Gajria D et al. Proc SABCS 2010;Abstract P

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Presentation transcript:

Gajria D et al. Proc SABCS 2010;Abstract P6-11-12. A Novel Capecitabine Schedule (7 on – 7 off) is Feasible with Lapatinib for Patients with HER2-Positive Metastatic Breast Cancer Refractory to Trastuzumab Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Objectives Hypothesis Lapatinib in combination with an optimal schedule of capecitabine 7 days on, 7 days off (7-7) will be feasible and active in patients with HER2-positive metastatic breast cancer refractory to trastuzumab. Primary endpoint To evaluate complete and partial response rates according to RECIST criteria. Secondary endpoints Toxicity Stable disease for more than 6 months Progression-free survival at 6 months Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Study Design Eligibility Metastatic breast cancer (mBC) Accrual: 23 (Closed)* All Eligible Patients Eligibility Metastatic breast cancer (mBC) HER2-positive (IHC3+ or FISH>2) Disease progression following trastuzumab No more than 2 prior chemotherapy regimens No prior use of fluoropyrimidine for metastatic disease LVEF ≥50% by MUGA scan Lapatinib 1,250 mg daily X 2,000 mg BID 7 d off X 2,000 mg BID 7 d off 1 2 3 4 Week X = Capecitabine * Study closed to further accrual due to slower than expected accrual and an anticipated randomized Phase III trial comparing capecitabine (7–7) to standard capecitabine dose (14 days on, 7 days off) Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Patient Characteristics Median age, years (range) 54 (34-72) Median ECOG PS (range) 0 (0-2) ER- or PR-positive, n 13 HER2-positive, n 23 Sites of metastases, n Visceral metastases Brain metastases 16 3 Median number of prior regimens for mBC (range) 1 (0-2) Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Best Response Complete response Confirmed partial response 4 (17%) Outcome Patients n = 23 Complete response Confirmed partial response 4 (17%) Stable disease, >6 months 6 (26%) Stable disease, <6 months 12 (52%) Progressive disease 1 (4%) Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Treatment Modifications Outcome Patients n = 23 Discontinued treatment due to toxicity* 4 Capecitabine dose reductions or delays 10 Lapatinib dose reductions or delays 3 LVEF declines requiring treatment modification *Grade 2 LFTs, Grade 2 hand-foot-mouth syndrome and Grade 2 rash associated with lapatinib Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Adverse Events Anemia 2 (9%) 1 (4%) Hand-foot syndrome 9 (39%) Toxicity Grade 2 n (%) Grade 3 Grade 4 Anemia 2 (9%) 1 (4%) Hand-foot syndrome 9 (39%) Thrombocytopenia Neutropenia Diarrhea 6 (26%) Liver dysfunction 4 (17%) Fatigue Nausea Vomiting Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Author Conclusions Capecitabine 7-7 plus lapatinib demonstrates activity and feasibility in patients with HER2-positive, trastuzumab-refractory, metastatic breast cancer. – Confirmed partial response rate = 17% – Stable disease >6 months = 26% The combination of capecitabine 7-7 and lapatinib was associated with mild gastrointestinal toxicity. – No reports of ≥Grade 3 nausea, vomiting or diarrhea These data have informed the design of a Phase III study that will evaluate capecitabine 7-7 versus standard capecitabine dosing (14 days on/7 days off). Gajria D et al. Proc SABCS 2010;Abstract P6-11-12.

Investigator Commentary: Capecitabine (7 on, 7 off) with Lapatinib in HER2-Positive mBC Refractory to Trastuzumab This study from Memorial Sloan-Kettering was based on mathematical modeling, which suggested that capecitabine administered on a seven days on, seven days off schedule may be more efficacious and tolerable than the standard 14 days on, seven days off schedule. The investigators evaluated an all-oral regimen with the 7/7 schedule of capecitabine in combination with lapatinib in patients with HER2-positive metastatic breast cancer that was refractory to trastuzumab. They demonstrated that the combination was feasible, with response rates of approximately 20 percent. Their experience is not large enough to make any definitive conclusions, although much larger studies have evaluated this combination but not with this schedule of capecitabine. The side effects observed in this study were mild, with some hand-foot syndrome but no significant diarrhea or nausea/vomiting. It’s a small study, but it suggests that lapatinib can be combined with this novel schedule of capecitabine. Interview with William J Gradishar, MD, January 4, 2011