Abstract
Background: Neo-adjuvant chemotherapy (NAC) can facilitate breast conservation, allows in vivo testing of chemotherapy sensitivity and provides a route to accelerated approval of new therapies. For HER2 positive breast cancer, the anti-HER2 monoclonal antibody, trastuzumab, is a standard component of neo-adjuvant therapy.
Pertuzumab is an anti-HER2 monoclonal antibody with a distinct binding site to trastuzumab, which prevents HER2 receptor dimerisation. In early breast cancer, the addition of pertuzumab to docetaxel and trastuzumab resulted in a higher rate of pathological complete response (pCR), leading to accelerated approval in many territories. T-DM1 is a novel antibody-drug conjugate, combining trastuzumab with a potent cytotoxic, DM1, a maytansine derivative, via a stable thioether linker. In advanced breast cancer (ABC), T-DM1 improves survival compared to standard 2nd or 3rd line regimens, but not compared to first line chemotherapy plus trastuzumab. The KRISTINE trial investigated the combination of T-DM1 with pertuzumab compared to standard chemotherapy plus trastuzumab and pertuzumab in early breast cancer.
Methods: This review summarises the data supporting current standards in the neo-adjuvant treatment of HER2 positive early breast cancer and the impact of the KRISTINE trial results.
Results: T-DM1 with pertuzumab did not improve pCR over standard therapy, although the novel combination was better tolerated, and a sub-group of patients (44%) achieved pCR with the systemic chemotherapy-free regimen. This suggests that not all HER2 positive early breast cancer patients require systemic chemotherapy and provides the potential, if these patients can be identified up-front, to de-escalate therapy.
Conclusion: Although the KRISTINE trial results have not changed the standard of care for the neoadjuvant management of HER2 positive breast cancer, further research is needed to determine whether T-DM1 could be used to de-escalate NAC for selected patients.
Keywords: Breast cancer, HER2, pertuzumab, taxane, T-DM1, trastuzumab.
Graphical Abstract
Reviews on Recent Clinical Trials
Title:T-DM1 in the Neo-Adjuvant Treatment of HER2-Positive Breast Cancer: Impact of the KRISTINE (TRIO-021) Trial
Volume: 12 Issue: 3
Author(s): Alicia FC Okines*
Affiliation:
- The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ,United Kingdom
Keywords: Breast cancer, HER2, pertuzumab, taxane, T-DM1, trastuzumab.
Abstract: Background: Neo-adjuvant chemotherapy (NAC) can facilitate breast conservation, allows in vivo testing of chemotherapy sensitivity and provides a route to accelerated approval of new therapies. For HER2 positive breast cancer, the anti-HER2 monoclonal antibody, trastuzumab, is a standard component of neo-adjuvant therapy.
Pertuzumab is an anti-HER2 monoclonal antibody with a distinct binding site to trastuzumab, which prevents HER2 receptor dimerisation. In early breast cancer, the addition of pertuzumab to docetaxel and trastuzumab resulted in a higher rate of pathological complete response (pCR), leading to accelerated approval in many territories. T-DM1 is a novel antibody-drug conjugate, combining trastuzumab with a potent cytotoxic, DM1, a maytansine derivative, via a stable thioether linker. In advanced breast cancer (ABC), T-DM1 improves survival compared to standard 2nd or 3rd line regimens, but not compared to first line chemotherapy plus trastuzumab. The KRISTINE trial investigated the combination of T-DM1 with pertuzumab compared to standard chemotherapy plus trastuzumab and pertuzumab in early breast cancer.
Methods: This review summarises the data supporting current standards in the neo-adjuvant treatment of HER2 positive early breast cancer and the impact of the KRISTINE trial results.
Results: T-DM1 with pertuzumab did not improve pCR over standard therapy, although the novel combination was better tolerated, and a sub-group of patients (44%) achieved pCR with the systemic chemotherapy-free regimen. This suggests that not all HER2 positive early breast cancer patients require systemic chemotherapy and provides the potential, if these patients can be identified up-front, to de-escalate therapy.
Conclusion: Although the KRISTINE trial results have not changed the standard of care for the neoadjuvant management of HER2 positive breast cancer, further research is needed to determine whether T-DM1 could be used to de-escalate NAC for selected patients.
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Cite this article as:
Okines FC Alicia *, T-DM1 in the Neo-Adjuvant Treatment of HER2-Positive Breast Cancer: Impact of the KRISTINE (TRIO-021) Trial, Reviews on Recent Clinical Trials 2017; 12 (3) . https://dx.doi.org/10.2174/1574887112666170529094911
DOI https://dx.doi.org/10.2174/1574887112666170529094911 |
Print ISSN 1574-8871 |
Publisher Name Bentham Science Publisher |
Online ISSN 1876-1038 |
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