A Generalized Approach to First-Line HER2-Positive Breast Cancer Treatment


A breast cancer expert shares the current first-line standard of care for patients with HER2-positive breast cancer and presents scenarios where the standard treatment approach may not be appropriate.

Joyce O’Shaughnessy, MD: Regarding first-line therapy for metastatic HER2 positive breast cancer, we tend to biopsy that metastatic disease and to assess HER2 IC and FISH and the estrogen-progesterone receptor to really understand what disease we have to treat. In general, first-line treatment is the CLEOPATRA regimen which is a taxane plus trastuzumab and pertuzumab. Patients receive the triplet for as long as they're continuing to have reduction in tumor volume. Once they reach steady state, either having had a complete response or generally a very good partial response with some residual disease. If they're ER-negative HER2 positive, generally the chemotherapy is stopped and the patients continue on trastuzumab and pertuzumab. If they're estrogen receptor-positive, the chemotherapy is stopped. They continue the trastuzumab/pertuzumab and generally, we add endocrine therapy, either an aromatase inhibitor if they're postmenopausal or an LHRH agonist plus aromatase inhibitor if they are premenopausal. That's the general strategy for HER2-positive breast cancer in the first-line setting. If a patient had had trastuzumab and pertuzumab in the curative setting, which most patients do stage 2/3 breast cancers, node-positive disease in the adjuvant setting and preoperatively stage 2/3 breast cancers get trastuzumab and pertuzumab in the curative setting. If their disease recurred either while they were getting trastuzumab/pertuzumab or within a year of their finishing their trastuzumab and pertuzumab, so in other words, the disease is manifesting resistance to the trastuzumab and pertuzumab, that's an unusual patient but many of those patients may have also received adjuvant T-DM1. If they received preoperative pertuzumab and trastuzumab chemotherapy, had residual disease at surgery, then they would receive 10 months of T-DM1. Now if they recur pretty quickly, that patient has manifest quite a bit of resistance to standard anti-HER2-based therapy. There were not as apt to go back and use the trastuzumab and pertuzumab first line, and so we might consider the use of trastuzumab deruxtecan, for example, for those patients. Another unusual scenario would be a patient who received trastuzumab/pertuzumab in the curative setting did not receive T-DM1 for whatever reason, recurs quickly after their trastuzumab/pertuzumab. There again, we would probably use the trastuzumab deruxtecan because of the DESTINY-Breast03 trial that compared trastuzumab deruxtecan to T-DM1 and showed a very good improvement in outcome with the trastuzumab deruxtecan compared to T-DM1. That would then be the first-line choice for that unusual small group of patients, but mainly it's the CLEOPATRA regimen with taxane-trastuzumab and pertuzumab first-line.

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