Big strides in treatment provide years of extra life to many advanced melanoma patients, says Mass General's Donald Lawrence, MD.

There are moments in a doctor’s life that never fade from memory. For Donald Lawrence, MD, clinical director of the Mass General Melanoma Program, one of those moments was when one of his patients married his fiancé, in the hospital, a week before he died of melanoma.

Melanoma tatoos
Tattoos in black ink signify solidarity and hope for survival of melanoma patients.

“I attended the wedding that day,” says Dr. Lawrence, who found the experience both humbling and inspiring. “I was a freshly-minted doctor,” he remembers, “with no real idea of how to help a patient near the end of life. So I decided to create an environment where he could feel safe and have his family around him.” The result was a wedding, on the hospital ward, attended by friends and family. “It was revelatory to see how people can act with tremendous grace and strength at the end of life,” he says. “It was an experience that really stayed with me.”

A New Era in Melanoma Treatment

Fast forward to 2014 and a new era in melanoma research and treatment. Dr. Lawrence now works at the leading edge of clinical research, helping to bring highly-effective drugs to patients with advanced metastatic melanoma. Dr. Lawrence is one of the honorees at Mass General’s the one hundred, an event celebrating 100 people who have dedicated themselves to making a difference in the fight against cancer. “He is the ‘go to’ melanoma doctor at Mass General,” says David Ryan, MD, chief of Hematology/Oncology at Mass General. “He is always being sought after by patients and by the MGH community.” Dr. Ryan notes that Dr. Lawrence’s work leading clinical trials has helped move the treatment of advanced melanoma forward. “There’s been a tremendous five-year run in the treatment of advanced metastatic melanoma from a time when people would routinely die within a year, to a hope of long-lasting remissions,” Dr. Ryan says.

“There’s been a tremendous five-year run in the treatment of advanced metastatic melanoma from a time when people would routinely die within a year, to a hope of long-lasting remissions.”

As Dr. Lawrence puts it, “There have been two simultaneous revolutions in the treatment of advanced melanoma.” Known as targeted therapy and immunotherapy, these two approaches are extending the lives of a significant number of people with advanced metastatic melanoma—people who, just a few years ago, would have had no effective treatment options.

Dr. Donald Lawrence, leader of clinical trial for advanced metastatic melanoma.
Dr. Donald Lawrence, leader of clinical trial for advanced metastatic melanoma.

Targeted therapy drugs shrink cancers in melanomas with the genetic mutation known as BRAF. About half of all advanced melanomas have this mutation. These medications are taken by mouth and are quite well tolerated by most people. The drawback is that after a period of success where the cancer shrinks, the  remaining resistant cancer cells may make a comeback. “That’s why we are focusing on the resistance problem in our research now,” Dr. Lawrence says. The second approach, immunotherapy, works differently. Immunotherapy stimulates the body’s own immune system to fight cancer cells. The newest generation of immunotherapy drugs, known as PD-1/PD-L1 antibodies, are available only in clinical trials such as those run by Dr. Lawrence and colleagues at Mass General and some other major medical centers, although FDA approval of at least one of these drugs is expected in the near future. The big improvement over the earlier immunotherapy drug, Interlukin-2, is that PD-1 and PD-L1 cause fewer and milder side effects and are effective in a much higher percentage of patients. “It’s truly miraculous when you see it,” Dr. Lawrence says. “I have people on these treatments who come in every two weeks for intravenous infusions. It’s like giving them water and their tumors melt away. Meanwhile they are feeling perfectly fine.” Once again, there are limitations. Only 30 percent to 40 percent of patients will have a good response, he says. But those who do respond often “get additional years out of the treatment.”  The success of cancer treatments is often measured in months.

Combination Therapy

The next chapter on melanoma treatment is already being written by Dr. Lawrence and his colleagues at the Mass General Cancer Center. Its subject: combination therapy. That means using both targeted therapy and immunotherapy drugs at the same time in the same patient. “It’s because we’re not there yet,” Dr, Lawrence says. “We’re not helping every patient yet. So we have a clinical trial going on right now combining a BRAF inhibitor with PDL-1 and with IL-2. The preliminary results look very promising.” How does it work? “We believe there is a synergy there,” he explains. “That the BRAF inhibitor, in addition to killing the melanoma cells, also makes these cells more recognizable to the immune system. This can potentially increase the effectiveness of the immunotherapy drugs.”

Patients Come First

Dr. Lawrence has come a long way from the young doctor with limited treatments and a caring attitude that led to a hospital wedding. But despite the immense progress in melanoma treatment, he says, there remain too many people with advanced melanoma who die from the disease.

“I’m primarily a clinician but I’ve found a role where I work at the intersection of science and the clinic.”

That’s why his top priority is patient care. “I’m primarily a clinician, but I’ve found a role where I work at the intersection of science and the clinic,” he says. “The science is now advancing at a tremendous pace, and I am incredibly grateful to the patients whom I’ve had the opportunity to work with in these clinical trials.” “I’ve learned to trust his judgment, wisdom and approaches,” wrote Jim Fahey, one of Dr. Lawrence’s patients.  “He has entertained my many, many questions over the years and it is so remarkable to see what he has accomplished with so many. He really has given us back our lives, and along with them, hope and inspiration.” To learn more about how you can support melanoma research, please contact us.