Howard “Skip” Burris III, MD, FACP, FASCO

Howard “Skip” Burris III, MD, FACP, FASCO, Chief Medical Officer and President of Clinical Operations at Sarah Cannon Cancer Center, Nashville, said the antibody-drug conjugates are especially attractive in triple-negative breast cancer. “We know chemotherapy is still effective in a large population of triple-negative breast cancer. The campothecin analog is a novel and interesting ‘payload’ for sacituzumab. Doctors are comfortable giving it, because they have given a lot of irinotecan and topo-tecan,” Dr. Burris said.

The choice of the campothecin analog is smart because it has a novel mechanism of action and is not cross-resistant with taxanes, he explained. Neuropathy—a concern with cumulative dosing—is not a problem with this drug. “There’s some degree of comfort already,” he said. Although irinotecan has never been a standard treatment in breast cancer, studies have shown some activity for it, “although not enough to make a difference,” he said.

“Now we are bringing that drug back in a different form in which it is delivered just to the cancer cells,” he said. “Now we have a novel drug that is reasonably well tolerated and shows good response rates in the third line. As it goes through the trials, it should move further forward.”

Sacituzumab govitecan joins a growing armamentarium in this breast cancer subtype. “We’re in a little bit of an odd place, where there is competition with immunotherapies,” he continued. “I think the treatment of this disease is a little unsettled, but down the road, I see the potential for combining these drugs—immunotherapies with antibody-drug conjugates and immunotherapies with chemotherapy.”

Additional Commentary

Harold Burstein, MD, PhD, FASCO, Associate Professor of Medicine at Harvard Medical School, Boston, agreed that the 30% response rate in the third-line setting was good, but he questioned whether the study’s population might have been a particularly favorable group to begin with.

Harold Burstein, MD, PhD, FASCO

“The question is whether they are really typical triple-negative patients,” he told The ASCO Post, “because lots of these patients don’t make it to the third or fourth line of treatment. That’s the reason we need to do the randomized, controlled trial that has just been opened,” which is also evaluating patients after three or more regimens. The reason for studying the drug in highly refractory patients, he suggested, is “the historical outcomes with chemotherapy in the third line are so disappointing, it’s a way to show you have really made progress.” ■

DISCLOSURE: Drs. Burris and Burstein reported no conflicts of interest.