While there's never a good time to be diagnosed with metastatic melanoma, former President Jimmy Carter can be thankful that he fell ill in 2015 instead of 2010.
Five years ago, it was one of those cancers "that makes oncology look bad," said Dr. Antoni Ribas, a specialist at UCLA's Jonsson Comprehensive Cancer Center. Advanced melanoma escaped the surgeon's scalpel, defied chemotherapy's poison and roared back from blasts of radiation.
"We couldn't treat it," he said.
But new remedies have begun to improve the prognosis for patients with metastatic melanoma. These treatments expose cancer cells to the full force of the immune system and target the specific genetic mutations that make it grow and spread so aggressively.
In a specialty where a meager 5% of patients once responded to available cancer drugs, combinations of new treatments now slow or stop melanoma in close to two-thirds of patients, said Anna C. Pavlick, co-director of the Melanoma Program at New York University's Langone Medical Center. Some 80% of these patients survive for at least two years.
In many cases, the new drugs can drive cancer cells into remission.
"The last five years have made a humongous difference in the outcome and survival of our melanoma patients," Pavlick said.
In fact, she said, "I'll put my nickel down: I don't think President Carter is going to die from melanoma."
Even with a tumor in his liver and four small masses on his brain, the 90-year-old humanitarian has "very limited" disease, Pavlick said. He will get stereotactic radiation to the brain — a long-standing treatment for brain metastases — and the best available drugs, she said.
Melanoma accounts for approximately 5% of all new cancer diagnoses in the United States. An estimated 76,100 Americans will be diagnosed with the disease this year, and 9,710 will die from it, according to the National Cancer Institute.
Worldwide, rates of melanoma — the deadliest of the three forms of skin cancer — are increasing faster than any other type of cancer.
It arises in the cells that make the pigment responsible for color in the skin. More than 90% of cases are linked to exposure to the sun or other sources of ultraviolet radiation.
The turnaround in treatment comes courtesy of new drugs that attack melanoma cells by a variety of means. Some unmask the cells, notorious for cloaking themselves from the immune system. Some destroy defenses that disarm the immune system's ability to fight. Others disable genes that drive growth.
Therapies that help the human immune system recognize, home in on and disrupt the normal function of cancer cells rely on monoclonal antibodies — cloned armies of genetically engineered molecules that mimic the function of immune cells.
The first such drug available to patients with melanoma that has spread beyond the skin was Yervoy, which hit the market in 2011. Two more — Keytruda and Opdivo — followed in 2014.
Meanwhile, advances in genomic medicine have led to the development of medicines that target the DNA mutations that drive cancers' growth. In melanoma, as in cancers of the breast, ovaries, prostate and lungs, scientists have discovered that therapies are often best tailored not to the organ in which the cancer occurs but to the genes that gave rise to it in the first place, or that make it thrive.
Two genetic drivers have been identified in melanoma. One is targeted by Zelboraf, which was approved by the Food and Drug Administration in 2011, and Tafinlar, which followed in 2013. Identification of a second driver spurred the development of a third targeted drug, Mekinist, which won FDA approval in 2013.
While the gene-based therapies often establish "quick control of the tumor," Pavlick said, they often stop working after 15 months. The immune-boosting drugs, by contrast, appear to continue to work for long periods.
By combining the new therapies, physicians have seen patients with advanced cases of melanoma live longer. In some patients, the cancer even seems to go away.
"It's fantastic," Pavlick said. "It's something that every oncologist wants to be part of."
Some combination therapies are still available only as part of clinical trials. They can have punishing side effects, including severe diarrhea, rashes, itching, and adrenal- and thyroid-glands problems.
Younger, more robust patients than Carter may be able to weather such a storm of side effects better. But Carter's age may not be a detriment, experts said.
"I have seen patients in this age group that respond well," Ribas said.
"It's not his age" that allowed melanoma to gain a foothold and spread, he said. "It's what's shielding his cancer from the immune system."