A New Era of Hope in Lung Cancer

As immunotherapy revolutionizes lung cancer treatment, scientists are considering how to make it work for more of those affected by the disease.
BY MELANIE PADGETT POWERS
PUBLISHED: APRIL 18, 2016
Pam Griffith’s days were filled with sunshine, golf and trip planning. She and her husband, Randy, were basking in retired life, living on Royal Lakes Golf Course in Lakewood Ranch, Florida. So when a nagging cough would not disappear, she blamed it on seasonal allergies and tried to ignore it. After all, she was too busy to go to the doctor: She played golf three to four days a week with friends and other couples, and she and Randy had just returned from one of their many trips, their first river cruise, down the Rhine River in Germany. “I didn’t want anything to interrupt our lifestyle, so I didn’t make time for that until I
PHOTO COURTESY OF PAM GRIFFITH
PHOTO COURTESY OF PAM GRIFFITH
had to,” says Griffith, age 67. “We don’t stay in the house, and we don’t sit around.”

But after six months of the persistent cough, she mentioned it to her family doctor, who referred her to a pulmonologist. A CT scan revealed a mass in the lower right lobe of her right lung in March 2013. After surgery to remove the lobe and the tumor, she was diagnosed with adenocarcinoma with sarcomatoid cells, a rare combination of non-small cell lung cancer (NSCLC) characteristics that, in the past, have been associated with a relatively poor prognosis because these tumors are resistant to some types of chemotherapy. Griffith began chemotherapy with cisplatin and etoposide, plus radiation, five days a week for seven weeks.

Not only did the treatment cause severe nausea, which led to dehydration, but the cancer began to rapidly spread throughout her body. Visible signs began to pop up: a lesion on the back of her head, a bump on her left shoulder blade, a bulge on the right side of her neck. The chemotherapy wasn’t working, so she and her husband decided to switch from the local oncologist to a large academic cancer center. They turned to Scott J. Antonia, chair of the Thoracic Oncology Department at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida.

In her first visit to Antonia, after a CT scan, he “gave us some news that was absolutely devastating,” Griffith says. “He turned to us and he said, ‘We can no longer hope to cure you.’ And that was shocking. My entire body just went numb. My mind was racing, but I couldn’t move.”

But Antonia did offer the Griffiths a ray of hope: an immunotherapy clinical trial. In September 2013, Griffith enrolled in phase 3 of the CheckMate 057 trial and began to receive the drug Opdivo (nivolumab) every other Wednesday. Just as she had been able to see the cancer bumps growing on her body, she soon was able to watch them shrink. Eventually, there was no sign of cancer. She stayed on Opdivo for almost two years, until August 2015, when she began having joint pain, thought to be a side effect of the drug. She continues to receive a CT scan every three months, but the cancer has stayed away. “The cancer I had was a death sentence,” she says, “but now it’s a whole different ball game, because people are surviving, and the doctors are learning as we all go along.”

A NEW ERA

Immunotherapy is revolutionizing lung cancer treatment, ushering in a new era of hope for those with a disease that is the leading cause of cancer-related death in the United States in both men and women, killing more people every year than breast, prostate and colon cancers combined. It was expected that about 221,000 cases of lung cancer would be diagnosed in 2015, with more than 80 percent of those occurring in patients over age 60.

NSCLC is the most common form of lung cancer, accounting for approximately 85 percent of cases. Small cell accounts for the other 15 percent. There are two main types of NSCLC: squamous cell and the more common nonsquamous cell, which is primarily adenocarcinoma.

Small cell lung cancer, which tends to progress quickly, is usually treated with chemotherapy and radiation, often palliatively, with most patients relapsing in just a few months. In the NSCLC realm, stages 1 and 2 disease can usually be treated first with surgery to remove the tumors, sometimes followed by chemotherapy and/ or radiation. However, because lung cancer often isn’t symptomatic until stages 3 or 4, the majority of people are diagnosed in later stages, when surgery is usually not an option because the cancer has spread throughout the body. In 40 percent of NSCLC cases, the cancer is diagnosed in stage 4; in this stage, fewer than half of patients live a year, and only 10 percent survive two years.

Immunotherapy is typically used only in stage 4 NSCLC, and the most promising type so far has been checkpoint inhibitors. In 2015, one such drug, Opdivo, the therapy that helped Griffith, became the first immunotherapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of lung cancer. Opdivo is approved for metastatic squamous or non-squamous NSCLC and has also been approved to treat the skin cancer melanoma. In NSCLC, the FDA has approved a second checkpoint inhibitor, Keytruda (pembrolizumab), only for patients whose tumors express the protein PD-L1. Both drugs are currently approved only as second-line therapies, to be tried after chemotherapy has stopped working.



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