Dr. Bazhenova:
Hi. I'm Dr. Lyudmila Bazhenova, Professor of Medicine and Thoracic Medical Oncologist from the University of California San Diego.
Graphic: Is epidermal growth factor receptor (EGFR) mutated lung cancer more aggressive than other cancers?
Dr. Bazhenova:
Historically, patients who have an EGFR mutation do better even without receiving treatment for EGFR-targeted therapy. The reason we know that is we looked at patients with and without EGFR mutations who had tumors removed, and patients who have an EGFR mutation usually survive longer.
It's also important to know if you have an EGFR mutation because with treatment, the outcome of patients, even with stage IV disease, who have an EGFR mutation is better. So having an EGFR mutation does not mean that your cancer is more aggressive. It's actually a good prognostic, as well as a predictive biomarker if you have an EGFR mutation.
Graphic: What are EGFR-mutated lung cancer treatment options, and how does being EGFR-mutated status affect how this disease is treated?
Dr. Bazhenova:
So there are three types of EGFR mutations: sensitizing EGFR mutations, atypical EGFR mutations, and EGFR exon 20 insertions, and the treatment of those EGFR mutations differs depending on the type of mutation that you have.
In addition, we have different medications to treat EGFR mutations. We actually have, now, three generations of EGFR inhibitors. We are currently on a third-generation drug, and this is osimertinib (Tagrisso). So if you have a sensitizing EGFR mutation, the start of care would be to receive osimertinib. We have done clinical trials comparing osimertinib, which is a third-generation, as I mentioned, to erlotinib (Tarceva) and gefitinib (Iressa), which is a first-generation, and we show that osimertinib improves outcomes, improves delays, the time to progression, control of the brain, as well as overall survival.
If you have an atypical EGFR mutation – this is actually becoming a recent area of controversy because we are now separating atypical EGFR mutations into several different subtypes. For some of those subtypes, osimertinib is a good idea, and for some of those subtypes, the drug of choice is afatinib (Gilotrif). Afatinib is a second-generation EGFR inhibitor.
Then the other EGFR mutations, called EGFR exon 20 insertions, are the least common out of those three. For those patients, we do have medications approved, but it is approved in a second line. So for patients who have had chemotherapy before and then it stops working, and if you have an EGFR exon 20 insertion, then you go on an intravenous medication called amivantamab (Rybrevant), which is a bispecific monoclonal antibody against EGFR and MET.
Graphic: What are the common side effects of these treatments?
Dr. Bazhenova:
The majority of patients with EGFR mutations who receive EGFR-targeted therapy tolerate it relatively well. The main common side effect that we see is dryness of the skin. Sometimes patients can develop diarrhea and infections in the fingernail beds. You have to watch for the number of platelets, which are the small cells in the blood that control the bleeding, and we have to watch for the function of the kidneys, as well as the function of the liver. Both of them can be affected by drugs such as osimertinib.
There are rare side effects as well. It can cause inflammation of the lung, called pneumonitis, and it can cause difficulties in your heart's squeezing capacity, but those two are pretty rare. As the physicians who take care of the patients, we ask those questions, every time we see the patients, to make sure that those organs have not been affected, and we also commonly check kidney function and liver function.
Graphic: How do you determine whether someone's EGFR-mutated lung cancer is curable or not?
Dr. Bazhenova:
It depends on the stage. So patients with stage IV, unfortunately, at this point, we cannot cure those patients. Even if you have an EGFR mutation, we can treat the cancer, and the goal of treatment is to improve the symptoms, as well as to make them live longer.
For the earlier-stage disease, stages I, two, and three, patients with EGFR mutations can be cured. But the main reason why those patients are being cured is because they are being surgically operated on. So the tumor usually gets removed with surgery or gets irradiated, and the targeted EGFR drugs here are an adjunct "helper" to the "heavy lifter," if you may, which is either surgery or radiation.
Graphic: Are there clinical trials out there studying EGFR-mutated lung cancer?
Dr. Bazhenova:
For patients with newly diagnosed metastatic lung cancer with EGFR mutations, there currently are ongoing trials looking at the combination of osimertinib and bevacizumab (Alymsys, Mvasi, Avastin, and Zirabev). Bevacizumab is a drug that interferes with blood vessel production in a tumor. The hope in this study is that, maybe, we can show that adding a blood vessel drug to osimertinib improves outcomes.
A majority of work right now is on the patients who, for example, responded to EGFR-targeted therapy and did well for several months, but now, the cancer has become resistant to the EGFR drugs. There are several clinical trials being performed in that arena, with some of them using new classes of drugs called antibody-drug conjugates.
There are also clinical trials looking at bispecific antibodies against EGFR and MET, as well as bispecific antibodies against VEGF, which is a blood vessel component, as well as PD-L1. Also, there are several clinical trials, looking at the ability to improve on targeted therapy if the patient developed resistance through certain acquired mutations such as MET, or another acquired mutation, called C797S.
