Treatment Approaches for Early Breast Cancer Progression


Paolo Tarantino, MD, explains his approach to treating patients with triple-negative breast cancer who progress early after completing adjuvant therapy.


Hope S. Rugo, MD, FASCO: This patient had an unusually long treatment-free interval, and we’re talking about all the different treatments we can give in sequence. She has HER2 [human epidermal growth factor receptor 2]–low triple-negative breast cancer, but what if she progressed sooner? That’s 1 of those disheartening situations for patients and providers, that our options seem to be more limited. If she progressed at 8 months after completing adjuvant therapy, what would you do?

Paolo Tarantino, MD: For sure, 8 months is shorter, although it would still be within the window of the KEYNOTE-355 trial, which allowed enrollment for patients who were 6 months out of treatment. Still, it reflects the fact that it would be tumor resistant to the chemotherapy received. One could use the same approach—single-agent chemotherapy—but ADCs [antibody-drug conjugates] would be even more appealing in this setting. This might be 1 of those settings where ADCs can bring benefits compared with traditional chemotherapy. Several trials are ongoing or are being planned.

I found it interesting that several antibody-drug conjugates, with the same payload as trastuzumab deruxtecan and datopotamab deruxtecan, but also the anti-HER3 ADC patritumab deruxtecan can have different adverse effects. For example, patritumab deruxtecan produces more thrombocytopenia compared with the other DXd [deruxtecan]–based ADCs. This tells us how complex these compounds are because they are both chemotherapies and targeted therapies, so the toxicity profile is related to both aspects—the toxin but also the antibody.

One thing we see with most of the DXd [deruxtecan]–based ADCs is interstitial lung disease [ILD]. That’s 1 point we need to learn, discover, and study. I believe we can somehow understand which patients are more prone to develop ILD and probably develop preventive strategies. But for the moment, with the treatment of any DXd [deruxtecan]–based ADC, T-DXd [trastuzumab deruxtecan] is the only 1 approved. It’s very important to follow the patient closely for respiratory symptoms, to educate the patient, and to monitor them radiographically to make sure there’s no suspicion of ILD. That might recommend the interruption of the treatment. Of course, treatment with steroids is the mainstay for ILD.

Transcript edited for clarity.

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