Lapatinib and Trastuzumab Combo Significantly Reduced HER2 Breast Cancer Tumors

The combination therapy of lapatinib and trastuzumab significantly reduced tumors 11 days after the diagnosis of HER2 positive breast cancer in a recent study.

Researchers from the Institute of Cancer Research conducted a multi-center, clinical trial called UK EPHOS-B, which enrolled 257 women recently diagnosed with operable cancer recruited between November 2010 and September 2015.

The study was broken into 2 parts: the first used 130 women randomized to receive only trastuzumab (Herceptin), only lapatinib (Tyverb), or a control group who received no pre-operative treatment for 11 days after diagnosis and prior to surgery.

The second part used 127 women randomized to be part of the control group, or to receive only trastuzumab, or the combinational therapy. This was adjusted after new evidence from other trials showed the efficacy of using the Tyverb and Herceptin combination to treat HER2 positive breast cancer.

Women in both trials were able to receive standard treatment after surgery.

Samples of tumor tissue taken from the first biopsy were analyzed to determine if there was any drop in levels of the Ki67 protein, which would be an indicator of cell proliferation or a rise in apoptosis.

Researchers also examined pathology reports of the tissue taken during surgery. The women were then put into 3 categories: if there was a pathological complete response (pCR) if no active cancer cells were found, minimal residual disease (MRD) if the tumor was less than 5mm in diameter, or other.

The results of the study showed that in addition to the drop in Ki67 levels, 11% of patients who received the combination treatment had pCR, while 17% had MRD.

Among women who received only Herceptin, 0% had pCR and 3% had MRD. There were no patients in the control group who had pCR or MRD.

“These results show that we can get an early indication of pathological response within 11 days, in the absence of chemotherapy, in these patients on combination treatment,” said lead trial researcher Judith Bliss. “Most previous trials have only looked at the pathological response after several months of treatment. Clearly these results need further confirmation, but I suspect the excitement from seeing the speed of disappearance of the tumors will mean that several trials will attempt to confirm these results.”

Currently, this is the only trial that examined the effects of using the combination therapy without chemotherapy in the 2 weeks between diagnosis and surgery.

“Other trials have looked at anti-HER2 therapy, with and without chemotherapy, including an assessment of the combination of trastuzumab and lapatinib, and have reported impressive response rates but these trials have only reported results after several months of therapy,” said study presenter Nigel Bundred. “Potentially, giving treatment while waiting for surgery can identify a group of patients whose disease is particularly sensitive to anti-HER2 therapy, which would allow individualization of therapy in women with HER2 positive cancers.”