Therapeutic Advances Promote Personalized Medicine in Advanced NSCLC

Ellie Leick
Published: Sunday, Feb 09, 2020

Heather Wakelee, MD, professor of medicine, oncology, Stanford University

Heather Wakelee, MD

Significant research advances in targeted therapy and immunotherapy within the past few years have created a more personalized approach to treatment for patients with advanced non–small cell lung cancer (NSCLC), depending on whether they harbor driver mutations or have high PD-L1 expression, explained Heather Wakelee, MD.

“When you think about the recent advances in the setting of lung cancer, there are many of them. A lot of the things we're learning in metastatic lung cancer are brought into earlier stage disease,” said Wakelee. “There were great advances with targeted therapy with immunotherapy, but a lot [more is] to come.”

Though comprehensive molecular testing provides critical information for treatment decisions, results take around 1 to 3 weeks to arrive. For patients who require immediate treatment, there are little data to support a concrete next step. In these scenarios, Wakelee said she recommends chemotherapy, which, while not the optimal option, likely will not cause harm to the patient.

In an interview with OncLive during the 2020 Winter Lung Conference, Wakelee, a professor of medicine at Stanford University Medical Center, discussed treatment advances in advanced NSCLC and recommendations for specific clinical scenarios. 

OncLive: Could you provide an overview of the current metastatic lung cancer landscape?

Wakelee: If I have a patient coming into my office, and they have just been diagnosed, what do I do? I talk to them about the 3 pillars of therapy: chemotherapy, targeted therapy, and immunotherapy. I always talk about chemotherapy because it’s still important, though it's not an “advance.” We never completely moved away from [chemotherapy] but a lot of patients say, "Oh, I don't want it." However, they don't have a reason for saying that other than they just think they don't want it.

What are some recent advances in targeted therapy?

Many advances have happened in targeted therapy in a targeted revolution. [Targeted therapy has been around] almost been 20 years now. I don't think most people can imagine treating a patient with advanced lung cancer without knowing their driver mutations. For a while, we have known to look for EGFR [mutations] and to treat these patients with EGFR TKIs instead of chemotherapy. More recently, the FLAURA data showed us that osimertinib (Tagrisso) is perhaps a better EGFR TKI to start with because of the longer duration of response, as well as the improved overall survival compared with some of the other EGFR TKIs. In general, for the patients, [osimertinib is] better tolerated, although we do need to be mindful about cardiac and some other [toxicities].

The EGFR story set the paradigm. We have 5 drugs approved for ALK-positive NSCLC, which is really exciting. There has been faster development with many other targets. We have drugs for BRAF, ROS1, NTRK, RET, MET exon 14 skipping mutation, and now KRAS is being developed; the list can keep going. The idea is the more we look, the more we find these actionable driver mutations. When we find them, we can impact patients’ lives with many drugs. If you don't look, you don't know. If you look, you are going to find these driver mutations in the patient's tumors. There are so many different medications available, [and ongoing] clinical trials for the rarer subset so we can better understand [these patients]. That's a big development.

What are some recent advances in immunotherapy?

When I think about lung cancer education conferences—I've been doing them for a long time–and it used to be that we would spend hours debating how to best treat patients with stage III lung cancer because we didn't have much else to talk about. Then, we started just talking about EGFR and then started to talk about all the other drivers.

Now, when you go to conferences, [we discuss] immunotherapy for 2 days and then a half day on other things. That speaks to the importance of [immuno]therapy, and also how much we still don't understand. In a patient who has newly diagnosed disease, with no driver mutation, and they have high PD-L1 status, we can just give single-agent immunotherapy. If they have a high disease burden, we can give [immunotherapy] with chemotherapy if we want them to have a response [quick]. If they have any level of PD-L1 expression and no driver mutation, we know they can get chemotherapy plus immunotherapy. There are multiple drugs now that we have as options in that setting, and that has been really exciting.


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