Women with persistent and aggressive breast cancer could significantly extend their remaining lifespan by taking GlaxoSmithKline’s Tykerb (lapatinib) in combination with injectable rival Herceptin (trastuzumab, Roche), new trial data suggest.

In a Phase III clinical study presented by GSK at the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium in Texas, US, patients with trastuzumab-resistant breast cancer achieved a median overall survival of 14 months on Tykerb and Herceptin combined, compared with a median 9.5 months on Tykerb alone.

The 296 women enrolled in the trial had HER2-positive breast cancer – characterised by over-expression of the HER2 protein in cancer cells – and had experienced recurrence of breast cancer despite having received a median of three prior trastuzumab-based therapies.

Patients were randomised to either monotherapy with lapatinib 1,500mg daily or to a combination of lapatinib 1,000mg per day, administered orally, and trastuzumab 2mg/kg. Crossover to combination therapy was permitted if the breast cancer progressed after at least four weeks of therapy, suggesting that the real benefits of the combination regimen were understated. Of the women on lapatinib monotherapy, 52% (77 out of 148) crossed over to the combination arm.

The updated survival analysis showed that at the data cut-off point for overall survival (OS), 218 deaths (74% of the total) had occurred overall. Median OS following treatment with Tykerb plus Herceptin was 60.7 weeks compared with 41.4 weeks on Tykerb alone.

The survival benefit was maintained after adjusting for baseline prognostic factors, and a trend towards a clinically relevant 25% reduction in risk of death was seen on combination therapy after adjusting for crossover, reported the researchers led by Dr Kimberly Blackwell of Duke University Medical Center in North Carolina.

A final safety analysis found that the incidence of adverse events was similar in the monotherapy and combination arms, with the exception of grade 1 and grade 2 diarrhoea, which were significantly more prevalent in the Tykerb plus Herceptin group.

Commenting on the results, Dr Blackwell suggested the two drugs in combination “may be acting together to form a sort of ‘dual blockade’ to obstruct the HER2 pathway necessary for the tumour to thrive”.

This may involve “lapatinib working inside the cell and trastuzumab working outside the cell”, Dr Blackwell said, adding: “To achieve a survival advantage of greater than one year for this aggressive form of breast cancer is very encouraging”.

Tykerb is currently indicated in combination with Xeloda (capecitabine, Roche) for the treatment of patients with advanced or metastatic breast cancer whose tumours over-express HER2 and who have received prior therapy including an anthracycline, a taxine and Herceptin. GSK hopes to position Tykerb as first-line therapy in combination with hormone treatment, while trials are underway comparing Tykerb and Herceptin either head-to-head or as a combination versus monotherapy in early-stage breast cancer.

The annual CTRC-AACR symposium is organised by the Cancer Therapy & Research Center (CTRC) at UT Health Science Center, San Antonio and the American Association for Cancer Research (AACR).