How Does My EGFR Mutation Affect My Treatment Approach?

The majority of patients diagnosed with non-small-cell lung cancer (NSCLC) today are tested to see if the tumor carries certain mutations, including EGFR. But not everyone will receive this testing. An important message is that if you or someone you know has a diagnosis of lung cancer, you should advocate for molecular testing. If you’re at a major cancer center that does this testing routinely, you won’t need to ask for it. But it’s important to know about molecular testing and its role in treatment decisions. Lung cancer patient advocates and advocacy groups have really been working to educate patients about its importance and to empower them to ask for this testing. So that’s the first thing. Make sure that you or a loved one with a lung cancer diagnosis has had the testing and understands what’s driving the cancer. It’s important to get that awareness out there.

EGFR-mutated lung cancer may include a variety of different mutations. The two most common are exon 19 deletions and the L858R mutation; these are both well-validated and FDA-approved therapies. There are other atypical or less common mutations, and those are still an emerging frontier. But by and large, most patients with an EGFR mutation will have one for which there’s clear FDA-approved and proven therapy.

Why Is Targeted Therapy Better Than Chemotherapy?

Targeted therapy shows increased efficacy against EGFR-mutated lung cancer. In other words, it has better anticancer activity and is relatively safe. There’s a biological advantage, too. You’re really striking at the heart of what’s causing the cancer to grow and that lock-and-key type of mechanism.

That said, this is an evolving field. There are good clinical data and approvals for combinations including targeted therapy with chemotherapy and other agents. I think what patients should know is that this should be a discussion between them and their doctor about their personal case. You can take an EGFR inhibitor or a targeted therapy alone. But there are other options, including treatment 

combinations. The reason why it’s an important conversation is that there’s a chance for increased antitumor effects against cancer [with combination treatment]. But treatment combinations come with liabilities such as greater toxicities. So it really depends on the specific case and the context.

In general, targeted medicines are taken orally. You take a pill. So, you’ll get up, take the pill, and hopefully go about your day. They often have very minimal side effects. There are some skin rashes and other things that sometimes happen; rarely, serious side effects can occur. But because they’re so tailored to the specific mutation or driver of the cancer, they spare most normal cells. As a result, you don’t get a lot of other toxicities with targeted therapy compared to chemotherapy. For the patient, it’s a minimal inconvenience. It’s much more convenient than chemotherapy, which often requires an infusion.

With any treatment, you’ll have monitoring to see if your treatment is shrinking the cancer. Your doctor will monitor you for normal liver and kidney function. Generally, we don’t see a lot of abnormalities in organ function with EGFR-targeted therapy.

What Is Oncogene Addiction?

Oncogene addiction was first defined in another setting, but it certainly applies in EGFR-mutated lung cancer. It means that cancer cells acquire a mutation that makes them grow too much. The observation that supports oncogene addiction is that, when you give a targeted therapy to a cancer with a mutation like EGFR, the cancer cells die. It means the cells really were addicted to that signal, and the cancer can’t live without it.

The molecular basis of oncogene addiction is still unclear. Many of us are exploring that. But the importance for patient treatment is that oncogene addiction is a powerful mechanism to therapeutically exploit. If you can find the oncogene and you can make a drug against it, then you can really damage the tumor.

Is Targeted Therapy a Permanent Fix?

As EGFR and other targeted therapies have gotten more potent, specific, and precise, we do see longer-term responses. But with any targeted therapy, most patients and their cancers will eventually develop resistance. That resistance occurs through a variety of mechanisms. The message for patients is that these treatments are likely to provide great benefit for a long period. However, they are unlikely to cure EGFR-mutated lung cancer. It’s an open question in the field as to how we evolve our treatments to achieve very long-term outcomes and survival, and maybe cures. For that, we’ll probably need combinations of therapies as opposed to any one targeted therapy or drug.

Is Targeted Therapy the Best Treatment Approach for Me?

There are lots of treatment opportunities, including many based on the known biology of cancer and treatment resistance. I think the important point is that, for any individual patient, it really depends on what their tumor makeup is at a given time. It’s important to understand the molecular profile, including EGFR status at diagnosis. It’s also important to analyze the tumor’s genetic makeup at resistance or progression so that you can try to tailor either a clinical trial or some other therapeutic option to a particular patient [and their cancer].

I often have patients [with EGFR-mutated cancer] ask, “Why can’t I get immunotherapy?” Immunotherapy has become ubiquitous and can be effective in lots of different lung and other cancers, and for certain subgroups of patients. It turns out that, for EGFR-mutated NSCLC, generally speaking, it hasn’t been that effective. So these other options, including EGFR-targeted therapies, are approved and more recommended. Sometimes patients will say that they want immunotherapy because that’s what someone else is receiving. So it’s useful to emphasize that if you have an EGFR mutation [for which there’s an approved treatment option], targeted therapy directed at EGFR is the preferred and proven approach.