[1] A phase II combination study of lapatinib and paclitaxel as a neoadjuvant therapy in patients with newly diagnosed inflammatory breast cancer (IBC).

Cristofanilli M, Boussen H, Baselga J, Lluch A, Ben Ayed F, Friaha M, Ben Ahmed S, Hurley J, Johnston S, Kaufman B, Findlay M, Olopade O, Shannon C, Harris J, Stein S, Spector N.. MD Anderson Cancer Center, Houston, TX; Institute Salah Azalez, Tunis, Tunisia; Vall dHebron University Hospital, Barcelona, Spain; Chu Ferhat Hached, Suisse, Tunisia; University of Miami, Miami, FL; The Royal Marsden Hospital, London, United Kingdom; Chaim Sheba Medical Center, Tal Hashomer, Israel; University of Auckland, Grafton, New Zealand; University of Chicago, Chicago, IL; Maler Adult Hospital, Brisbane, Queensland, Australia; GlaxoSmithKline, Durham, NC

Background: IBC, which tends to overexpress ErbB2 and/or express ErbB1 is the most lethal form of breast cancer. Lapatinib (Tykerb), a small molecule dual inhibitor of ErbB1 and ErbB2 tyrosine kinases has demonstrated anti-tumor activity in preclinical models of ErbB2-overexpressing breast cancers and in a clinical trial of heavily pre-treated IBC patients refractory or relapsed following prior anthracycline therapy. Here we will discuss the clinical activity, safety, and pharmacodynamics of this Phase II study evaluating the combination of lapatinib and paclitaxel as a neoadjuvant therapy for primary IBC.
Material and Methods: Newly diagnosed primary IBC patients were enrolled on this phase II trial and assigned to one of two cohorts: Cohort A- ErbB2 overexpressing tumors; Cohort B- ErbB1+/ErbB2 non-overexpressing. Assignment to cohorts was based on biomarker analysis at an independent reference laboratory. Lapatinib (1500 mg) was administered orally once daily as a monotherapy (days 1-14) followed by an additional 12 weeks in combination with weekly paclitaxel 80 mg/m2. The primary objective was pathological complete remission (pCR) in breast and lymph nodes at the time of definitive surgical resection upon completing 14 weeks of therapy. Secondary objectives included clinical response, pharmacodynamics and safety.
Results: Forty-nine patients (42 Cohort A; 7 Cohort B) were registered. Fifteen patients (13 in Cohort A; 2 in Cohort B) were considered non-eligible. In Cohort A, 79% expressed activated, phospho-ErbB2. Adverse events were generally grade 1/2 GI and skin toxicity with 1 grade 3 cardiotoxicity necessitating withdrawal. Of the evaluable patients in Cohort A, 95% (20/21) had a clinical response with 12 patients responding in both RECIST measurable and chest wall sites of disease. In Cohort B, 100% (2/2) of evaluable patients responded in RECIST and chest wall sites. Pathological response data will be available.
Discussion: This preliminary analysis suggests that compared with historical chemotherapeutic regimens, the combination of daily lapatinib and weekly paclitaxel is generally well-tolerated with significant clinical activity as a neoadjuvant treatment regimen for ErbB2-overexpressing or ErbB1-expressing IBC warranting further investigation.

Thursday, December 14, 2006 9:45 AM

General Session 1 (9:45 AM-11:00 AM)