New details from a closely watched clinical trial show that certain breast cancer patients who received the drug Trodelvy went nearly six months without their disease advancing, results which, according to some experts, could lead to a new treatment option for those whose tumors have been particularly difficult to fight.
The findings presented Saturday, at the American Society of Clinical Oncology’s annual meeting, offer a more complete picture of Trodelvy’s benefit in these hard-to-treat patients. The drug’s developer, Gilead, had claimed success in the trial a couple months ago, but didn’t offer up any specific data then.
Now, researchers are reporting that Trodelvy-treated patients lived a median five and a half months before disease progression, roughly six weeks longer than what was seen among patients who were given chemotherapy instead. This measure, known as progression-free survival, is important to how doctors and regulators think about potential new treatments for cancer.
Treatment with Trodelvy did not significantly extend study participants’ lives compared to chemo, however.
The trial compared Trodelvy against various chemotherapies in the treatment of patients with the most common form of breast cancer — called HR-positive, HER2-negative because of the proteins present on the malignant cells. Specifically, the study looked at very aggressive tumors. To enroll, participants must have had metastatic breast cancer that continued to advance even after at least one hormone therapy and at least one targeted therapy known as a CDK 4/6 inhibitor, such as Pfizer’s Ibrance.
“These were heavily pretreated patients … and trying to show benefit at that time is really challenging,” said Jennifer Litton, vice president of clinical research in the breast medical oncology department at the MD Anderson Cancer Center. “So the fact that this drug did I think is very significant.”
Litton was not involved in the study and hasn’t consulted with Gilead, although she has worked with other cancer drug developers.
Trodelvy is already approved in the U.S. to treat the rarer, faster-moving “triple negative” form of breast cancer, as well as a common type of bladder cancer. The drug was in development at the New Jersey-based biotechnology company Immunomedics, but came under Gilead’s control in 2020 through a $21 billion acquisition.
That deal, the largest in Gilead’s history, was meant to help bolster the company’s position in oncology. Despite an expensive, decade-long push to become a leader in cancer drug development, Gilead had run into several setbacks that led investors to question whether it was using money wisely. Sales from its cell therapy products, for example, grew slower than some on Wall Street had expected, and the company ultimately acknowledged overpaying in the $11 billion deal that jump-started its work there.
So far, sales from Trodelvy have been modest. They totaled $380 million last year and $146 million during the first quarter. But Gilead believes it can grow the drug into a blockbuster, with an approval in HR-positive, HER2-negative breast cancer being a key element of its strategy.
Positive data from the recent late-stage trial could help the company’s case. In March, as part of the initial announcement of the study’s success, Gilead’s chief medical officer said the plan was to assess the data and “explore potential pathways with regulatory authorities to bring Trodelvy to this group of patients.”
Yet, there remains debate about how useful the drug would be compared to currently available therapies. When the high-level results were released in March, Brian Skorney, an analyst at Baird, questioned whether Trodelvy’s potential benefits would be enough to encourage doctors to reach for it over the inexpensive chemotherapies the drug was compared against in the trial.
Gilead’s study also found no significant difference in the length of time patients in the Trodelvy group lived versus those in the chemotherapy group, with respective median overall survival of 13.9 months and 12.3 months.
To Litton, though, the data still suggest a drug like Trodelvy could have a place in treating patients with these aggressive breast cancers.
“It just gives us another tool in our toolkit. And that's always a good thing.” she said. “I don't think it will change the standard of care of what I will use [first]. I'm still going to reach for a CDK 4/6 inhibitor combination.”
“But when I get to chemotherapy,” Litton added, “this gives me another opportunity, and gives me some confidence that, even in someone who's been heavily pretreated, there's a better chance that this may provide them some disease control.”
Litton noted too that it will be important to keep following the overall survival data for Trodelvy, in addition to whether patients report feeling any better on the drug.
“If you improve someone's survival but make them so miserable that they're in a bed all day and not able to do the things they love to do, I don’t think that’s helpful,” she said.
Trial investigators plan to follow study participants for longer over time to better assess overall survival, and other measures.
In the study, 74% participants on Trodelvy and 60% of those on chemotherapy experienced an adverse event following treatment that was rated Grade 3 or higher, meaning it was serious but not immediately life-threatening.
Researchers attributed one death in the Trodelvy arm to treatment, versus none among patients who received chemotherapy. Low white blood cell counts and diarrhea were the most commonly reported adverse events.