CHICAGO — The DESTINY-Breast09 trial results were presented at the American Society of Clinical Oncology annual meeting in Chicago, establishing trastuzumab deruxtecan plus pertuzumab as a new first-line treatment option for patients with HER2-positive metastatic breast cancer.

During a virtual roundtable discussion, Paolo Tarantino, a medical doctor and PhD at Dana-Farber Cancer Institute in Boston, stated, "I never liked the word 'always.'" He added, "I think in oncology, very rarely the word 'always' applies and I think this is one of those cases." Tarantino said, "I don't think that the CLEOPATRA approach is dead," but noted, "I think this clearly DB-09 is the most effective approach." He said, "If you have a patient where you can afford to use the most effective approach, young, fit patients, where you're really thinking about trying to maximize long-term outcomes, you do want to start with T-DXd/pertuzumab, particularly in high-risk scenarios, brain metastases, visceral metastases, recurrent disease, PIK3CA-mutant disease, or even patients with ER [estrogen receptor]-negative disease where we don't have the option of endocrine therapy and palbo [palbociclib (Ibrance)]."

Tarantino also identified patients for whom other strategies may apply. "There are selected patients instead that have more indolent disease, de novo, ER-positive, no visceral mets [metastases]," he said. "There, I think that giving just a few months of taxane and moving to PATINA totally makes sense." Tarantino added, "You want to tell the patient that there is another option that is more effective and we don't know if we could cure more patients with the DB-09 approach."

William J. Gradishar, a medical doctor at Northwestern University Feinberg School of Medicine, discussed potential treatment modifications for ER-positive patients. "The argument might be that obviously if they were ER-positive at some point, maybe after you got maximal response, pivoting to a PATINA-like regimen and stopping the T-DXd, give them HP [trastuzumab (Herceptin) and pertuzumab] and optimal endocrine therapy with the CDK4/6 inhibitor," Gradishar said. He cited data on response depth: "The data that was presented looking at depth of PRs [partial responses], it was interesting because if you push it, even if you didn't get a CR [complete response], but you were getting closer and closer, patients seemed to do better." Gradishar noted, "Their duration on therapy was longer," and "The time until they progress was longer." He concluded, "There is an argument for pushing a little bit, not just having a finite number of cycles of therapy." Gradishar added, "I would consider that looking at something like that in patients who don't have ER-positive disease."

Hope S. Rugo, a medical doctor at the City of Hope Comprehensive Cancer Center, commented on other data presented at the meeting. "It seems like the tucatinib [Tukysa] data that was presented also I think is quite intriguing," Rugo said. She noted, "It didn't work as well in ER-positive as in ER-negative disease, but I think you may be able to prevent, you know, one of the really hard areas of progression in patients who are on maintenance therapies is in brain." Rugo stated, "We already cure a small percentage with our current approaches," and emphasized, "There's not a one size fits all."