TYKERB (lapatinib ditosylate) - Updated Information on Efficacy (Health Canada)

HER-2 Breast Cancer http://goo.gl/LwBZB (Photo credit: TipsTimes)

TYKERB (lapatinib ditosylate) - Updated Information on Efficacy - For Health Professionals - Recalls & alerts - Healthy Canadians Website: 

Note that this was previously highlighted in June of 2012 at ASCO in Chicago:

"In his discussion, Gunter von Minckwitz, MD, PhD, of the German Breast Group and the University of Frankfurt, Germany, said there is increasing evidence that lapatinib is not as active as trastuzumab in a number of breast cancer therapy settings, perhaps because of the rapid development of secondary resistance and because dual blockade appears to be the most promising approach for the future."

It often takes time, but Health Canada has now made notice of updated prescribing information.

Excerpt from Health Canada update via GlaxoSmithKline Inc:

"Subject: Updated Information on Efficacy - TYKERB® (lapatinib ditosylate)-based regimens are less effective than HERCEPTIN®(trastuzumab)-based regimens in certain settings:

Based on the results of preplanned interim analyses of two studies, GlaxoSmithKline would like to advise you of the following:

• In patients with HER2+ metastatic breast cancer who have not received prior trastuzumab, comparative data have shown that lapatinib-based regimens are less effective than trastuzumab based treatment regimens.

• Prescribers are reminded that TYKERB^® should not be prescribed in combination with capecitabine unless patients have progressed on prior trastuzumab therapy in the metastatic setting.

• GlaxoSmithKline has updated the TYKERB^® Product Monograph to include a statement that lapatinib-based regimens are less effective than trastuzumab-based regimens in certain settings.

CEREBEL(EGF111438) (N=540) is a randomised Phase III study comparing the effect of  lapatinib in combination with capecitabine relative to trastuzumab in combination with capecitabine on the incidence of CNS as site of first relapse in women with HER2 positive metastatic breast cancer. Patients were stratified based on prior trastuzumab treatment (yes versus no) and number of prior treatments for metastatic disease (0 versus ≥1 line). The study was stopped early due to results of a pre-planned interim analysis (N=475). There was superior efficacy with the trastuzumab plus capecitabine combination in terms of progression-free survival (PFS) and overall survival (OS) compared to the lapatinib plus capecitabine combination. Median PFS was 6.60 months in the lapatinib-containing arm compared with 8.05 months in the trastuzumab-containing arm (HR=1.30; 95%CI 1.04 to 1.64).  The median OS was 22.7 months in the lapatinib-containing arm compared with 27.3 months in the trastuzumab-containing arm (HR=1.34 (95%CI 0.95 to 1.90).

COMPLETE is a randomised Phase III study (EGF108919) (N=636) comparing the activity of lapatinib plus taxane followed by lapatinib alone versus trastuzumab plus taxane followed by trastuzumab alone as first line therapy for women with HER2 positive metastatic breast cancer. The study was stopped early due to superior efficacy of the trastuzumab plus taxane combination in terms of progression-free survival.  Results from a pre-planned interim analysis showed that  the PFS in the lapatinib-containing arm was lower than in the trastuzumab-containing arm (median PFS was 8.8 months in the lapatinib-containing arm compared with 11.4 months in the trastuzumab-containing arm; HR=1.33; 95% CI 1.06 to 1.67, p=0.01).  The hazard ratio for OS was 1.1 (95% CI 0.75 to 1.61; p=0.62), based on 18% (n=115) deaths."

The revised Product Monograph for TYKERB^® may be accessed on the Health Canada Website or on the Canadian Website of GlaxoSmithKline.

*Click here for link to full Health Canada release information.

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