Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results
Brunt, A. M.
Shaaban, A. M.
Rakha, E. A.
Armstrong, Anne C
Cutress, R. I.
Emson, M. A.
Hartup, S. M.
Miller, S. E.
McIntosh, S. A.
Morden, J. P.
Skene, A. I.
Cameron, D. A.
Bliss, J. M.
AffiliationManchester University NHS Foundation Trust and University of Manchester, Manchester, United Kingdom. email@example.com. The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, United Kingdom. University Hospitals of North Midlands and Keele University, United Kingdom. The Christie Pathology Partnership, Manchester, United Kingdom. Leeds Institute of Medical Research at St. James's, Leeds, United Kingdom. Queen Elizabeth Hospital Birmingham and University of Birmingham, Birmingham, United Kingdom. University of Nottingham, Nottingham, United Kingdom. The Christie NHS Foundation Trust, Manchester, United Kingdom. University of Southampton and University Hospital Southampton, Southampton, United Kingdom. Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Poole Hospital NHS Foundation Trust, United Kingdom. St James's University Hospital, Leeds, United Kingdom. Queen's University Belfast, Belfast, United Kingdom. Mid Yorkshire NHS Hospitals Trust, United Kingdom. University Hospitals of North Midlands, Stoke-on-Trent, United Kingdom. Royal Bolton Hospital, Manchester, United Kingdom. University of Southampton, Southampton, United Kingdom. University of Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, Western General Hospital, Edinburgh, United Kingdom.
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AbstractBackground: EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer. Patients and Methods: This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects. Results: Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab (P = 0.007) and 1/22 (5%) control (P < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab (P = 0.02) and 2/28 (7%) control (P < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences (P = 0.002). Conclusions: Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation.
CitationBundred N, Porta N, Brunt AM, Cramer A, Hanby A, Shaaban AM, et al. Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results [Internet]. Clinical Cancer Research. American Association for Cancer Research (AACR); 2022.
JournalClin Cancer Res
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