4th Annual EGFR Resisters Summit

EGFR Resisters

New EGFR Resister-Funded Research Project with LUNGevity

EGFR Resisters and LUNGevity

Help Celebrate Lung Cancer Awareness Month in November

From EGFR Resisters

Take Action: Increase Funding to $60M in FY23 Defense Appropriations for Lung Cancer Research!

Through the Congressional Lung Cancer Caucus Chair, Representative Brendan Boyle (D-PA), GO2 Foundation for Lung Cancer submitted an appropriations request of $60M in the FY23 Defense Appropriations Bill for the Lung Cancer Research Program (LCRP).  

In recent preliminary action taken, the House Appropriations Committee has only provided $25M for lung cancer research and the Senate did not include any funding in its draft FY23 Defense Appropriations Bill for the LCRP. Please join our sponsors, Rep Boyle and Senator Jack Reed in urging House and Senate Appropriators to increase funding to $60M for the LCRP this year.  It's easy and takes a few seconds. RESEARCH=SURVIVAL!

Investigational New Drug, LP-300

Harmonic Clinical Trial

"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.

Above Paradox Valley

By Rosemerry Wahtola Trommer

You do not need to know what comes next.
There is always another storm, and you
cannot hang the tent out to dry before
it has gotten wet. You cannot shovel snow
that has yet to fall.
Put down the shovel. Breathe
into the dark spaces of your back,
feel how they open like cave doors
to let in the light.
Let your face soften. Let the creases
fall out of your brow. The mind,
no matter how clear, will never become
a crystal ball.
The wisest part of your body
knows to run when it hears
the first crashes of rock fall.
It does not pause then to consider
metamorphic or igneous,
nor does it hesitate to wonder
what might have pushed them down.
It is no small thing to trust yourself.
It’s okay to cry. It is right
that love should shake your body,
that you should find yourself trembling
in the rubble and dust
after all your certainties come down.
Your breath has not left you.
Here is the morning rain. It opens
the scent of the leaves, of the air.
All around you the world is changing.
What are you waiting for?
Here is the cup of mint tea
growing stronger in itself.
Here on this cliff of uncertainty
there is a stillness in you
so spirited, so alive
the wisest part of your body

is dancing.

Living Room Recap – Options and Next Steps If Your Lung Cancer Becomes Resistant to Your Course of Treatment

From Lung Cancer Living Room

Dr. David Gandara, professor emeritus and co-director of UC Davis Comprehensive Cancer Center’s Center for Experimental Therapeutics, discussed a number of options. The good news is that it turns out there’s a lot that can be done if your cancer becomes resistant to its current targeted therapy (TKI) or immunotherapy. He explained that the options include understanding why your lung cancer became resistant through a re-biopsy of tissue or a blood biopsy, choosing a second or third generation TKI to better treat the progression, and adding a MET inhibitor drug if the cancer shows a MET amplification. Participating in a clinical trial may also be an option.

Genomic and biological study of fusion genes as resistance mechanisms to EGFR inhibitors

From Nature Communications

The clinical significance of gene fusions detected by DNA-based next generation sequencing remains unclear as resistance mechanisms to EGFR tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer. By studying EGFR inhibitor-resistant patients treated with a combination of an EGFR inhibitor and a drug targeting the putative resistance-causing fusion oncogene, we identify patients who benefit and those who do not from this treatment approach. Through evaluation including RNA-seq of potential drug resistance-imparting fusion oncogenes in 504 patients with EGFR mutant lung cancer, we identify only a minority of them as functional, potentially capable of imparting EGFR inhibitor resistance. We further functionally validate fusion oncogenes in vitro using CRISPR-based editing of EGFR mutant cell lines and use these models to identify known and unknown drug resistance mechanisms to combination therapies. Collectively, our results partially reveal the complex nature of fusion oncogenes as potential drug resistance mechanisms and highlight approaches that can be undertaken to determine their functional significance.

Meet The Professor: Current and Future Management of Non-Small Cell Lung Cancer with an EGFR Mutation — Part 3 of a 3-Part Series

From Research to Practice

 Dr. Neil Love and Dr. Pasi Janne discuss the current and future management of EGFR+ NSCLC

Challenges With and Strategies for Tissue Procurement in NSCLC

From OncLive

Drs Benjamin Levy, Neil Morganstein, and Bhuvana Ramkumar discuss challenges of procuring for molecular testing in patients with NSCLC.

