FDA's Trodelvy Approval a 'Big Win' for Patients with Metastatic Triple-Negative Breast Cancer

The Food and Drug Administration’s (FDA) recent approval of the first antibody-drug conjugate to treat patients with pretreated metastatic triple-negative breast cancer (TNBC) is a major milestone, according to Dr. Aditya Bardia.

“(Trodelvy [sacituzumab govitecan-hziy]) received breakthrough designation status and received accelerated approval, which by definition tells you that it addresses a serious condition and potentially provided meaningful therapeutic benefit over existing treatments,” Bardia, a breast medical oncologist at Massachusetts General Hospital Cancer Center, said in an interview with CURE®.

The approval was made under the FDA’s Accelerated Approval Program based on results from a single-arm, multicenter phase 2 study. Continued approval may depend upon verification of clinical benefit in the confirmatory phase 3 ASCENT study, which was recently stopped early due to very promising results to review.

In the phase 2 study, Trodelvy demonstrated an objective response rate — the proportion of patients with tumor size reduction of a predefined amount— of 33.3% and a median duration of response of 7.7 months in 108 adult patients with TNBC who had previously received a median of three prior systemic therapies in the metastatic setting.

“This therapy is what we call a ‘smart bomb’, i.e. (a) targeted way of delivering the bomb precisely to the area that you'd want, said Bardia, the study’s lead investigator. “The drug has an antibody linked to a toxic payload, and thus allows a targeted way of delivering high doses of toxic therapy selectively to the cancer cells.”

Single-Arm Trial

Bardia acknowledged that because this was a single-arm study, and not a randomized trial, there is a lack of head-to-head comparisons with Trodelvy vs. chemotherapy. However, when looking at historical data in the setting, the response to standard chemotherapy has typically been between 5% to 10%, while progression-free survival is in the range of two to three months.

“While this was not a randomized trial the efficacy with this drug was approximately double of what you would expect with standard chemotherapy, based on historical data,” Bardia said.

Black Box Warning

The two most common side effects associated with the drug were diarrhea and neutropenia, which is a drop in the number of neutrophils in the blood that can lead to infection. As a result of the severe cases of diarrhea and neutropenia, Trodelvy carries a black box warning, indicating a serious safety risk.

“It is important that if the drug is used, that the side effects are managed appropriately,” Bardia said. “What you don't want is to use an efficacious agent but have to discontinue it early because of inadequate management of side effects. Early recognition and prompt management of neutropenia and diarrhea, both of which can be managed with growth factor support and anti-diarrheal medications, would be very important to ensure that the patients can derive maximum benefit from this agent.”

Bardia mentioned that most oncologists are generally comfortable with managing neutropenia and diarrhea as they are commonly encountered when treating patients. If patients are experiencing these, or any, side effects while receiving this treatment, Bardia recommended they contact their oncologist immediately to prevent things from getting worse.

Major Milestone

This approval represents a big win for patients in the management of triple negative breast cancer, according to Bardia. However, he concluded by saying more needs to be done to continue to build on the progress.

“There’s a lot more that needs to be done,” he said. “The response rate with this agent was 33%, but we need responses that go to 50, 70, and 80%. Hopefully we can significantly build on the progress and accelerate the efforts to fight this disease.”