Abstract
Abstract Background:Trastuzumab has significantly improved pathological complete response rates of neoadjuvant treatment in HER2 positive breast cancer (HER2+BC). The tyrosine-kinase inhibitor lapatinib (L) has shown efficacy in metastatic breast cancer. Previous data in metastatic breast cancer suggested increased hematologic toxicity of docetaxel (Doc) combined with L. As the dose and safety of L in combination with epirubicin (E), cyclophosphamide (C), and Doc has not yet been adequately tested, an integrated safety phase was conducted.Patients and Methods:The GeparQuinto trial, a neoadjuvant phase III study, planned to include 2500 patients (pts) in total and 594 HER2+BC pts for comparing L versus trastuzumab (H) given concomitantly to anthracycline-taxane based chemotherapy. Female pts with untreated, histologically confirmed uni- or bilateral, cT3/4a-d, HER2+BC and no clinically relevant cardiovascular co-morbidities received 4 cycles of E (90mg/m²) + C (600 mg/m²) q3w followed by Doc 100mg/ m² q3w. Pts were randomized to receive either H (6 mg/kg; 8mg/kg loading dose; q3w) or L given concomitantly to all cycles. The 1st cohort in the L arm received 1000 mg/d L during the 1st cycle EC and the 1st cycle Doc and 1250 mg/d L through all other cycles and received prophylactic treatment with pegfilgrastim (6 mg on day 2) and loperamide (2x2mg daily). The 2nd cohort received no loperamide, if <=1 diarrhea grade 3 and no pegfilgrastim if <=3 events of grade 4 neutropenia and <=1 febrile neutropenia (FN) occurred during cycles 1+2 of the 1st 10 pts of the 1st cohort. The remaining pts received 1250 mg/d L in the first cycle and no prophylaxis with loperamide if <=2 diarrhea grade 3 and <= 1 diarrhea grade 4 and no pegfilgrastim if <=4 events of grade 4 neutropenia and <=2 FN occurred during cycles 1+2 of the 1st 10 pts of the 2nd cohort. An interim safety analysis was planned when 60 pts completed all cycles.Results:As of June 1 2009 918 (178 HER+BC) pts have been recruited. 31 pts received ECH-DocH and 29 pts ECL-DocL. In the 1st cohort no grade 3 diarrhea and 2 grade 4 neutropenias occurred. In the 2nd cohort again, no grade diarrhea 3, but 8 grade 4 neutropenias (1 FN) occurred in 4 pts. L was, when compared to H, associated with less grade 1/2 anemia (27.6% vs. 51.6.%) but more grade 1/2 skin rash (27.6% vs. 6.5%) during cycle 1 (data on all cycles will be presented). No significant differences for other toxicities were seen.Conclusion:L at a dose of 1250 mg/d is feasible and well tolerated when given concomitantly to EC-Doc if G-CSF is given prophylactically during DocL. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1094.
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