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Efficacy of Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy in Patients With HER2+/HR+ MBC
Dual anti-HER2 targeted therapy and chemotherapy is the current first-line standard of care for HER2 + metastatic breast cancer (MBC), with endocrine therapy (ET) the backbone of treatment in hormone receptor positive (HR +) disease. The potential ET benefit in HER2 + /HR + patients is unknown as pivotal dual anti-HER2 clinical trials precluded ET use.
Real-world data from a multi-site registry of consecutive HER2 + MBC patients treated at clinician discretion were examined. Patients that were HR + (ER + and/or PR +) and had received first-line chemotherapy alongside trastuzumab and pertuzumab were explored. Of 362 patients in the registry, 215 were excluded due to being HR- (n = 210) or not receiving chemotherapy (n = 5).
Of the 147 patients included, 91 (62%) received concurrent ET and 56 (38%) had not. Comparing the groups, there were no significant differences in age, performance status, metastatic sites, use of previous therapy and de novo metastatic disease. More patients with ER + PR + disease versus those with ER + PR- or ER-PR + received ET (73 vs 45%). The addition of ET was associated with significantly improved 5-year PFS (HR 0.58, CI 0.37-0.89, p = 0.014) and OS (HR 0.52, CI 0.31-0.90, p = 0.018), with no increase in adverse events noted.
The addition of ET to first-line dual anti-HER2 therapy post chemotherapy in patients with HER2 + /HR + MBC was associated with major gains in PFS and OS with no safety concerns evident. Further studies of this combination are justified, along with studies of how best to integrate other agents that are active in this patient subset, including CDK4/6 inhibitors.
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Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancerBreast Cancer Res Treat 2023 Feb 01;198(1)67-74, M Loft, SW Lok, R De Boer, L Malik, S Greenberg, B Yeo, A Anton, M Nottage, V Wong, L Nott, IM Collins, J Torres, F Barnett, JM Lombard, P Gibbs, L Gately
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The standard first-line therapy for patients with HER2+ metastatic breast cancer includes taxane-based chemotherapy in combination with trastuzumab and pertuzumab based on the CLEOPATRA trial, which documented significant gains in both progression-free and overall survival outcomes. In this pivotal trial, at least six cycles of chemotherapy were recommended; however, fewer cycles were allowed in case of disease progression or unmanageable toxic effects, and concurrent hormonal therapy was not allowed before disease progression. However, in routine clinical practice, hormonal therapy is commonly instituted as "maintenance therapy" in combination with trastuzumab and pertuzumab after the discontinuation of chemotherapy. This current study examined this approach via a retrospective review of real-world data and found significant improvements in progression-free and overall survival outcomes in patients who received endocrine therapy compared with those who did not. As expected, no additional safety concerns were noted with this approach.
Accumulating evidence suggests that triple-positive breast cancer should be considered a distinct entity with unique biology compared with HR−/HER2+ disease. In the early-stage setting, these tumors respond less well to neoadjuvant therapy; however, the lack of pathologic complete response (pCR) is less strongly associated with the risk of relapse. Despite lower pCR rates, patients with HR+/HER2+ disease had a better prognosis, with few disease-free survival events noted. The value of adding endocrine therapy as maintenance treatment post dual therapy with HP (trastuzumab and pertuzumab) will be evaluated in a larger randomized trial, known as the PATINA study, which is currently investigating the benefit of adding palbociclib to the core hormonal therapy plus trastuzumab and pertuzumab. The unique biology of HR+/HER2+ disease offers the opportunity to individualize treatment recommendations for these patients.