In an interview with Targeted Oncology, Pasi A. Jänne, MD, PhD, discussed the current treatment landscape for patients with EGFR-mutant lung cancer, as well as some therapies that currently are under both preclinical and clinical investigation at the Dana-Farber Cancer Institute. He shared advice for community oncologists treating this patient population.
Pasi A. Janne, MD, PhD
The Dana-Farber Cancer Institute in Boston, Massachusetts, announced that the Chen-Huang Center forEGFRMutant Lung Cancers is being established with a gift of $5 million from Winston Chen, PhD, and his wife Phyllis Huang, according to a press release. The center will help in the development of research and clinical trials, as well as improve upon the treatment of patients with EGFR-mutated lung cancer at Dana-Farber.1
“Phyllis and I hope our gift will bring much needed attention to lung cancer and illustrate how vital financial support is for making discoveries,” Chen said in a statement. “We support Pasi A. Jänne, MD, PhD, and Dana-Farber because of their impressive centers, research facilities, and the discoveries they are making every day.”
Jänne, director of the Carole M. and Phillip L. Lowe Center for Thoracic Oncology and director of the Robert and Renee Belfer Center for Applied Cancer Science at Dana-Farber, is leading health care projects and research specifically in lung cancer following the funding received from Chen and Huang’s family foundation, the Paramitas Foundation.
In 2004, Jänne and colleagues at Dana-Farber discovered the presence of theEGFR gene in lung cancer, and Dana-Farber was the first center in the United States to initiate clinical testing for these mutations. The discovery ofEGFRmutations was an important step in the development of precision medicine in lung cancer.
Over 200,000 people in the United States were diagnosed with lung cancer in 2019, and lung cancer remains the most common cause of cancer-related deaths in the country. Fifteen percent of all cases of lung cancer in the United States and the European Union areEGFR-mutant, while this subset of patients makes up 50% of all cases of lung cancer in Asia.
The establishment of the Chen-Huang Center will advance the field further with the development of new and novel clinical trials for this subset of cancers, translational studies refining treatment approaches, discovery studies looking at research models, and additional education and training opportunities related toEGFR-mutant lung cancers specifically.
“Hopefully, this will bring more attention to this disease. We can continue to focus our efforts on [EGFR-mutant lung cancers] and ultimately improve outcomes,” Jänne said. “We’ve seen the progress in the last 15 years, and there is more to go; I think we will get there.”
In an interview withTargeted Oncology,Jännediscussed the current treatment landscape for patients with EGFR-mutant lung cancer, as well as some therapies that currently are under both preclinical and clinical investigation at the Dana-Farber Cancer Institute. He shared advice for community oncologists treating this patient population.
TARGETED ONCOLOGY: Dana-Farber has announced the new Chen-Huang Center for EGFR Mutant Lung Cancers. Why is this development so important, and what do you hope to see come from this?
Jänne:Studies of EGFR-mutant lung cancer have been near and dear to our hearts for the last 15 years. We are part of the original discovery ofEGFRmutations in 2004 and had subsequently studied this both preclinically and clinically at multiple levels over the last 15 years.
The center will allow us to continue to have theEGFR-mutant lung cancer be a significant focus for our program and allow us to seamlessly take preclinical discoveries into the clinic, study what happens in patients when therapy stops working, and develop new and novel approaches for the treatment ofEGFR-mutant lung cancer. Hopefully, this will also attract new and novel clinical trials to the Dana-Farber Cancer Institute for our patients who need them when they develop resistance or run out of treatment options for theirEGFR-mutant lung cancer.
TARGETED ONCOLOGY: What are the current treatment options for patients withEGFR-mutant lung cancer?
Jänne:EGFR-mutant lung cancers make up about 15% to 20% of lung cancer in the United States and a much greater percentage of lung cancer in Asia. The current treatment for individuals with advancedEGFR-mutant lung cancer is an EGFR TKI. For the commonEGFRmutations, which include the exon 19 deletion and L858R mutation, the standard of care is osimertinib (Tagrisso). For some of the rare EGFRmutations, the standard of care is afatinib. There is also a subset of EGFRmutations that have the exon 20 insertion mutations for which we do not have an EGFR inhibitor that is currently approved, so the standard of care there would be chemotherapy.
