Alessandra Valerio was on vacation in Montreal with her family when piercing abdominal pain landed her in the emergency room. She and her husband, both doctors, suspected gastritis.
It wasn’t. An ultrasound revealed disconcerting news: a tumor mass in her pancreas and three others in her liver. At 26, she thought she had received a death sentence.
“When I saw that pancreatic tumor, I thought, ‘I’m done! I’m done!’ ” she recalls.
The following day, she, along with her husband, Jorge Perez, and 1-year-old son, Louis, returned home to Miami, where “the adventure” began, three weeks of desperate visits to doctors for a more specific diagnosis and a treatment plan. Her hope had begun to flag — one tumor alone was 10 cm — until she met Dr. Brian Slomovitz, director of gynecologic oncology at Sylvester Comprehensive Cancer Center at the University of Miami Health System.
Valerio was diagnosed with choriocarcinoma, a rare pregnancy-related cancer that forms when cells, formerly part of the placenta, turn malignant. It usually starts in the uterus and spreads to other parts of the body, as did Valerio’s.
In July 2016, Valerio began her first round of chemotherapy. A second protocol was started in September of that same year.
“I vomited every day,” she says. “It was bad, but the worst thing was that I kept thinking of my baby, how he wasn’t going to remember me.”
Chemo, explains Slomovitz, “is the first line of therapy. It works 90 to 95 percent of the time.”
Not so on Valerio. In fact, the tumor spread to her brain. Amidst the bad news, however, Slomovitz offered a nugget of information that would prove fortuitous. Testing of the tumor showed an overexpression of the protein PDL-1, and this made her a candidate for immunotherapy.
So Slomovitz began an infusion treatment of pembrolizumab, an immunotherapy drug used on cancer. This was a new, unproven treatment and there existed no prior medical reports of treating her type of chemo-resistant cancer in this way. It worked. By the second dose the tumors were gone or shrinking. “I had more energy. I could be with my baby again.”
The treatment has drawn the attention of other oncologists.
“Her response is nothing short of remarkable,” wrote Dr. Robert Coleman, another gynecologic oncologist at MD Anderson Cancer Center in Houston, who added “our recommendation would be to explore these drugs in the context of a clinical trial where both safety and efficacy can be adjudicated in the most expeditious way.”
Our immune system is made to fight off disease and infections, but it’s not always effective, for various reasons. Immunotherapy is given as a treatment to stimulate the body’s natural defense system by using chemicals produced by the body itself or with a substance created in a laboratory. Though it has been successful against other cancers, most notably with melanoma and non-small cell lung cancer, immunotherapy is still a pioneering treatment for gynecologic cancer.
An estimated 98,000 women are diagnosed annually with a gynecologic cancer in the United States, according to the American Cancer Society, and more than 30,000 will die from the disease each year. Ovarian cancer is the deadliest, accounting for 5 percent of all cancers in women, but each type has its own high risks and characteristics. Researchers hope that immunotherapy will transform treatment for some of these cancers.
“We think all [gynecologic] cancers could be good candidates” for immunotherapy, says Dr. John Diaz, a gynecologic oncologist at Baptist Health’s Miami Cancer Institute. “There’s a lot of hope to see where this goes.”
Diaz, who has participated in several clinical trials, foresees a possible future in which immunotherapy could be used alone, with two forms of immune-drugs or combined with chemotherapy as a first line of treatment for gynecologic cancers.
He and other oncologists are also keeping their eyes on research trying to develop vaccines for actual treatment of these malignancies. So far, “these vaccine trials have not panned out,” but he also points to the success of the HPV vaccine, which helps protect you against the two viruses that cause 80 percent of cervical cancer cases. (It also protects against genital warts.)
To recognize the potential of immunotherapy, it’s necessary to understand how the body’s immune system reacts to a foreign invasion — and how cancer manages to elude its attack. We produce T cells that scout out infection and disease by probing proteins on other cells.
If the signal they receive is normal, the T cell moves on. But if the proteins signal trouble, the T cell is supposed to attack the infection, or the disease, alerting the immune system to produce additional molecules — or immune checkpoints — to prevent an attack on normal tissues.
With cancer, however, the cancer cells hide from the T cells.
But researchers have discovered immunotherapy drugs that unmask this deceit — the cancer cells hiding from the T cells. The drugs block the cancerous cells from producing the proteins that hide them from the body’s immune system. Those drugs are known as immune checkpoint inhibitors and they enable the T cell warriors to do their jobs.
The drug Valerio received, pembrolizumab, is one of three checkpoint inhibitors that have received approval from the Food and Drug Administration for cancer. (The other two are ipilimumab and nivolumab.) Valerio has been cancer-free for 18 months.
Her son is now 4 years old, and she is studying to revalidate her medical license from Venezuela.
“I feel like I’m a miracle,” she says.
For Slomovitz, Diaz, and other gynecologic oncologists, immunotherapy could revolutionize the treatment of cancer. Checkpoint inhibitors are not without side effects, of course. Because immunotherapy stimulates the immune system’s reaction to disease, a patient can suffer from inflammation, rash and endocrine problems. Handled correctly, though, these are nowhere as toxic as those of chemotherapy.
“This could be a game-changer,” Slomovitz says.