The DESTINY-Breast09 trial, presented at the American Society of Clinical Oncology annual meeting, established trastuzumab deruxtecan plus pertuzumab as a first-line treatment option for patients with HER2-positive metastatic breast cancer.

Paolo Tarantino, MD, PhD, affiliated with Dana-Farber Cancer Institute in Boston, discussed the implications of the trial's findings. "I never liked the word 'always.' I think in oncology, very rarely the word 'always' applies and I think this is one of those cases. I don't think that the CLEOPATRA approach is dead. I think that clearly DB-09 is the most effective approach," Tarantino said.

Tarantino specified subgroups that might benefit most from the new treatment. "And so 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)]," he said. "But then there are selected patients instead that have more indolent disease, de novo, ER-positive, no visceral mets [metastases]. There, I think that giving just a few months of taxane and moving to PATINA totally makes sense. Albeit with the caveat that 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. And so I think it's something worth discussing with the patient, but remembering that we have options."

William J. Gradishar, MD, affiliated with Northwestern University Feinberg School of Medicine in Chicago, addressed the question of treatment duration. "And then the big, big question is for how long to give T-DXd/pertuzumab? And I leave this question to Bill," Tarantino said. "So 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. "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. Their duration on therapy was longer. The time until they progress was longer." "So there is an argument for pushing a little bit, not just having a finite number of cycles of therapy. So I would consider that looking at something like that in patients who don't have ER-positive disease," Gradishar added.

Hope S. Rugo, MD, a moderator affiliated with the City of Hope Comprehensive Cancer Center in Duarte, California, commented on other advancements. "So it seems like the tucatinib [Tukysa] data that was presented also I think is quite intriguing. So it seems to work in different settings. So 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 said. "So maybe we could see that delayed. And I hope with this approach, T-DXd induction and maintenance for the right patients, as Paolo pointed out, that we might cure more women with metastatic disease because we already cure a small percentage with our current approaches."