Pilot trial of paclitaxel-herceptin adjuvant therapy for early stage breast cancer (E2198)

The combination of doxorubicin and trastuzumab is associated with an increased risk of congestive cardiomyopathy, and paclitaxel plus trastuzumab following anthracyciine-based chemotherapy has been associated with a low but real incidence of cardiac events in the pivotal Herceptin metastatic trial. Cardiomyopathy therefore represents a possible barrier to the use of trastuzumab in the adjuvant setting. Methods: E2198 examined the cardiac effects of paclitaxel plus trastuzumab (TH) prior to doxorubicin plus cyclophosphamide (AC) in 234 HER-2-positive (IHC 2+ or 3+) stage II breast cancer patients. Patients (pts) were randomized either to T 175 mg/m² q3w × 4 + H (4 mg/m² loading dose followed by 2 mg/m2 × 9w) followed by AC × 4. or to the same regimen followed by 52 weeks H. Cardiac monitoring for LVEF (by MUGA or echocardiogram) was performed at baseline, post-TH, and at multiple points following AC. Results: Drops in LVEF > 10% (absolute) from baseline levels were seen in 18 of 189 of pts (9.5%) post-TH, and in 16 of 128 pts (12.5%) post-AC. Drops in LVEF below the lower limit of normal were seen in 4 of 189 pts post-TH, and in 7 of 128 pts post-AC. Grade 3/4 LVEF events (CTC grading) were seen in 8 patients (7 grade 3, 1 grade 4) in the entire study, with one case of CHF reported post-TH. No excess non-cardiac toxicity was seen in this adjuvant population. Conclusion: We conclude that TH has rare but real cardiac effects in anthracycline- naive patients receiving adjuvant chemotherapy. Updated post-AC data will be presented, as will data comparing IHC and FISH determinations.