April Salama’s War on Metastatic Melanoma

This article was written for Magnify, a Duke University School of Medicine online publication.

Fifty years since the National Cancer Act of 1971 declared “War on Cancer” and a decade since the first drug, an immunotherapy, was approved to treat metastatic melanoma, a leading clinician researcher goes head to head with melanoma brain metastasis.

At age six, April Kelly Scott Salama, MD, already knew that she wanted to be a doctor when she grew up. Somewhere there’s photo evidence of her playing in a balloon hat that’s meant to be a scrub cap.

“No one knew why I wanted to be a doctor,” said Salama, now a medical oncologist. “No one in my family was a doctor.”

But two formative experiences that she had as a teenager further solidified the calling and led her to home in on the practice and science of oncology, specifically. First, her grandfather was diagnosed with lung cancer, got better, then declined and passed away—a heartbreaking experience for Salama. At the same time, her passion for molecular biology — critical to understanding how cancer works at the cellular level — was crystallizing in AP Biology at the public school she attended in Raleigh, NC, the city where she grew up.

Salama credits great mentorship — from her high school biology teacher, her undergraduate and medical school professors at UNC Chapel Hill, and her residency and fellowship mentors at the University of Chicago — for ultimately steering her toward a career at the intersection of cancer patient care and science. After completing her fellowship in the lab of Ravi Salgia, MD, PhD, an oncologist focused on translational lung cancer research, she made it her mission to return to her native North Carolina to care for patients and continue her research.

“I felt very, very, strongly about being able to serve patients in this area,” said Salama. “I really felt I owed a debt of gratitude to the state that had educated me and set me down this path.”

But, during her job search, Salama soon learned that there were no openings for a freshly-minted lung cancer clinician-researcher at any of the state’s research hospitals. Duke, however, was looking to fill a long-vacant faculty clinician position in the Melanoma Disease Group. Surgical oncologist Doug Tyler, MD, then director of the group, was ready to train her.

Tyler’s group was investigating immune checkpoint inhibitors, which work by helping the patient’s own immune system to recognize and destroy cancer cells. The first of these immunotherapy drugs (ipilimumab) was months away from FDA approval to treat metastatic melanoma. A second one (nivolumab) was showing signs of promise, and a third one (pembrolizumab) was about to start clinical trials.

Early-stage melanoma was being treated solely with surgery, but up until that point there had never been a drug trial that improved survival in patients whose melanoma had recurred and spread to other organs. It was an exciting time for metastatic melanoma researchers, and they wanted to bring Salama into the fold.

“As division chief of medical oncology, I had the great fortune to recruit Dr. Salama from the University of Chicago, where she had distinguished herself both clinically and academically during her fellowship. While her work had been in lung cancer, I was convinced she could transition into melanoma as a clinical investigator with mentorship from Dr. Tyler, our melanoma surgeon and leader of our melanoma program in the Duke Cancer Institute (DCI) and currently at the University of Texas Medical Branch at Galveston,” said Jeffrey Crawford, MD, George Barth Geller Distinguished Professor of Immunology.

Salama consulted her mentors in Chicago and together they agreed that pivoting from lung cancer to melanoma presented an undeniably exciting opportunity for her to be on the new front lines of cancer therapy research. Salama and her husband Joseph Salama, MD, whom she’d met while at the University of Chicago, packed their bags and headed south. 

Melanoma makes up only 1% of all skin cancer cases, but it’s responsible for a large majority of skin cancer deaths, according to the American Cancer Society. That’s because melanoma is much more likely to spread to other parts of the body if not caught and treated early, unlike non-melanoma skin cancers that are unlikely to spread, highly treatable, and often curable.

“The good news is that most melanomas are actually early stage — unlike in lung cancer or pancreatic cancer where the cancer is often first discovered at an advanced stage,” Salama said. “Those early-stage melanomas are treated by our dermatologists and our surgeons and are highly curable. However, despite being completely removed, some melanomas can recur and spread. As a medical oncologist those are the patients, in particular, that I focus on trying to help with new therapies.”

In 2015, Salama was named interim director of Duke Cancer Institute’s Melanoma Disease Group. In 2017, she received a National Cancer Institute Cancer Clinical Investigator Team Leadership Award — one of only ten recipients nationally that year — which recognizes and supports outstanding mid-career clinical investigators. Executive director of Duke Cancer Institute, Michael Kastan, MD, PhD, who nominated Salama for the NCI award, said that under her leadership, the melanoma clinical trials program had received national recognition as “a leading site for patient accrual in a number of landmark melanoma trials.”

In 2018, Salama was promoted from assistant to associate professor and, after a national search for director, was named permanent director of the Melanoma Disease Group. In December 2019, the director of Duke Center for Brain and Spine Metastasis at DCI, Peter Fecci, MD, PhD, and medical director of the center Cary Anders, MD, brought Salama into the center leadership as associate medical director, said Fecci, because of her “her expertise in novel clinical trial design and her exceptional clinical care of patients with brain metastases arising from melanoma.”

Today, Salama is recognized as a leading melanoma clinician and researcher with growing expertise in melanoma brain metastasis. A physician first and foremost, she spends two days a week seeing patients in the Melanoma Clinic at Duke Cancer Center, rounds weekly at the hospital, and regularly conducts inpatient consults with melanoma brain metastasis patients.

In the 11 years since Salama began her melanoma career at Duke, the prognosis for the patients she treats — those with regionally advanced melanoma or melanoma that has spread to distant organs, including most commonly the lungs, liver, bones, and brain — has vastly improved. Before immune checkpoint inhibitors came on the market, median survival for patients with metastatic melanoma, excluding brain metastasis, noted Salama, was about nine months.

“Melanoma has become the poster child for immunotherapy,” reflected Salama. “It was the first cancer type where these immunotherapy drugs were actually beginning to work and improve survival… Now we’re at the point where median survival approaches six years. It’s just tremendous.”

Progress has been slower, however, in melanoma metastasis to the brain. A decade ago, the average life expectancy for these patients was a matter of months. With continuing advancements in surgery and stereotactic radiosurgery, and some forward movement with the newer targeted therapies and immunotherapies, the average overall survival of these patients is now more than a year.

That’s much better than it was, but it’s not good enough.

More than 50 percent of patients with metastatic melanoma will develop brain metastasis — if not at diagnosis, then at some other point — and most of these patients will be excluded from clinical trials.

“Historically, brain metastases are often life threatening and the treatments may not work quickly enough … So, this is a huge area of unmet need,” said Salama.