a clinician determining the best treatment for each patient, or a patient advocate helping patients fight this fight in order to survive, and indeed even thrive, until drug combinations with our approved exon 20 drugs as well as new therapeutics become available. To be as effective as possible, we need support not only from funders, but also from the payer community because our goal is to be the first rare mutation organization to see total cure.

Gratitude is a guiding principle at the Exon 20 Group, and I have been deeply influenced by the sage advice of my mentor Quint Studer whose books, especially The Calling, have transformed health care and have impacted how we operate. In that vein, Bob Hanlon and I, along with our advocacy and nursing team and our wonderful board members—from Arizona to New York—are exceedingly grateful to the physician-scientists, thoracic/medical oncologists, scientists, and molecular pathologists, as well as pharma and biotech leadership, who all play an essential role in the Exon 20 Group. Day in and day out, we would not be able to effectively assist patients and their families without this heroic group of experts who are all working to optimize survival and improve quality of life.

Horn may be reached at marcia@exon20group.org or (602) 618-0183. The Exon 20 Group encourages representation from payers and other AJMC® stakeholder groups.

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