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Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results

Bundred, Nigel; Porta, Nuria; Brunt, Adrian Murray; Cramer, Angela; Hanby, Andrew; Shaaban, Abeer M.; Rakha, Emad A.; Armstrong, Anne; Cutress, Ramsey I.; Dodwell, David; Emson, Marie A.; Evans, Abigail; Hartup, Sue M.; Horgan, Kieran; Miller, Sarah E.; McIntosh, Stuart A.; Morden, James P.; Naik, Jay; Narayanan, Sankaran; Ooi, Jane; Skene, Anthony I.; Cameron, David A.; Bliss, Judith M.

Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results Thumbnail


Authors

Nigel Bundred

Nuria Porta

Angela Cramer

Andrew Hanby

Abeer M. Shaaban

Emad A. Rakha

Anne Armstrong

Ramsey I. Cutress

David Dodwell

Marie A. Emson

Abigail Evans

Sue M. Hartup

Kieran Horgan

Sarah E. Miller

Stuart A. McIntosh

James P. Morden

Jay Naik

Sankaran Narayanan

Jane Ooi

Anthony I. Skene

David A. Cameron

Judith M. Bliss



Abstract

PURPOSE: 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.

Journal Article Type Article
Acceptance Date Jan 20, 2022
Publication Date Apr 1, 2022
Publicly Available Date May 30, 2023
Journal Clinical Cancer Research
Print ISSN 1078-0432
Electronic ISSN 1557-3265
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 28
Issue 7
Pages 1323 - 1334
DOI https://doi.org/10.1158/1078-0432.CCR-21-3177
Publisher URL https://aacrjournals.org/clincancerres/article/28/7/1323/682200/Combined-Perioperative-Lapatinib-and-Trastuzumab

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