Jul 11, 2012

Dual HER2 Blockade Improves Overall Survival With Metastatic Breast Cancer

NEW YORK (Reuters Health) Jul 09 – Dual HER2 blockade with trastuzumab and lapatinib extends overall survival in women with heavily pretreated HER2-positive metastatic breast cancer, researchers say.

The findings from the phase III EGF104900 study were published online June 11 in the Journal of Clinical Oncology.

A 2010 paper with preliminary data from the same trial reported that the combination improved progression-free survival (PFS) significantly compared to lapatinib alone. At that point the immature overall survival data showed a trend to improvement with combination therapy.

Dr. Kimberly L. Blackwell from Duke University Medical Center, Durham, North Carolina, and colleagues now present the trial’s final PFS and overall survival data.

In the final efficacy analysis in 291 patients, median PFS was significantly longer with combination therapy than with lapatinib (11.1 vs 8.1 weeks; p=0.011)

Median overall survival was also significantly longer with combination therapy (14 vs 9.5 months; p=0.026). The absolute overall survival rate with the combination was 10% better at six months and 15% better at 12 months than with monotherapy.

Significant factors influencing overall survival included Eastern Cooperative Oncology Group performance status, site of disease, number of metastatic sites, and time from initial diagnosis until random assignment.

Just over half of the patients enrolled in the lapatinib monotherapy arm (77/148) crossed over to combination therapy. Excluding them from a preplanned exploratory analysis resulted in a slight relative improvement in median overall survival.

In subgroup analyses, combination therapy conferred a significant survival benefit for patients with HER2-positive/estrogen receptor (ER)-negative breast cancer but not for those with HER2-positive/ER-positive breast cancer.

Women who had received up to three prior trastuzumab regimens derived a greater overall survival benefit than women who had received four or more.

Median survival after progression did not differ significantly in the combination vs lapatinib groups (10.7 vs 6.4 months; p=0.106).

Similar proportions of patients had adverse events (94% with combination therapy, 90% with monotherapy). Most adverse events with at least 10% incidence were only grade 1 or 2. The proportion with serious adverse events was larger in the combination group, however (26% vs 16%).

In summary, the authors say, “These data support the hypothesis that combining anti-HER2 agents may optimize their use.”

They note that the ongoing ALTTO study (NCT00490139) is testing sequential administration of trastuzumab followed by lapatinib, lapatinib or trastuzumab monotherapy, or lapatinib plus trastuzumab.

Eight of the 12 authors reported financial or other interests in GlaxoSmithKline, including three who are employed by the company.

SOURCE: http://bit.ly/MgUCB0

J Clin Oncol 2012.

— Reuters Health Information

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