Yazarlar : Brian Hoyle

Yayın : DGNews

Yayın Yılı : 2014

Pubmed Linki : http://www.docguide.com/lapatinib-does-not-improve-disease-free-survival-women-her2-positive-breast-cancer?tsid=5

Konu : Tıbbi Onkoloji

Literatür İçeriği :

CHICAGO -- June 3, 2014 -- The use of lapatinib, concurrently or sequentially with trastuzumab, does not improve disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, researchers reported here at the 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO).

The disappointing findings from the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALLTO) trial were reported by Martine J. Piccart-Gebhart, MD, Université Libre de Bruxelles, Brussels, Belgium.

Trastuzumab is the post-surgical go-to drug for women with HER2-positive disease; however, about 20% of women will go on to develop a more advanced cancer within a decade. In seeking a better outcome, the researchers focused on lapatinib, an orally administered inhibitor of HER2 and epidermal growth factor receptor (EGFR) that is approved by the United States Food and Drug Administration (FDA) when used in combination with capecitabine for women with metastatic HER2-positive breast cancer following chemotherapy, and in combination with letrozole for post-menopausal women with HER2-positive disease.

ALTTO included 8,381 patients with newly diagnosed early-stage disease. Following surgery, the women were randomised to receive trastuzumab alone (n = 2,100), trastuzumab followed by lapatinib (sequential therapy, n = 2,091), or the combination of the 2 drugs (concurrent therapy, n = 2093) for 12 months.

More than half of the patients had first received adjuvant chemotherapy, and the rest were also given chemotherapy along with the clinical trial therapy. Those patients who also had hormone-positive disease also received hormonal therapies.

The study tested for superiority (P ≤ .025) between the baseline use of lapatinib plus trastuzumab and trastuzumab alone with respect to DFS. Treatment with trastuzumab followed by lapatinib was also tested for non-inferiority compared with trastuzumab alone (P ≤ .025).

At 4 years, DFS was 88% in the lapatinib plus trastuzumab arm and 86% in the trastuzumab arm (P = .048). The 4-year DFS rate for trastuzumab followed by lapatinib and for trastuzumab was 87% and 86%, respectively (P = .044). The fourth arm of the trial -- lapatinib alone -- was stopped early because of futility.

Piling on the disappointment, lapatinib offered from the beginning of treatment in combination with trastuzumab was associated with more frequent adverse events compared with trastuzumab alone: diarrhoea (75% vs 20%), rash (55% vs 20%), and hepatobiliary (23% vs 16%). In a bit of bright news, the rate of serious effects on the heart was low, with congestive heart failure occurring in <1% of women even though 95% had received an anthracycline regimen.

“Lapatinib does not add to the benefit of trastuzumab, pCR improvement did not correlate with DFS or [overall survival] benefit in this longer follow-up time assessed in the adjuvant setting,” said Edith Perez, MD, Mayo Clinic, Jacksonville, Florida. “Thus, we truly need to re-evaluate reliance on pCR as a way to evaluate new agents in early-stage HER2-positive breast cancer.”

[Presentation title: First Results From the Phase III ALTTO Trial (BIG 2-06; NCCTG [Alliance] N063D) Comparing One Year of Anti-HER2 Therapy With Lapatinib Alone (L), Trastuzumab Alone (T), Their Sequence (T→L), or their Combination (T+L) in the Adjuvant Treatment of HER2-Positive Early Breast Cancer (EBC).Abstract LBA4]

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