Lapatinib for aggressive inflammatory breast cancer

29 Apr 2009

Lapatinib could be used to treat inflammatory breast cancer, an aggressive from of the disease which represents up to one tenth of malignant breast cancer cases. The findings of this phase II study are discussed in an Article published Online First and in the June edition of The Lancet Oncology, written by Dr Stephen Johnston, Royal Marsden Hospital, London, UK, and Dr Bella Kaufman, The Chaim Sheba Medical Center, Tel Hashomer, Israel, and colleagues.

Inflammatory breast cancer makes up 1-6% of all invasive breast tumours in the USA and western Europe, and 5-10% in North Africa and Arabian countries. In this form of cancer, the protein human epidermal growth factor receptor 2 (HER2) — which is involved in the signaling pathways leading to cell growth — is expressed much more than in other, less aggressive breast cancers. Clinical symptoms are rapid onset of swelling, redness of the breast skin, fluid under the skin of more than two thirds of the breast which can result in a pitted appearance, tenderness, hardening, and warming of the breast.

For patients with resistance to conventional anthracycline or taxane and trastuzumab treatment, options are limited. Lapatinib is an oral inhibitor of HER2 and thus interferes with the mechanism of tumour growth. This study assessed 126 patients, all with inflammatory breast cancer, who were treated with lapatinib 1500 mg once daily. Skin disease was assessed every four weeks, and cancer progression, both local and secondary, was assessed using standard criteria.

The researchers found that although no patient showed complete response to the treatment, 49 of them (39%) had a partial response (a 50% decrease in extent of skin disease from baseline). Median progression-free survival was 15 weeks, with median duration of response 21 weeks. At 6 months, 22% of patients were still progression-free. Likelihood of response to lapatinib was not affected by previous treatment with trastuzumab. Median overall survival was recorded for four sets of patients: responded to lapatinib, previous trastuzumab (33 patients) — 18.4 months; responded to lapatinib, no previous trastuzumab (15) — 14.0 months; unresponsive to lapatinib, previous trastuzumab (61) — 8.4 months; and finally unresponsive to lapatinib, no previous trastuzumab (16) — 8.2 months. Adverse events were common, with 92% of patients suffering at least one. 32% of patients had serious adverse events most of which were not considered to be related to lapatinib — the most common of these were shortness of breath (eight patients) and fluid around the lungs (six). Five patients died from adverse events that were possibly treatment related.

The authors say: “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 conclude: “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.”