New options and new hope for treating lung cancer

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Credit: Michigan Medicine

Lung cancer is among the most frequently occurring forms of cancer, second only to prostate cancer in men and breast cancer in women.

It’s also the most lethal cancer type, claiming the lives of more adults than colon, breast and prostate cancer combined.

About 8 in 10 lung cancer cases are the non-small cell form of the disease.

Until recently, patients with advanced non-small cell lung cancer, known as NSCLC, had few effective treatment options. But major advances are changing the outlook for many patients.

Angel Qin, M.D., is a medical oncologist at the University of Michigan Rogel Cancer Center and an assistant professor of hematology/oncology who specializes in the treatment of lung cancer.

We asked her to walk us through the details.

It’s hard to miss all the media coverage about immune therapy and cancer. What’s all the excitement about?

Qin: In lung and other cancer types, we’re seeing very encouraging results from new immune therapies. Traditional approaches like chemotherapy and radiation attack and destroy cancer cells.

Immune therapy works with the body’s own immune system, releasing the brakes on it to defend against cancer’s spread.

The immune therapy pembrolizumab, which is called Keytruda, is receiving quite a bit of attention right now, given the results of the recent KEYNOTE-189 study.

Previously, pembrolizumab could be used in patients after they have already progressed on chemotherapy or as the first therapy for NSCLC in a select group of patients.

In KEYNOTE-189, patients were randomly divided into two groups:

The first group received the current standard of care, which is a combination of two chemotherapy drugs, and the second group received the two chemotherapy drugs plus pembrolizumab.

The results of the trial were significant.

About 70 percent of patients who received pembrolizumab along with two chemotherapy drugs were alive after one year, versus about 50 percent of patients who received the two chemotherapy drugs alone.

These results changed the standard of care for patients with nonsquamous NSCLC, who now can receive immune therapy and chemotherapy together as their first treatment.

What is known about which NSCLC patients might respond best to immune therapies?

Qin: As exciting as this development is, it’s important to acknowledge that immune therapy is not a cure, and it doesn’t work for every NSCLC patient.

The study focused only on nonsquamous NSCLC, so we do not yet know if the same benefit will be seen in patients with squamous NSCLC. More research is needed to understand what factors drive response.

One factor we believe is important is whether a protein called PD-L1 is present in a patient’s cancer. Patients whose tumors have a high level of PD-L1 are more likely to respond to immune therapy.

But we have treated patients with high PD-L1 that did not respond to immunotherapy, as well as patients with low PD-L1 that responded marvelously, so the connection is still not entirely clear.

What are the side effects of immune therapies?

Qin: Most patients tolerate immune therapy well. The most common complaint is fatigue — especially when it is combined with chemotherapy.

That’s a particularly important factor when considering the quality of life of older patients.

Because immunotherapies “supercharge” the immune system, they increase the risk that an overactive immune system will attack normal tissue.

The inflammation that results can impact any organ in the body — the thyroid, liver, lungs, GI tract and more.

So patients with certain conditions, such as autoimmune diseases like lupus or rheumatoid arthritis, aren’t candidates for immune therapy.

While severe inflammation in key organs is rare and can be life-threatening, mild to moderate inflammation-related side effects are more common and can usually be well managed with steroids.

Depending on the severity of the inflammation, patients must sometimes be taken off immune therapies in order to receive any steroid treatment, and we’re not yet sure if or when they can resume the therapy.

There is also some concern that steroid use may decrease the efficacy of immune therapy.

That’s why we always tell patients to clearly inform all of their doctors if they are receiving immune therapy, as this can affect the medications that may be prescribed.

What’s next in immune therapy for lung cancer?

Qin: Here are three important questions researchers are pursuing:

How can we improve response so it works for more patients? In the KEYNOTE-189 study, 5 in 10 patients had a positive response — that means 5 in 10 patients received no benefit or experienced a progression of disease.

We need to figure out why some patients don’t respond and if we can predict which patients are more likely to respond.

Can we use immune therapy earlier in a patient’s cancer treatment?

Pembrolizumab and other immune therapies — nivolumab (Opdivo) and atezolizumab (Tecentriq) — are approved for patients with stage 4 NSCLC.

We’re also seeing promising results from an immune therapy called durvalumab (Imfinzi) for patients with stage 3 disease who were treated with chemotherapy and radiation.

We’re looking for every opportunity to use immune therapy to interrupt the disease earlier in its progression.

Can we find other immune system pathways to target? The drugs developed to date focus on specific immune system pathways.

But it’s a complex system, and we hope to identify other pathways to target either on their own or in combination with these or other drugs. Lots of clinical trials are opening in this area.

What other lung cancer treatment advances are on the horizon?

Qin: Another exciting frontier is personalized medicine — the ability to sequence or map the genomic profile of an individual’s tumor and target its specific mutations.

Personalized medicine is a major component of the Cancer Moonshot spearheaded by former Vice President Joe Biden, and we’re beginning to see its potential in lung cancer treatment.

For instance, we’ve learned that a small percentage of lung cancers have driver mutations, which serve as green lights for the cancer to progress.

Specifically, there are approved targeted therapies for four of these mutations that act to turn off these “on switches.”

We’re seeing remarkable cancer control from these targeted therapies, which come in simple pill form.

So we do extensive tumor testing, looking at PD-L1 levels, looking for other potential markers and testing for driver mutations, all to evaluate which approach is most likely to help which patient.

These and other options for patients with every stage of lung cancer are being studied extensively in clinical trials.

The Rogel Cancer Center is participating in numerous national and cooperative group trials.

We encourage every patient to discuss clinical trial opportunities with his or her doctor to explore the possibilities.


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