An article published online First and in the June edition of The lancet Oncology reports the findings of a phase II study on inflammatory breast cancer, an aggressive form of the disease representing up to one tenth of malignant breast cancer cases. Dr Stephen Johnston, Royal Marsden Hospital, London, UK, and Dr Bella Kaufman, The Chaim Sheba Medical Center, Tel Hashomer, Israel, and colleagues discuss how lapatinib may be beneficial in the treatment of this form of cancer.
In inflammatory breast cancer, the protein epidermal growth factor receptor 2 (HER2) implicated in the signaling pathways leading to cell growth is manifested much more than in other less aggressive cancers. This disease makes up one to six percent of all invasive breast tumors in Western Europe and the USA and five to ten percent in North Africa and Arabian countries. The clinical symptoms are: rapid onset of swelling, redness of the breast skin, fluid under the skin of more than two thirds of the breast resulting in a bumpy appearance, painfulness, hardening and warming of the breast.
Lapatinib hinders tumor growth because it is an oral inhibitor of HER2. Options are limited for patients with resistance to conventional anthracycline or taxane and trastuzumab treatment. The study included 126 patients receiving a daily dose of lapatinib (1,500 mg). Every four weeks, skin disease was evaluated and cancer evolution (local and secondary) was assessed using standard criteria.
Findings showed that none of the patients had an absolute response to the treatment but 39 percent (49 patients) had a partial response with a 50 percent healing in extent of skin disease from baseline. The average progression-free survival was of fifteen weeks, with an average duration of response of twenty one weeks. Six months later, 22 percent of patients were still progression-free. The probability of response to lapatinib was not altered by prior treatment with trastuzumab. The general average of survival was accounted for four groups of patients:
• 33 patients who responded to lapatinib and had previous treatment with trastuzumab. Median survival: 18.4 months.
• 15 patients who responded to lapatinib and had no previous treatment with trastuzumab. Median survival: 14.0 months.
• 61 patients unresponsive to lapatinib and previous treatment with trastuzumab. Median survival: 8.4 months.
• 16 patients unresponsive to lapatinib with no previous trastuzumab treatment. Median survival: 8.2 months.
Undesirable events were frequent since 92 percent of patients experienced at least one. Although the majority was not considered linked to lapatinib, 32 percent of patients suffered serious adverse events: eight of them experienced shortness of breath, and six of them had fluid around the lungs. There were five deaths from adverse events that were possibly treatment related.
The researchers point out: “Patients who responded to treatment with lapatinib had a longer median overall survival than did those patients who did not respond, irrespective of previous exposure to trastuzumab. Patients exposed to previous trastuzumab treatment who experienced a response to lapatinib had the longest median overall survival. This finding confirms the clinical benefit of targeted therapy in these patients.”
They write in conclusion: “Lapatinib monotherapy is potentially clinically effective in heavily pretreated patients with inflammatory breast cancer with HER2+ tumours. The objective response rate noted…coupled with the median duration of response and median overall survival supports a role for lapatinib in these patients.”
Written by Stephanie Brunner (B.A.)