Understanding Immunotherapy and Side Effects in Advanced Lung Cancer

For patients with advanced-stage non-small cell lung cancer (NSCLC), it’s important to understand how immunotherapy works and the known side effects. An expert explained all of these key aspects during CURE®’s Educated Patient® Lung Cancer Summit.

“Treatment for advanced lung cancer has really evolved in the last two decades. Twenty years or so, the treatment used to be only chemotherapy,” explained Dr. Jyoti Malhotra, director of thoracic medical oncology at the City of Hope Orange County, at the summit. “Today, [immunotherapy] is the treatment for advanced NSCLC when a patient is diagnosed.”

How Immunotherapy Works in Lung Cancer

Before patients receive any treatment for NSCLC, Malhotra noted that it’s important for the tumor to undergo proper testing.

“Patients should have testing done on the tumor for any molecular or genomic alterations. If identified, treatment with targeted therapy is the best approach,” she said. “In patients whose tumor do not have a target identified, the approach then depends on PD-L1 expression measured in the tumor.”

PD-L1 is a type of protein that maintains the body’s immune responses, according to the National Cancer Institute. However, it may be found in abnormally high amounts on certain types of cancer cells. PD-L1 prevents T cells (immune cells) from killing cancer cells when it binds to PD-1, a type of protein found on T cells. Immune checkpoint inhibitors, a type of immunotherapy, bind to PD-L1 and block its binding from PD-1 to allow it to destroy the cancer cells.

“PD-L1 expression is a biomarker which predicts the response to immunotherapy,” Malhotra added. “If [the PD-L1 expression] is high, patients can receive treatment with immunotherapy with a PD-1 or PD-L1 inhibitor. If it’s low, then the recommended approach is a combination of chemotherapy and immunotherapy.”

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Improved Responses to Immunotherapy

In the initial trials that compared immunotherapy drugs to chemotherapy, Malhotra noted that patients demonstrated “durable responses” and continued to for years.

“So, the next step was to think if somehow immunotherapy can be combined with chemotherapy and moved into the first line setting or treatment for patients who are newly diagnosed,” she said.

The phase 3 KEYNOTE-189 trial, Malhotra further explained, was the study that evaluated this approach. Patients with NSCLC who were untreated and recently received their diagnoses were divided into two groups in the trial. The first group received the immunotherapy drug, Keytruda, plus chemotherapy, said Malhotra. In the second group, patients were treated with placebo (inactive drug) plus chemotherapy.

“The results showed a large improvement in the survival of more than 11 months when the combination of chemotherapy and immunotherapy was used,” Malhotra emphasized. “This became the new standard of care where all patients today — if they do not have a targetable mutation and are newly diagnosed — go and receive chemoimmunotherapy.”

Of note, patients who had higher PD-L1 expressions experienced a greater benefit after receiving chemoimmunotherapy, Malhotra said. Still, patients — regardless of PD-L1 expression levels — benefited from chemoimmunotherapy, she explained.

Similarly, Malhotra said that chemoimmunotherapy is standard of care for patients with small cell lung cancer (SCLC) after results from the Impower133 and CASPIAN trials.

Side Effects and Safety With Immunotherapy

Patients may also have fewer side effects when treated with immunotherapy, Malhotra noted.

“The toxicities that we see with immunotherapy are a little bit different from chemotherapy because the mechanism of action of immunotherapy is different,” she explained. “It does not cause acute or accumulative toxicities like we see with chemotherapy. The side effects from immunotherapy really happen because of an activated immune system.”

It’s important to note that having an activated immune system may “act against normal tissue,” Malhotra said, and could also cause nonspecific inflammation in organs. Side effects related to inflammation may include pneumonitis (inflammation in the lung tissue), which often comes with symptoms such as coughing or shortness of breath.

Malhotra also explained that side effects associated with an activated immune system may not be observed immediately and start to emerge around two to three months after starting treatment.

“Another thing to remember is that the immunotherapy drugs do stay in the body for quite some time,” she advised. “And even after that treatment has been stopped, the side effects from immunotherapy can manifest later or persist even after discontinuing the drug and therefore, it is important to keep that in mind.”

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