TheEGFRmutations are not 1 disease. There are 3 main categories of disease, and there are 3 different types of treatments based on the mutation. The most common mutation is the exon 19 deletion and L858R for which osimertinib is the standard of care.
TARGETED ONCOLOGY: What does prognosis look like for patients withEGFRmutations?
Jänne:When patients develop EGFR-mutant advanced lung cancer, our therapies are not curative as is true for most other patients with advanced lung cancer. However, this is an area where we have effective therapies, such as EGFR inhibitors. Patients typically live for years with their advanced lung cancer, and they often have a very good quality of life because they are able to take an oral pill medication that does not have significant side effects.
TARGETED ONCOLOGY: What therapies are currently under development in this space?
Jänne:The biggest question at the moment is for the common EGFRmutations is how we overcome osimertinib resistance. There are severalagents that are specifically being tested, including agents like the antibody drug conjugate U3-1402 or the dual EGFRcMET bispecific antibody JNJ-372, as well as a number of combination therapies. These are most commonly combining something with osimertinib, such as a MET inhibitor like savolitinib to overcome that specific mechanism of resistance.
One of the challenges is that osimertinib resistance is not uniform. There are many ways in which 1 could become resistant, and depending on that mechanism of which the cancer develops resistance, it may be different. It may be targeting that specific resistance mechanism or having a broader approach to overcome resistance.
On the other hand, there are also efforts to enhance the initial efficacy of osimertinib, meaning can you add a second drug to osimertinib to make it work even better and improve the initial outcome. There are many studies currently underway and multiple clinical trials evaluating that. It’s still too early to know if 1 or many of those will emerge as the top, but that is the other approach, so we are not waiting for resistance but making the initial therapy better.
Over the next couple of years, we will have some clear guidance as to whether single-agent osimertinib remains as the standard of care or whether we will move into combinations. I would say for the 1 area where we do need therapies that we don’t have good therapies would be theEGFRexon 20 mutant patients. There are a number of single agents under development to see if we can find an agent like osimertinib that works with the common EGFRmutations that would work for these rare exon 20 insertion mutations.
TARGETED ONCOLOGY: Is there any research you are currently involved in at your institution?
Jänne:We are actively involved in both those areas on clinical trials, on how to overcome resistance, and studying what the mechanisms of resistance are in clinical trials to enhance the efficacy of osimertinib. For example, we are doing combination clinical trials, 1 with osimertinib and gefitinib and 1 with osimertinib and selumetinib (AZD6244), a MEK inhibitor, as a way to enhance the initial efficacy of osimertinib. We are continuing to study the biology of EGFR-mutant lung cancer preclinically and clinically. Finally, we are involved in many other trials in theEGFRexon 20 including the TAK-788 trial, which preliminarily has shown promise in the EGFRexon 20 patients and is about to start a randomized phase III clinical trial.
TARGETED ONCOLOGY: What kind of message would you like to share with community oncologists in terms of treatingEGFR-mutant lung cancers?
Jänne:There are approved therapies for EGFR-mutant lung cancers, and I think once patients develop resistance to approved therapies, that may be the time to come and visit a place like Dana-Farber Cancer Institute where we have new and novel approaches available through clinical trials to overcome resistance. If a patient wanted to explore alternatives to starting the standard of care EGFR inhibitors, a combination trial is also something we are actively involved in. If patients have a mutation for which there is no standard of care, such as the exon 20 insertions, we have clinical trials available for those patients as well.
Through clinical trials, we can develop better clinical therapies that will hopefully be approved and available to everybody. Again, this will move the treatment forward for this disease.
Dana-Farber Cancer Institute to Establish Chen-Huang Center for EGFR Mutant Lung Cancers [news release]. Boston, Massachusetts: Dana-Farber Cancer Institute; January 7, 2020. https://bit.ly/35YUQKz. Accessed January 16, 2020.