Game-changing lung cancer treatment may be at hand


Donna Fernandez and Dr. David Gerber

Two years ago, Donna Fernandez joined an international clinical trial at UT Southwestern evaluating nivolumab, an immunotherapy drug that had already been shown effective in treating melanoma. We wanted to observe its effects in lung cancer patients whose cancer had failed to respond to first-line therapies.

The results have been surprising. Donna’s stage 4 lung cancer is stable, and she is not alone in having that outcome.

Researchers across the U.S. and abroad compared nivolumab with the chemotherapy drug docetaxel, which is one of the most commonly used FDA-approved second-line treatments for advanced non-small cell lung cancer (NSCLC). They found that nivolumab improved overall survival and was generally well tolerated. These results are significant because options are limited for patients whose lung cancer continues to grow after their initial treatment.
So effective were the results that two months ago, on Oct. 9, the FDA approved nivolumab (brand name Opdivo) for use in treating advanced lung cancer.

Boosting natural defenses

The idea behind immunotherapy is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it puts the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer.

Donna receives an infusion once every two weeks and is generally able to return to her normal activities the following day – activities such as agility training with her dogs, gardening, taking her grandchildren on nature outings, or simply going out to eat with her husband, who has been by her side at each treatment. Donna retired from her career as an educational grant writer but has found a new role as an advocate for cancer research funding and greater cancer awareness.

Research continues to show us that all lung cancers are not the same. For example, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack.

With lung cancer, we see the greatest number of tumor mutations – and the greatest benefit from immunotherapy – among individuals with the heaviest smoking history.

This was the case for Donna, who was a daily smoker for 40 years before quitting in 2007. In 2012, she was diagnosed with stage 4 lung cancer. Donna recently told me: “No one thought I’d still be alive. I’m not just alive – I’m living life to the fullest.”

The PD-L1 connection

In addition to studying safety and efficacy, the clinical trial examined the protein biomarker PD-L1, which we think plays a role in suppressing the immune system. The study results suggest that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab. Using a biomarker helps oncologists predict which patients will do best on which treatment and plan their treatment accordingly.

According to the National Cancer Institute, lung cancer is the top cause of cancer death for both men and women. It affects more than 221,000 people in the United States each year, and the 5-year overall survival rate is only 17 percent. The percentage is far lower for metastatic lung cancer.

We are optimistic that lung cancer survival statistics will improve, in part due to immunotherapy.

This drug has the potential to be effective for a large number of lung cancer patients. The clinical trial suggests that people with lung cancer can not only live longer when treated with nivolumab, but their quality of life can be better with fewer and less severe toxicities. It will not be for everyone – in a minority of patients we saw difficult side effects – but with careful monitoring, it may be a successful step toward improving those survival statistics for many patients.