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Efficacy of Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy in Patients With HER2+/HR+ MBC
TAKE-HOME MESSAGE
- This study used a real-world registry dataset to evaluate 147 patients with hormone receptor–positive and HER2-positive metastatic breast cancer (HR+/HER2+ MBC) who received first-line chemotherapy and dual anti-HER2 therapy. The efficacy of adding endocrine therapy to dual anti-HER2 therapy after discontinuation of chemotherapy was retrospectively evaluated. The investigators found that the receipt of endocrine therapy resulted in statistically significant and clinically relevant improvements in both progression-free survival and overall survival outcomes.
- The current standard practice in the first-line treatment of HR+/HER2+ MBC is to administer a CLEOPATRA trial–based regimen that includes taxane, pertuzumab, and trastuzumab until the best response is achieved and then discontinue chemotherapy. With a hazard ratio of 0.52 for overall survival with the addition of endocrine therapy, these results confirm that all patients with HR+/HER2+ MBC should receive endocrine therapy once they have achieved best response with chemotherapy.
abstract
This abstract is available on the publisher's site.
Access this abstract nowPURPOSE
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.
METHODS
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).
RESULTS
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.
CONCLUSION
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer
Breast 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 GatelyFrom 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.