New lung cancer treatments lead to vastly improved survival rates

UCLA Health has helped drive monumental advances in the treatment of lung cancer – increasing survival rates in the nation’s leading cause of cancer deaths.

The treatments center on immunotherapy to activate the body’s immune system to attack cancer, as well as drugs that target gene mutations fueling tumor growth. Both approaches offer first-line therapies for patients with advanced disease.

“We’ve really had two major revolutions in treatment that have happened in relatively short periods of time,” said Edward Garon, MD, director of the Signal Transduction and Therapeutics Program at the UCLA Jonsson Comprehensive Cancer Center. “This has been a very exciting time where we have started to see new therapies that are able to substantially improve outcomes for patients with lung cancer.”

In May, alone, the Food and Drug Administration approved two targeted therapies for non-small cell lung cancer, which is the most common type, based on studies led by Dr. Garon.

Deadliest cancer

Roughly 200,000 cases of lung cancer are diagnosed each year in the U.S., with up to 90% occurring in people who currently or previously smoked. Each year, more people die of lung cancer than of colon, breast and prostate cancers combined.

A report earlier this year by the American Cancer Society attributed the nation’s largest one-year drop in cancer mortality – a 2.2% decline from 2016 to 2017 – to a reduction in deaths from lung cancer. Deaths have decreased because of lower smoking rates, advances in early detection and improved treatments, the ACS said.

“The most important thing that would reduce lung cancer deaths is to have people stop – and ideally never start – smoking,” said Dr. Garon, professor of medicine at the David Geffen School of Medicine at UCLA.

Since 2013, low-dose CT screening of the lungs has been recommended for people with a history of heavy smoking. Patients should be referred to the UCLA Lung Cancer Screening Program to determine eligibility.

Dr. Garon said lung cancer is typically diagnosed at a more advanced stage than many other cancers, when the disease already has spread. While surgery for early-stage lung cancer remains the mainstay of treatment, targeted molecular therapy and immunotherapy are used for patients with inoperable cancer or metastatic disease.

Targeted therapies

Initially developed more than a decade ago, targeted drugs can block or turn off the signals that make cancer cells grow. They are designed to target cancer cells without affecting normal cells.

“In many cases, by treating patients with medications that are specifically designed for the mutations that are driving their tumor, we’ve been able to improve outcomes,” Dr. Garon said.

Dr. Garon led a study of a two-drug therapy of ramucirumab and erlotinib for EGFR (epidermal growth factor receptor) mutant non-small cell lung cancer. The therapy, approved by the FDA in May, is the first targeted combination for the roughly 10% of people with lung cancer with this mutation in the U.S.

The therapy combination works by blocking blood vessel formation along with the EGFR protein to keep cancer cells from growing.

“This is the most common mutation associated with patients who have not been smokers,” Dr. Garon said. “Patients were able to keep their disease in check for longer when they received this combination of medicines rather than when they received the single drug blocking EGFR.”

Among people with lung cancer, Asian Americans and women are more likely to have the EGFR mutation.

Also in May, the FDA approved capmatinib, the first therapy for advanced lung cancer to target abnormalities in the MET gene. The drug can be used as a front-line therapy for cancers with abnormalities in the MET gene, which comprise up to about 4% of non-small cell lung carcinoma.

“Unlike some of the newer mutations that are being found, this is a mutation that’s relatively common,” said Dr. Garon, who was one of the lead researchers.

Immunotherapy

There are several FDA-approved immunotherapies for lung cancer, which work by mobilizing the body’s own defenses to mount a stronger attack. The majority of patients with advanced disease receive immunotherapy as part of their treatment, Dr. Garon said.

In 2015, the FDA approved pembrolizumab for non-small cell lung cancer in a limited number of patients. In 2016, Dr. Garon’s research led to FDA approval for the treatment as an initial option for patients, greatly expanding access.

Last year, a UCLA study of pembrolizumab found that the five-year survival rate for patients with advanced disease went from an average of 5% in 2012 to more than 15%.

“There are a subset of patients who can be very effectively treated with these therapies that basically induce a patient’s T cells to fight against their tumor,” said Dr. Garon, who was the study’s lead author. “There have been patients who have had these tremendous responses, which has been really exciting, not just that their tumor shrinks but their life is really altered. They’re no longer feeling sick.”

DNA research

Dr. Garon said the pace of research has been accelerated by looking for tumor mutations through DNA circulating in the patient’s blood, a method far less complicated than taking a biopsy from the lungs.

“There are new mutations being found that therapies can be developed against,” he said.

Dr. Garon said he expects researchers will continue refining targeted therapies and immunotherapies, with more treatments gaining FDA approval.

“I’m hopeful we will continue to see survival rates improve,” he said. “We know that even with these advances that we’re talking about, we need better therapies. We need to increase the number of patients who benefit.”

To interview Dr. Garon, email Denise Heady at [email protected].