The EGFR Resisters Have Raised Over $1 Million in Research!

EGFR Resisters

 2023 Lung Cancer Voices Summit,
March 19-21, 2023 in Washington D.C.

GO2

This three-day in-person event will empower and inspire you to make a positive difference for the millions of people living with and at risk for the lung cancer. This year, we hope to secure the requested $60 million in research funding for the Lung Cancer Research Program. First secured by GO2 in 2008, annual appropriations by Congress are required to maintain the program, a process that has been successfully shepherded each year by GO2-through our Congressional Lung Cancer Caucus and a network of advocates. If you have never participated in this effort, you will be awe-inspired. Meeting others like you and exchanging information and personal stories with your Congresspeople is an enriching and empowering experience.

Your voice is critical! We need you to help continue the momentum to increase funding for lifesaving lung cancer research. Register free today! Registration ends February 27th.

Are You on a Clinical Trial? We Need You!

From EGFR Resisters

"U.S. Clinical Trials After Osimertinib" Spreadsheet Now Available and Regularly Updated

Includes clinical trials organized by the following:  EGFR common/uncommon mutations, Exon 19 with C797X, Exon 20, MET, HER2, No new resistance mechanisms/HER3, Leptomeningeal Disease/Brain Mets, and SCLC Transformation. Updated regularly.

How Do I Handle This Cancer? Part 1
 

By Tess Taft msw, licsw ©all rights reserved

When a diagnosis of cancer lands with a thud in people's lives, treatment and uncertainty strain all the ways they know how to cope.
They and their loved ones often feel shoved off a cliff, in free fall, and emotionally shattered. Immediately lost is the assumption that the
person with cancer will die of old age. The sense of a long anticipated future disappears, and the present can feel intolerable. How do
people cope with these new, scary experiences they were never taught to expect or handle? How do their loved ones cope? What
about the children? It’s complicated. Here are some fundamental realities:

• There are different types of “copers” within each family, and
different family coping styles that are deemed acceptable by the
person with the most authority in a family or couple.

• This person’s role, often unspoken yet clearly understood within the
couple or family, determines the rules or guidelines for everyone to
follow when it comes to expressing feelings. Families can suffer if
the spoken or unspoken “rule” is this: “If you loved her(him) you
would do what I’m doing.”

• People learn to cope in healthier ways over time, as they learn how
to live with the stress of cancer in themselves or their loved one.

• Families that support each other well have learned to accept the
different styles within their group of loved ones, holding them all in
balance.

• The ways we cope define how we are trying to survive emotionally.
When it comes to cancer, past losses of loved ones who died of
cancer can determine how devastating a cancer diagnosis can feel,
even if the current prognosis is excellent. It is easy to forget the vast
advances that have occurred in cancer treatment over the last few
years and decades.

New Treatment Options for Stage IV NSCLC With Driver Alterations
 

From MEDPAGE TODAY and ASCO

The ASCO Living Guideline for advanced non-small cell lung cancer (NSCLC) with driver alterations has gotten its first update, with data from recent studies -- DESTINY-Lung01 and CodeBreaK100 -- incorporated into the guidance.

In the update, published in the Journal of Clinical Oncology, Dwight H. Owen, MD, MS, of the Ohio State University in Columbus, and colleagues recommended that for pretreated patients with advanced NSCLC and an activating HER2 (ERBB2) mutation, moving on to monotherapy with trastuzumab deruxtecan (Enhertu) is an option, per DESTINY-Lung01 findings. And in previously treated patients with advanced NSCLC and a KRAS G12C mutation, monotherapy with sotorasib (Lumakras) is on the table based on CodeBreaK100 findings.

DESTINY-Lung01 results were presented at the 2021 European Society of Medical Oncology (ESMO) meeting, while CodeBreaK100 findings were shared at the 2022 American Association for Cancer Research (AACR) meeting. Multiple experts at the time offered their take on the value of the findings via VJ Oncology.

Alexander Spira, MD, PhD, of Virginia Cancer Specialists in Fairfax: I think the most important, practice-changing data [from ESMO21] was the new and updated data on trastuzumab deruxtecan. So this is an antibody drug conjugate [ADC], and we knew about this a long time ago. It's an antibody against HER2. Previously, we saw that the drug had activity [in these patients] and that activity has borne out very nicely.

So we are seeing response rates -- very significant response rates -- in patients with HER2 mutations. Remember, it's not HER2 amplification, it's HER2 mutations. So it's practice-changing -- so please check for this mutation. You can't put people on this drug unless you check for the mutation. It's very important and we have to keep emphasizing that ... It's very exciting to have this data for 1-2% of lung cancer patients. There is a little bit of concern, however, because there is a real rate of drug-induced pneumonitis, higher than in the breast cancer population, and we need to keep that in mind, and recognize it early. 

Antibody-drug conjugates in lung cancer: dawn of a new era?

From Nature

Note: This is a deep dive into ADCs that are currently being used inside and outside clinical trials for lung cancers expressing HER2 or HER3 mutations as well as other mutations that occur after first- and second-line therapies.

