A plenary study presented at the American Society of Clinical Oncology's annual meeting found that adding lapatinib (marketed as Tykerb) to trastuzumab (marketed as Herceptin) did not improve survival outcomes for women with early-stage breast cancer that is sensitive to HER2-targeted therapy.
This finding came as a shock and a disappointment for many breast cancer clinicians, researchers, patients and advocates, since lapatinib also acts upon the HER2 receptor, and an earlier trial on the lapatinib-trastuzumab combination showed promising results.
Despite this discouraging news, the study's lead author, Edith A. Perez, M.D., did find a silver lining when reporting her results.
"We were encouraged to see that most patients with HER2-positive early breast cancer are doing well with standard trastuzumab therapy," said Perez, a deputy director at large at the Mayo Clinic Cancer Center in Jacksonville, Florida, in a press release. "But we were surprised that adding lapatinib did not provide further benefit."
In this phase III clinical trial, called ALTTO, Perez and her colleagues followed more than 8,000 women with early-stage, HER2-positive breast cancer. After these patients underwent surgery, they were randomized to receive standard chemotherapy in combination with either trastuzumab, lapatinib, trastuzumab followed by lapatinib or trastuzumab concurrent with lapatinib.
After following up with these patients, the researchers found that the trastuzumab-only, trastuzumab then lapatinib and trastuzumab plus lapatinib groups had little — and statistically insignificant — differences in four-year survival rates at 86, 87, 88 percent, respectively (at the time of this report, data from lapatinib-only group were excluded.)
Providing outside commentary, James Waisman, M.D., clinical professor in City of Hope's Department of Medical Oncology & Therapeutics Research, said that, on a positive note, this trial's results spared women from an unnecessary treatment.
"The good news is that patients do not have to take an extra drug and suffer from the additional side effects associated with lapatinib, such as nausea, fatigue, diarrhea and skin rashes," Waisman said.
However, Waisman did express concern over what these results mean for other clinical research findings. A previous study, called neoALTTO, found that the adding lapatinib to trastuzumab improved the likelihood of a complete pathological response (i.e., eradication of the entire tumor when the drug is administered prior to surgery.)
"In this and other areas of breast cancer research, we had believed that a pathologic response can be a surrogate for a survival advantage; unfortunately, the results of ALTTO showed that to not be true," Waisman said.
The study's researchers and ASCO concur with Waisman's sentiments, noting in the press release that "the ALTTO study will influence the design of future breast cancer clinical trials" since complete pathological response may not necessarily mean better survival outcomes.
In the meantime, Perez and her team are evaluating data from the lapatinib-only group to present on a future date.
This study's abstract (LBA4) is available online on ASCO's website.
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