From the American Society of Clinical OncologyTrial Stopped Early
ATLANTA?Physicians treating women with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer, an especially aggressive form of the disease, may soon have a much-needed therapeutic alternative, as indicated by data announced at the American Society of Clinical Oncology annual meeting.
Interim results from a pivotal phase 3 trial show that the experimental drug lapatinib ditosylate (Tykerb; GlaxoSmithKline) delayed tumor growth almost twice as long as standard chemotherapy in patients who no longer responded to trastuzumab (Herceptin) and/or other agents.
"Tykerb, a second-generation targeted therapy, was designed for the 20% to 25% of refractory metastatic breast cancer patients whose fast-growing tumors start proliferating again after being controlled for a time with Herceptin plus chemotherapy," explained lead investigator Charles Geyer, Jr, MD, director of breast medical oncology at Alleghany General Hospital, Pittsburgh, Pa.
Trastuzumab, which blocks the signals that stimulate cancer growth, is the current gold standard treatment for late-stage breast cancer patients with HER2+ disease. Worldwide, >230,000 women have been treated with this agent since 1998.
Interim findings from 321 patients (of a total of 392 enrollees) showed that lapatinib plus the older, more established chemotherapeutic agent capecitabine (Xeloda) nearly doubled the time to progression compared with capecitabine alone (8.5 vs 4.5 months, respectively), Dr Geyer said.
In fact, lapanitib's effects were so impressive that the trial was stopped early, and the investigational oral therapy was offered to all participants.
But approximately 14%?of the patients taking the lapanitib/capecitabine combination dropped out of the trial because of adverse effects, compared with 11% taking capecitabine alone. Lapatinib-related complications included diarrhea and rash, including a particularly severe form of rash called hand?foot syndrome.
A related team studied lapatinib as a possible treatment for brain metastases?a complication in one third of patients with HER2+ metastatic breast cancer. Preliminary analysis showed that tumors recurred in 4 women receiving lapatinib plus chemotherapy compared with 11 women receiving chemotherapy alone.
"While these findings are encouraging, many more studies must be done to confirm them," said Paolo Paoletti, MD, a spokesperson for the manufacturer. "Treatment for brain metastases is an area of significant unmet need. Once the diseaseadvances to this stage, prognosis is poor, with the average 1-year survival at about 20%."
This investigational agent is currently being studied as monotherapy in a large, international, randomized trial involving patients with brain metastases that is using magnetic resonance imaging to monitor the lesions in the brain.
GlaxoSmithKline plans to apply for FDA approval of lapatinib later this year; meanwhile, it is working with the FDA to distribute the drug free of charge to needy women with advanced breast cancer.