CHICAGO, IL—Adding bevacizumab to neoadjuvant trastuzumab plus docetaxel in tumors with a low likelihood of pathologic complete response (pCR) increased the pCR rate from 24.0% to 43.8%, a phase 2 study concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
The low likelihood of pCR was predicted based on relative change in fluorodeoxyglucose (FDG) tumoral uptake (ΔSUV) after one cycle of trastuzumab plus docetaxel by positron emission tomography (PET).
These results from the open-label multicenter AVATAXHER trial suggest that “PET ΔSUV, by selecting low-responding HER2-positive tumors, may be a useful tool for optimizing neoadjuvant therapy for HER2-positive breast cancer,” said Bruno P. Coudert, MD, of the Department of Medical Oncology, Centre Georges-Francois Leclerc, Dijon, France, and colleagues.
Adults with stage T2/3, N0/1 HER2-positive breast cancer received two 3-weekly cycles of trastuzumab 8 mg/kg, then 6 mg/kg with docetaxel 100 mg/m2.
“Those with 70% [or greater] ΔSUV in PET values between cycle 1 and 2 received four more cycles of trastuzumab plus docetaxel, one cycle of trastuzumab, then surgery (standard arm),” Dr. Coudert said.
Those with less than 70% ΔSUV were randomly assigned 2:1 to four cycles of trastuzumab plus docetaxel plus bevacizumab 15 mg/kg (Arm A) or trastuzumab plus docetaxel (Arm B), then one trastuzumab cycle and surgery. The primary endpoint was pCR rate at surgery. The positive (PPV) and negative predictive value (NPV) of ΔSUV on pCR rate and safety were also investigated.
Of the 152 patients recruited at 26 sites, 142 received treatment, with 53.6% (37 of 69 patients) in the standard arm achieving pCR, as did 43.8% (21 of 48 patients) in Arm A and 24.0% (6 of 25 patients) in Arm B. The pCR rates in patients with hormone receptor–negative versus –positive disease were 69.0%/42.5% in the standard arm, 57.9%/34.5% in Arm A, and 40.0%/13.3% in Arm B.
Among the 133 patients who received surgery, the procedure was conservative in 84.8% of patients in the standard arm, 67.4% in Arm A, and 62.5% in Arm B.
In patients who did not receive bevacizumab, ΔSUV after one cycle predicted pCR with a PPV of 52.9% and a NPV of 75%.
Toxicity was mild; all patients had at least one adverse event (AE). Grade 3/4 AEs were observed in 22.4% of patients in the standard arm, 40.4% in arm A, and 36.0% in Arm B. These included neutropenia (4.5%, 17.0%, and 12.0%, respectively); wound healing complications (2.1% of patients in Arm A); hypertension (4.0% of patients in Arm B); and arterial/venous thromboembolism (2.1% in Arm A). No grade 3/4 cardiac AEs were observed.
- Coudert BP, Pierga JY, Mouret-Reynier MA et al. Abstract 507. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.