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From Research to Remedy

Vanderbilt co-develops therapy for lung cancer

January 15, 2020 | Tom Wilemon

Photo by John Russell

Ishmeal Boles was so sick with cancer he was out of his mind. His lung cancer, which had gone undiagnosed, had spread to his liver, spine and brain when he was transferred from a community hospital to Vanderbilt University Medical Center.

“For three weeks, he didn’t know he was in this world; he didn’t know anyone,” said his wife, Gloria Boles.

A year later, his life is back to normal. He sings in church and plays percussion instruments, ranging from steel guitar to piano. Boles benefited from osimertinib, a targeted therapy co-developed at Vanderbilt and approved in April 2018 by the U.S Food and Drug Administration for the first-line treatment of metastatic non-small cell lung cancer with specific EGFR mutations.

“Compared to the state that I was in, it’s a total blessing that God put the people in my life to help me,” said Boles, a resident of Murfreesboro, Tennessee.

His medical case illustrates why assumptions shouldn’t be made about cancer patients. A never-smoker, he was not considered at risk for lung cancer; and as an African American, he would be less likely to have the EGFR mutation that responds to the EGFR targeted therapy. Only 5 to 7% of African Americans test positive for the mutation, but he did.

His physician, Christine Lovly, MD, PhD, associate professor of Medicine in the Division of Hematology and Oncology and co-leader of the Translational Research and Interventional Oncology Research Program at Vanderbilt-

Ingram Cancer Center, said his case illustrates the importance of personalized care.

“Working with Mr. Boles and his family has been such an inspiration,” Lovly said. “His case really emphasizes the message that everyone’s lung tumor should be tested for mutations. We should not make any assumptions about whose tumor should be tested and whose tumor should not. If a mutation is found that can be matched to a specific targeted therapy, this finding can be transformative. We also know that patients with EGFR-mutated lung cancer do not seem to benefit from immunotherapy. Tumor molecular testing is critical in order to deliver the best care to all of our patients.”

Feeling fatigued at work and often short of breath, Boles had first gone to see a doctor in February 2018. The doctor suspected heart disease, not lung cancer, and ordered cardiac tests. Boles said his heart tests didn’t indicate a problem. After his breathing issues worsened, he went back to his doctor in July 2018 and was diagnosed with stage IV lung cancer.

Suzy Crockarell of Clarksville, Tennessee, had similar symptoms in April 2019 while she was in Spain with her daughter, who was competing in the International Triathlon Union World Championships. Just being a spectator was exhausting for Crockarell, but she was thrilled that her 55-year-old daughter had a fifth-place finish in the duathlon.

“I couldn’t walk up and down hills with my daughter as I had been able to do in the past,” she said. “I was turning 82, so I figured it was old age kicking in.”

A couple of months later, she was shocked when she went to Vanderbilt for tests and was diagnosed with metastatic lung cancer.

“I’ve never been a smoker,” Crockarell said. “I live in the country, and I breathe pure air. I probably have more green plants in my house than anybody you know, so there is a constant supply of oxygen being generated. I was amazed about the diagnosis.”

She had a 10-centimeter tumor in her lung that had metastasized to her liver and lymph nodes. She also had fluid around the lungs, which made her feel quite short of breath and required a special catheter to drain. Crockarell’s tumor also tested positive for an EGFR mutation. The tumor has shrunk dramatically since she began taking osimertinib in mid-June. Before she started the medicine, she was draining more than 1 liter of fluid every few days. Now, the fluid has stopped draining, and the catheter has been removed.

She’s well enough to resume some of the chores at her home, including mowing the lawn.

“It’s a modern miracle,” Crockarell said. “I’m grateful for it.”

Targeted therapies are drugs that block the growth and spread of cancer by interfering with specific molecules involved in the progression of the disease.

“Osimertinib is a highly specific and selective drug that targets EFGR better than previous drugs that also targeted EFGR,” Lovly said. “It is more potent and has less side effects. It is stronger against the tumor and causes less damage to normal parts of the body. The development of osimertinib is a great example of how rigorous science and research can lead to better treatments for patients.”

Other targeted therapies can be prescribed for lung cancer patients with BRAF, ROS1 and ALK mutations. A study published May 26, 2019, in Journal of Clinical Oncology revealed that black patients had the lowest prevalence of all four mutations.

Lovly said more research is needed to address this disparity and to identify other lung cancer mutations that may respond to targeted therapies.

“We have to do tumor molecular testing and we have to do it for everybody without any bias or assumptions,” she said.