551 Background: We have previously shown that neoadjuvant cisplatin has activity in TNBC, a subtype of breast cancer for which there is no effective targeted therapy. Bevacizumab adds to the efficacy of chemotherapy in metastatic breast cancer; however, there is limited data on the safety or efficacy of bevacizumab in combination with chemotherapy in the neoadjuvant or adjuvant setting. Thus, we sought to explore the safety and efficacy of the addition of bevacizumab to cisplatin in the treatment of TNBC.
METHODS
51 patients (pts) with confirmed TNBC provided informed consent and were enrolled in a single arm phase II trial of neoadjuvant cisplatin 75 mg/m2 q 3 weeks x 4 cycles and bevacizumab 15 mg/kg q 3 weeks x 3 cycles prior to definitive surgery. Only 3 cycles of bevacizumab were delivered to allow 6 weeks between the last dose of bevacizumab and surgery. Research biopsies were obtained and breast MRI performed before treatment and at surgery. Postoperatively, pts received doxorubicin and cytoxan (AC) plus bevacizumab or AC/Taxol plus bevacizumab. Median age was 50 yrs (range 30 to 66 yrs); tumors were clinical T1 (2%), T2 (80%), T3 (18%).
RESULTS
Forty-six pts are evaluable for response and 5 pts are still receiving neoadjuvant therapy. Clinical responses to date: 12/46 (26%) clinical complete response (cCR), 24/46 (52%) clinical partial response (cPR), 5/46 (11%) stable disease (SD), and 1/46 (2%) progressive disease (PD). Non-responders included 4/46 (9%) pts who discontinued protocol therapy for toxicity. To date, 7/46 (15%) pts achieved a complete pathological response (Miller-Payne 5) and an additional 10/46 (22%) were Miller-Payne 4. Five pts did not complete neoadjuvant therapy, 2 with tinnitus/hearing loss and 3 with grade 4 toxicities consisting of refractory hypertension in 1 pt and pulmonary embolism (PE) in 2 pts. Tissue-based assays to predict platinum/bevacizumab responses, including BRCA1/2 status, are underway.
CONCLUSIONS
Cisplatin and bevacizumab has some activity in TNBC as demonstrated by 37% of evaluable pts with a Miller-Payne 4 or 5 pathological response. However, toxicity, including tinnitus/hearing loss, hypertension and PE, limited completion of neoadjuvant therapy in 11% of pts. No significant financial relationships to disclose.