Antibody-drug conjugates (ADCs) are, arguably, the fastest-growing class of oncology drugs in development, and while not a new concept, the potential to change clinical practice is vast. In lung cancer, the treatment paradigm has shifted dramatically in recent years, and now incorporates targeted therapy, immunotherapy, and systemic chemotherapy, and ADCs are now joining the list as potential options for lung cancer patients.

ADCs are unique in offering the potential to deliver highly potent cytotoxic agents to cancer cells that express a pre-defined cell surface target, thereby harnessing the powers of both cytotoxic chemotherapy and targeted therapy. Thus, ADCs are agents of precision oncology, and using these targeting properties one can greatly enhance the therapeutic index of the attached payload, compounds that would otherwise be too toxic for use. Comprising of three key components, ADCs are the “homing missiles” of modern drug development, and include (1) a monoclonal antibody that binds selectively to an antigen on the tumor cell surface, (2) a cytotoxic drug payload, and (3) a cleavable or non-cleavable linker^1,2. To date, twelve ADCs have been granted FDA approval in oncology (Table 1), and with nine of these approved since 2017, the pace of development of this class is only accelerating.

Spira Highlights Key Advancements Across the NSCLC Treatment Paradigm in 2022
 

From OncLive

In an interview with OncLive^®, Spira highlighted the top advancements across NSCLC in 2022, emphasized the need for increased genetic testing to inform treatment decisions, and previewed other agents under development.

Spira is the co-director of the Virginia Cancer Specialists Research Institute and the Phase I Trial Program, the co-chair of the US Oncology Thoracic Oncology Committee, chair of the US Oncology Research Executive Committee, a member of the US Oncology National Policy Board Executive Committee, and an assistant professor of oncology at Johns Hopkins School of Medicine in Baltimore, Maryland.
 

Another notable approval was trastuzumab deruxtecan (Enhertu) in HER2-mutant NSCLC. With has the availability of this targeted agent meant for this subset of patients?

Trastuzumab deruxtecanwas on NCCN guidelines for quite some time. Most clinicians were using it, even without an FDA approval, for at least 6 months to a year beforehand. That has been a game changer for some of those patients, as it works very well. Although the treatment does have some pulmonary toxicity, it has been a game changer for those rare HER2-mutant patients.

As targeted therapy options in NSCLC continue to expand, what are some of the challenges of choosing these agents and which patients can benefit the most?

You can't treat a patient if you don't [conduct genetic testing]. Despite this, we are sorely undertesting and we need to do more. [Testing rates] are getting better, but they are still not where they need to be. [Conducting this testing] is the most important thing. Testing will get complicated in the EGFR world, as a lot of new drugs are coming down from either clinical trials and [and approaching potential] approval. That will complicate things significantly, because you are going to have a plethora of different treatments to offer patients, and we're not going to know which is the right one [without testing].

What are physicians doing to expand access to testing?

Testing has been a challenge [in the lung cancer space]. Breast cancer doctors got this squared away years ago, where you can’t be diagnosed with breast cancer without being checked for estrogen receptor, progesterone receptor, and HER2 [status] every single time. In the lung cancer world, next-generation sequencing [NGS] has been more expensive. NGS is coming down in price, and that will certainly make it more [accessible].

However, the problem is, when it's in physicians’ hands, it never gets done. There are too many reasons why [it doesn’t get done], but we need to have metrics to force physicians to do it. I make the argument that it's better to do it too often than less often. Although we believe that NGS is an expensive test and it's going to come down in price at some point, we have no problem spending thousands of dollars a month on drugs, yet we wonder about ordering these tests to not increase the cost of medicine. The cost of doing those tests is a small fraction of what we're paying in drugs. Giving one patient an inappropriate drug will cost a lot more than [conducting NGS on everyone], even if you’re [overtesting].

Are there any agents in the pipeline that you’re excited about?

There has been some excitement around datopotamab deruxtecan [DS-1062a], which is the anti-TROP2 monoclonal antibody. They completed the randomized phase 3 [TROPION-LUNG01 trial (NCT04656652) of datopotamab deruxtecan] vs docetaxel, so we’re awaiting [data] on that. That will hopefully be in all-comers. There will be subsets looked at both in biomarker-positive and biomarker-negative patients. Now they are beginning to look at that in the frontline setting with various combinations.

Patritumab deruxtecan [U3-1402] is a HER3 drug, but it probably works by inhibiting dimerization with EGFR, or in ways we just don’t understand. There are some great data there with confirmatory randomized studies, as well as combination studies.

We are now participating in studies evaluating [EGFR] C797S [mutations]. C797S is the most common mutation that is seen, and there are some specific drugs that inhibit C797S.

Those are the most exciting things in the EGFR world, in addition to combination therapies. We recently had the approval of a [tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and platinum-based chemotherapy for adult patients with metastatic NSCLC without sensitizing EGFR mutations or ALK aberrations], though I don't know how much of a difference that's going to be in the space.

How can clinicians best remain up-to-date on developments in the NSCLC treatment space?

