Advanced NSCLC: Expert Talks Recent Advancements, Shortcomings

The treatment of patients with advanced non-small cell lung cancer (NSCLC) has drastically changed within recent years, thanks to the advent of targeted therapy and immunotherapy. Chemotherapy also still has a place for many patients, too, explained Heather Wakelee, MD.

Wakelee discussed the conversation she has with patients when they are first diagnosed with metastatic lung cancer. “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 not an ‘advance,’” she said in an interview with OncLive, a sister publication of Oncology Nursing News.

“We never completely move 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 they just think they don’t want it.”

Chemotherapy may not always be the optimal option, Wakelee said, though it is what she recommends for patients who require immediate treatment and are waiting for molecular testing to come back—which typically takes about 1 to 3 weeks.

After testing comes back, then the treatment team can decide if the patient should switch to a targeted therapy or immunotherapy regimen.

Targeted Therapy Advancements

Targeted therapy has been around for nearly 2 decades, and throughout that time, clinicians have always known to look out for EGFR mutations, and give patients who have them a TKI instead of chemotherapy.

Now, thanks to findings from the FLAURA trial, we know that patients with an EGFR mutation may be better off being treated with osimertinib (Tagrisso) because on average, it has a longer duration of response and improved overall survival compared with other EGFR TKIs.

“In general, for patients, [osimertinib is] better tolerated, although we do need to be mindful about cardiac and some other toxicities,” Wakelee said.

Additionally, there are 5 drugs that are FDA-approved to treat ALK-positive NSCLC, and development for other targets, including BRAF, ROS1, NTRK, RET, MET exon 14 skipping mutation, and KRAS.

“If you look, you are going to find these driver mutations in the patients’ tumors,” Wakelee said. “There are so many different medications available, [and ongoing] clinical trials for the rarer subsets so we can better understand these patients. That’s a big development.”

Immunotherapy Advancements

Immunotherapy has become a major part in treating advanced NSCLC, Wakelee said.

“Now when you go to conferences, [we discuss] immunotherapy for 2 days and then half a day on other things. That speaks to the importance of immunotherapy, and also how much we still don’t understand.”

Patients without driver mutations who express high PD-L1 stats are typically given single-agent immunotherapy, Wakelee explained. If they have a high disease burden or any level of PD-Lw with no driver mutation, they may receive immunotherapy plus chemotherapy.

“There are multiple drugs now that we have as options in that setting, and that has been really exciting.”

However, besides PD-L1, there are not great biomarkers to determine treatment, so there is still more work to be done in this space.

There are also other considerations when thinking about immunotherapy, too, including: the host, the host immunity, the microbiome, and others.

“We talk about it so much because, as much as it’s tremendously helped a good percent of patients, there’s another huge percentage of patients who are not necessarily helped with the checkpoint inhibitors,” Wakelee said. “We need to understand that better.”

A version of this article originally appeared on OncLive as, “Therapeutic Advances Promote Personalized Medicine in Advanced NSCLC.”