Inroads to Targeting HER2-Mutant Lung Cancer Begin Taking Shape

From OncLive

Targeted treatment options for patients with HER2-mutant non–small cell lung cancer (NSCLC) have been slow to reach benchmarks for approval given the limited patient populations harboring this disease characteristic. Three classes of agents have demonstrated efficacy in patients with HER2-mutant disease: tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and antibody-drug conjugates (ADCs).1 As the pool of available data grows for targeted treatments in this molecular subtype, investigators must stay informed about treatment options to optimize patient care, according to Edward S. Kim, MD, MBA.

“There [are] multiple alterations in HER2 we’ve found over the years,” Kim said in an OncLive® Molecular Targets Workshop. “It’s not just overexpression, we can also have gene amplification mutations. We see this in 1% to 5% of patients with lung cancer and data have showed that this is more frequent in women and never-smokers. We’re seeing more of these EGFR family mutations and most of these HER2 mutations occur in exon 20.”2 Kim is physician in chief at City of Hope Orange County and vice physician in chief at City of Hope National Medical Center, both in California.

Limited progress has been demonstrated with standard NSCLC treatments for patients such as chemotherapy and immunotherapy among patients with HER2-mutant tumors. “Chemotherapy [had] some limited degrees of efficacy [and] immunotherapies have been looked at,” Kim said. “Multiple TKIs have been developed that have a wider range of target nonspecificity.” For example, afatinib (Gilotrif) is approved for patients with NSCLC whose tumors have nonresistant EGFR mutations.3 Despite early efficacy supporting a new drug application for the pan-HER TKI poziotinib for previously treated patients with locally advanced or metastatic NSCLC with HER2 exon 20 insertion mutations, a recent meeting the FDA’s Oncologic Drugs Advisory Committee voted 9-4 that poziotinib’s benefit do not outweigh its risks.4

“We’re seeing some activity with TKIs, especially in the mutation side, but there is also activity with monoclonal antibodies such as trastuzumab [Herceptin] in combinations, and ADCs. They’ve been around for some time; however, they have been accelerating as far as the number of indications and drugs that have been coming to market,” Kim said.

Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer.

From MEDPAGE TODAY and Journal of Clinical Oncology

RESULTS: As of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months (95% CI, 2.8 to not reached). ORR for EGFR-M+ patients (n = 28) was 32.1%. Of EGFR-M+ patients, those who were c-Met high (n = 15) had an ORR of 52.6%. Median PFS was 6.8 months for non-T790M+ and for those whose T790M status was unknown, versus 3.7 months for T790M+.

Reviewing Evidence for Therapies in NSCLC With EGFR Exon 20 Insertion

From Targeted Oncology

During a Targeted Oncology case-based roundtable discussion, Zofia Piotrowska, MD, MHS, discussed the data from clinical trials supporting mobocertinib and amivantamab for patients with non–small cell lung cancer and an EGFR exon 20 insertion mutation.

The Current Landscape of Oncogene Targeted Therapies (ESMO and WCLC Recap)

From GO2 Foundation for Lung Cancer

There was a focus on treating EGFR-positive NSCLC that has progressed after being treated with currently approved EGFR targeted therapies, with several presentations of new drug combinations and new EGFR targeted therapies.

• Data from the CHRYSALIS-2 trial was presented looking at giving a combination of the new EGFR inhibitor called Lazertinib, the EGFR and MET targeted therapy Rybrevant (amivantamab)and chemotherapy to treat EGFR-positive NSCLC that had progressed after previous treatment with approved EGFR inhibitors. We saw promising results with an overall response rate of 50% including responses for patients who had their cancer spread to the brain.
• Very early phase trial data was presented where a combination treatment with the EGFR targeted therapies Tagrisso (osimertinib) and Portrazza (necitumumab) along with the HER2 inhibitor trastuzumab was used to treat EGFR-positive NSCLC that was no longer responding well to standard targeted therapies. There was initial evidence that some patients might respond to treatment and the combination will be reviewed further in a larger trial.
• Early data was presented on BBT-176, a new EGFR inhibitor that was designed to specifically work when EGFR C797X and/or T790M mutations develop – which can be ways that EGFR-positive NSCLC can become resistant to currently approved EGFR targeted therapies. Newer EGFR inhibitors that were designed to work against mechanisms of resistance are often called “4th generation EGFR inhibitors.” Responses were seen in patients with EGFR-positive lung cancer that had stopped responding to other approved EGFR targeted therapies and had one or both mutations that can be associated with EGFR targeted therapy resistance.