Dataset Information

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

ABSTRACT:

Background

Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain.

Methods

In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T.

Results

Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms.

Conclusion

Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care.

SUBMITTER: Piccart-Gebhart M

PROVIDER: S-EPMC4872016 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

Piccart-Gebhart Martine M Holmes Eileen E Baselga José J de Azambuja Evandro E Dueck Amylou C AC Viale Giuseppe G Zujewski Jo Anne JA Goldhirsch Aron A Armour Alison A Pritchard Kathleen I KI McCullough Ann E AE Dolci Stella S McFadden Eleanor E Holmes Andrew P AP Tonghua Liu L Eidtmann Holger H Dinh Phuong P Di Cosimo Serena S Harbeck Nadia N Tjulandin Sergei S Im Young-Hyuck YH Huang Chiun-Sheng CS Diéras Véronique V Hillman David W DW Wolff Antonio C AC Jackisch Christian C Lang Istvan I Untch Michael M Smith Ian I Boyle Frances F Xu Binghe B Gomez Henry H Suter Thomas T Gelber Richard D RD Perez Edith A EA

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20151123 10

<h4>Background</h4>Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain.<h4>Methods</h4>In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant ...[more]

PMID: 26598744

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Dataset Information

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

Background

Methods

Results

Conclusion

Publications

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

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