Educated Patient® Lung Cancer Summit Advancements in Advanced-Stage Non-Small Cell Lung Cancer Presentation: June 25, 2022

Over the past decade, developments in the treatment of advanced-stage non-small cell lung cancer have resulted in promising long-term survival rates that were not the case years ago, according to a presenter at CURE®’s recent Educated Patient® Lung Cancer Summit.

“Until 2004 (to) 2005, the standard of care for treating advanced non-small cell lung cancer was chemotherapy,” Dr. Jyoti Malhotra, director of thoracic medical oncology at the Lennar Foundation Cancer Center at City of Hope Orange County in Irvine, California, said during her presentation. “The options were limited. And if the disease was localized, radiation could be offered with the chemotherapy. But that was it.”

During the presentation, Malhotra highlighted several advancements in the advanced-stage non-small cell lung cancer space, how those study findings have led to better outcomes and what developments may be on the horizon.

New to the Party

Although Malhotra briefly discussed targeted therapies, the bulk of her presentation focused on the swift development of immunotherapies.

“Immunotherapy is not a drug which has been around for a long time,” she said. “Most of the advances with immunotherapy have happened within the last one decade.”

Initially, she said, all Food and Drug Administration (FDA) approvals of immunotherapy agents were for patients who were already treated with a therapy, such as chemotherapy, and their disease failed to respond, or it recurred.

In this setting, various immunotherapy agents were compared with the chemotherapy docetaxel. One of the trials she highlighted focused on findings published in 2016 that showed that Tecentriq (atezolizumab) improved survival compared with docetaxel in patients with advanced non-small cell lung cancer (NSCLC) following the failure of platinum-based chemotherapy.

Six years later, there are many other advancements in this space.

“When a patient's tumor responds to immunotherapy, those responses are usually more durable and long-lasting as compared to chemotherapy,” she said.

For instance, Malhotra explained, chemotherapy typically only works for a few months and then the tumor begins growing again. However, with immunotherapy, she said, those responses may last for two years if not longer.

Using it Earlier

The question, according to Malhotra, was that if immunotherapy was proving efficacious after disease relapse, then why not try it as the primary treatment for newly diagnosed patients.

“This resulted in a number of clinical trials for newly diagnosed patients with stage 4 lung cancer in combination with chemotherapy,” she said.

One of the significant trials which showed a benefit in combining chemotherapy with immunotherapy was the phase 3 KEYNOTE-189 trial, according to Malhotra.

Here, the study results showed a significant survival benefit in patients with metastatic nonsquamous non-small cell lung cancer who received Keytruda (pembrolizumab) combined with standard chemotherapy versus chemotherapy alone. The findings led the FDA to approve the treatment regimen.

“Now chemo and immunotherapy with (Keytruda) is one of the standard-of-care regimens for newly diagnosed non-small cell lung cancer,” she said.

With the various FDA approvals of immunotherapy agents over the past few years, Malhotra noted that almost all patients with stage 4 disease are eligible to receive immunotherapy.

Benefits of Immunotherapy

Overall, she said, immunotherapy is easier to administer, is associated with less time for treatment infusions, has induced better outcomes, and is linked to a better side effect profile.

“Unlike the side effects that we see with chemotherapy, like nausea, vomiting, hair loss and infections, the side effect profile from immunotherapy is very different with the chance of a serious (side effect) happening being very low,” she explained.

Side effects as a result of immunotherapy mostly happen because they activate the immune system which acts on normal tissue that ultimately leads to inflammation, according to Malhotra. When this occurs, she noted, any organ could be affected. However, she cautioned that these side effects don’t always occur immediately following treatment.

“But there is a need to recognize them early so that treatment with steroids can be started to calm down the immune system,” she said. “For patients who are on immunotherapy, it's very important to let your care team know if you experience any symptoms at all, which are different from usual.”

Focus on Improving Efficacy

Even though immunotherapy agents have been shown to be efficacious and elicit long-term responses, that isn’t always the case.

Malhotra explained that, at best, response rates range from 50% to 60%.

Now, she said, research is focusing on ways to improve those response rates and make immunotherapy effective for more patients.

“There are a lot of clinical trials ongoing looking at different combinations either between immunotherapy/immunotherapy or immunotherapy/chemotherapy, or some of the newer novel drugs like even CAR T cells,” she said. “And we will see in the future which one of these leads to better outcomes for the patients.”

Despite some of the challenges in the space, the landscape of lung cancer has changed considerably over the years, according to Malhotra.

“With research, we hope to find more novel therapies and develop new biomarkers,” she concluded.

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