Frances Shepherd, MD
When Frances A. Shepherd, MD, FRCPC, first took an interest in lung cancer, the standard treatment for localized disease was to cut out the tumor and hope for the best, while the standard treatment for metastatic disease was to prescribe pain medication and send the patients home to die.
Shepherd has spent more than 3 decades demonstrating that medical oncology can help patients with lung cancer during all stages of their journey. She worked on some of the earliest clinical trials to prove the value of chemotherapy in metastasized disease and then led studies that demonstrated the curative potential of chemotherapy after complete resection and the efficacy of molecularly targeted agents such as erlotinib (Tarceva).
Her commitment to clinical trials research led Shepherd to become the chair of the Lung Cancer Committee of the National Cancer Institute of Canada Clinical Trials Group (now the Canadian Clinical Trials Group), a post that gave her a voice in every lung cancer trial for 19 years and helped make the country into a center of lung cancer research.
“I had no real ambition to do clinical trials during medical school or immediately thereafter, but then I took part in my first Lung Cancer Study Group trials and all my plans changed,” Shepherd said. “Once you are bitten by that trial bug—once you realize that you can do work that improves treatment for everyone—you never want to do anything else.”
Shepherd received her medical degree from the University of Toronto in 1970, went to Montreal for her internal medicine residency at Royal Victoria Hospital, and soon decided she wanted to specialize in cancer treatment. This was an unusual decision for a promising young doctor in the 1970s because oncology was only a fledgling specialty at the time. It still lacked both the recognition of the medical establishment and a formal training program in Canada.
Cancer treatment was improving rapidly, though, and Shepherd sensed an opportunity to do interesting and important work. When the University of Toronto launched its program to train medical oncologists, she was one of the first to sign up.
Designing Influential Trials
The decision to specialize in lung cancer was, at that time, less calculated. Toronto General (now University Health Network, a large universityaffiliated hospital complex that includes Princess Margaret Cancer Centre and has been Shepherd’s base since 1975) had one of the premier thoracic surgery units in North America. Surgeons at the hospital, along with medical and radiation oncologists and lung cancer pathologists, were among the founding members of the North American Lung Cancer Study Group. It was through this Clinical Cooperative Research Group that Shepherd was introduced to clinical trials. In the nearly 4 decades that have followed, Shepherd has participated in more than 100 clinical trials, and she has led many of the most influential among them.
The JBR.10 North American Intergroup trial, for example, made chemotherapy after complete surgical resection a new global standard of care for patients with stage IB or II non–small cell lung cancer (NSCLC). Shepherd and her colleagues randomized 482 patients who had undergone surgery to either observation or treatment with vinorelbine plus cisplatin. On average, patients who received the chemotherapy lived significantly longer (94 vs 73 months; HR for death during the study period, 0.69; P = .04). They also had a higher 5-year survival rate (69% vs 54%; P
“That was a critical trial for several reasons,” Shepherd said. “We did not simply find that chemotherapy extends life for a few months or years—although it certainly did that for many patients—we also found that it increased the cure rate. The chemotherapy was effective enough in a significant percentage of patients to destroy undetected microscopic cancer cells. Those are people who otherwise would have suffered recurrence and death, but instead had the chance to live healthy lives. That is a rare victory, indeed, in the world of lung cancer, and it was very gratifying.”
Another important aspect of the JBR.10 trial was the unprecedented decision to collect and save tissue samples from patients who took part; in fact, the trial was the first lung cancer trial ever to stratify by an oncogene driver. Shepherd and her colleagues established a trial-associated tissue bank.
Time has borne out Shepherd’s intuition; sample collection has become increasingly common over the past 2 decades, and now almost all large trials set up tumor banks. Furthermore, samples from this bank established more than 20 years ago are still being evaluated in collaboration with researchers in Canada, the United States, and Europe.