Many uses for Lapatinib

At the recent American Society of Clinical Oncology annual conference, positive clinical trial results with lapatinib in various cancer types were presented. Lapatinib is a dual kinase inhibitor that targets the epidermal-growth-factor receptors 1 (EGFR or ERBB1) and 2 (HER2 or ERBB2).

A phase III open-label study reported by Charles Geyer was designed to evaluate time to progression (TTP) in women with ERBB2-positive trastuzumab-resistant advanced breast cancer treated with lapatinib plus capecitabine, or capecitabine alone. Of 321 women evaluated, the median TTP in the combination group was 36.9 weeks, compared with 19.7 weeks in the monotherapy group. Median progression-free survival was 36.9 weeks on combination therapy versus 17.9 weeks on capecitabine alone. Survival data are not yet mature, but are similar so far. The superior efficacy of the combination therapy has led the Independent Data Monitoring Committee to recommend discontinuing enrolment into the trial.

In addition, Neil Spector reported the results of an ongoing phase II study of lapatinib monotherapy for women with relapsed or refractory inflammatory breast cancer. 62% of ERBB2 overexpressors had a complete or partial response; there were no responders in the group who overexpressed ERBB1 but not ERBB2. These data are based on only 57 patients, but they indicate that ERBB1 expression alone cannot predict sensitivity to lapatinib.

Another phase III trial was conducted in patients with advanced renal-cell carcinoma (RCC) — a tumour known to produce high levels of ERBB1. In this study, 417 patients with immunotherapy-refractory RCC were randomized to receive standard second-line hormonal therapy or lapatinib. Alain Ravaud reported that while overall survival and TTP were similar, those 241 patients who greatly overexpressed ERBB1 had longer TTP if on lapatinib rather than hormonal therapy (15.1 weeks versus 10.9 weeks), as well as overall survival (46 weeks versus 37.9 weeks). Follow-up in this trial is continuing. WEB SITEhttp://www.asco.org

Focusing on African-American women

African-American women with breast cancer are known to have a poorer prognosis than non-African-American women. A case–control study reported in JAMA is unique in that it oversampled African-American and pre-menopausal women to enable better evaluation of these populations in terms of tumour subtype and survival than has previously been possible.

496 incident cases of invasive breast cancer were included and subtyped into luminal, basal-like, ERBB2 positive and oestrogen-receptor negative (ER−), and unclassified. Basal-like breast cancer was the most prevalent subtype among pre-menopausal African-American women (39%) compared with postmenopausal African-American women (14%) or non-African-American women of any age (16%). Conversely, the luminal subtype was less prevalent. There was no difference within the ERBB2+ER− subtype with regards to race or menopausal status. The overall disease-specific survival was 80%, but the shortest survival was among the ERBB2+ER− (52%) and basal-like subtypes (75%). These findings could contribute to the poor prognosis of young African-American women with breast cancer, but additional studies of long-term survival in other African-American populations are required to confirm this. ORIGINAL RESEARCH PAPER Carey, L. A. et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295 2492–2502 (2006)