Keeping up his hard, [so the most important thing is] to ask questions of colleagues and other experts. The ultimate take-home message revolves around clinical trials. The second-line treatment for NSCLC, the standard of care, is still one drug: docetaxel. This chemotherapy was approved 20 years ago, and it's a terrible standard of care. It's not well tolerated in the real world, it has a lot of toxicity, and we need to be doing better. Clearly, in the second-line setting, patients should always be considered for clinical studies. [Clinical trials should also be considered] in the frontline setting and for all biomarkers.

The last 2 years have been awful with regard to clinical trials. The challenge that we had was with staffing, patients, and COVID-19. It's a different world, but we still can't lose focus that the best treatment for patients is consideration of a clinical study. Please encourage patients to participate or at least think about participating and be given the option.

Uncommon EGFR Mutations: Is There a Unicorn Among the Uncommon EGFR Mutations?
 

From Journal of Thoracic Oncology

The uncommon EGFR mutations remain a perennial challenge to treat. They constitute a heterogenous group of molecular alterations within exons 18 to 21, which include substitution mutations of G719X, L861Q, and S768I, and exon 20 insertions, with prevalence of approximately 10% to 20% of EGFR mutation-positive NSCLC. EGFR mutations are highly prevalent in East Asian populations (frequency >50%) compared with Western populations, and most data stem from studies with Asian patients. One of the major challenges in treating uncommon mutations is they are highly heterogenous with low frequencies and often missed by older assays using hotspot detection of specific exons. Nevertheless, with increased utilization of more sensitive molecular profiling assays such as next-generation sequencing (including plasma-based) and multiplex polymerase chain reaction tests in routine clinical practice, their detection rates have increased, providing opportunity for targeted treatment strategies for these patients.

Unlike the “classical” mutations comprising EGFR exon 19 deletions and exon 21 L858R substitution mutations which are well studied in landmark trials, the optimal treatment strategy for these uncommon mutations remains uncertain. Preclinical and clinical data have found greater sensitivity to second- and third-generation tyrosine kinase inhibitors (TKIs) compared with first-generation, and afatinib or osimertinib has been proposed as reasonable first-line option in this setting. Early studies with first-generation EGFR TKIs revealed variable responses and inferior outcomes, but data with afatinib reported more promising results, including a post hoc analysis from the LUX-Lung trials revealing objective response rate (ORR) of 71.1% and median progression-free survival (mPFS) of 10.7 months in the subgroup of 38 patients with major uncommon mutations (such as G719X, L861Q, and S768I). A recent pooled analysis from a large patient database from clinical trials and expanded access programs also revealed activity of afatinib against the uncommon mutations and compound mutations. On the basis of this, the Food and Drug Administration approved the use of afatinib for these rare mutations - being the sole TKI approved for this indication to date.

Uncommon EGFR Mutations: Osimertinib in Non-Small Cell Lung Cancer (NSCLC) with Atypical EGFR Activating Mutations: A Retrospective Multicenter Study
 

From Science Direct

Introduction
Epidermal growth factor receptor (EGFR) mutations drive a subset of non-small cell lung cancer (NSCLC). Patients harboring the common EGFR mutations, deletion of exon 19 (Ex19del) and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. However, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations.

Methods
Patients from six US academic cancer centers were included with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent Ex19del, L858R, or T790M mutations. Baseline clinical characteristics were collected. The primary endpoint was the time to treatment discontinuation (TTD) of osimertinib. In evaluable patients, objective response rate (ORR) by RECIST 1.1 was assessed.

Results
Fifty NSCLC patients with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n=18), G719X (28%, n=14), and Exon 20 insertion (14%, n=7). The median TTD of osimertinib was 9.7 months (95% CI, 6.5 – 12.9) overall and 10.7 months (95% CI, 3.2 – 18.1) in the first line setting (n=20). The ORR was 31.7% (95% CI, 18.1 – 48.1%) overall and 41.2% (95% CI, 18.4 – 67.1%) in the first line setting. The median TTD varied among patients with L861Q (17.2 months), G719X (7.8 months), and exon 20 insertion (1.5 months) mutations.

Conclusion
Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR activating mutation.

GO2 Foundation for Lung Cancer's Gathering HOPE Community Social Hour (Virtual), February 14, 2023 at 5-6:30 pm PT / 8-9:30 pm ET

IASLC 2023 Targeted Therapy of Lung Cancer Meeting, February 22-25, 2023, Santa Monica, CA

Hosts:  Hildy Grossman with Jordan Rich co-host
Guests:  Susan Smedley, Founder, Resilient Souls  

Anyone receiving a cancer diagnosis wonders what else they can be doing to cope that isn’t dependent on a physical protocol. Too often medical treatment overlooks the emotional component of diagnosis and treatment in facing lung cancer. Patients undergo the emotional and psychological impact of feeling walloped by their illness, often by experiencing insomnia, anxiety and depression. Our guest, Susan Smedley, was diagnosed with lung cancer when she was 32 years old. She discusses her process of transitioning from the shock of learning she had lung cancer at such an early age, with an 11-month-old child, to looking for healthy ways to cope using mindfulness, joining advocacy efforts and now creating her own organization to focus on wellness while facing trauma and challenging medical circumstances. This uplifting podcast is for everyone to help show how gravitating toward wellness efforts can significantly improve the quality of life. Listen here.