Annals of Surgical Oncology
Background/Objective: Positive margins detected after breast conservation surgery can result in the need for a re-excision or completion mastectomy. We hypothesized that pegloprastide combined with a ratiometric fluorescence imaging system would allow surgeons to detect positive margins in real time. Methods: Pegloprastide (AVB-620) was to be administered to patients 3-20 hours before the start of surgery. During the operation, initial primary tumor removal was performed unaided. Following primary resection, a fluorescence imaging system optimized for use with pegloprastide was used to assess the primary specimen and the cavity. Cavity shaves were taken when fluorescence above pre-specified thresholds were noted. Additional cavity shaves for areas negative by imaging were also sampled. Comparisons were made between images and final pathology results to assess the correlation between pegloprastide-mediated imaging and margin status. Pathologic margins were deemed to be positive if invasive cancer showed tumor on ink (0mm) or DCIS was within 2mm of the surface or a positive shave margin was identified. Preplanned subgroup analysis was performed based on dose timing, comparing Day before Surgery (DBS) versus Same Day as Surgery (SDS). Results: Ninety-two patients received pegloprastide. There were no drug-related serious adverse events recorded. The average age was 59.5 (40-81), 85% of patients were ER-positive, and 9% of patients were HER2-positive. Ninety-six percent of patients underwent a lumpectomy. Of the 92 patients, 87 were evaluable and were divided into 2 groups based on the timing of the pegloprastide dose, either DBS (n=47) or SDS (n=40). Overall, the positive margin rate as measured at the end of the primary resection was 46% (40/87). The overall patient level positive margin sensitivity and specificity were 45% and 70% respectively. When measured by dosing subgroup, there was a significant difference (p=0.005) in sensitivity with DBS showing a 65% true positive rate (13/20), compared to 25% (5/20) for SDS group. Beyond that, in the DBS patient group, an additional 10% of patients (2/20) with positive margins, who did not have the positive margin area detected by fluorescence (a false negative), had a close margin (defined as invasive tumor within 2mm of the surface) fluorescently detected, such that 75% (15/20) of margin positive patients actually had a positive fluorescent signal seen. Specificity was 78% in the DBS group and 60% in the SDS group. Sample level accuracy was 82% for DBS and 79% for SDS. Re-excision rates in the trial were 6%. Conclusions: Pegloprastide is well tolerated. When infused the day before surgery, pegloprastide demonstrates the ability to identify positive margins in at least 65% of patients. Utilization of pegloprastide, particularly when dosed the day before surgery, may aid in allowing surgeons to identify and resolve positive margins in real time in a substantial proportion of patients.
McLaughlin SA, Lee MC, Feldman SM, Rosen B, Grignol VP, Wallace AM, et al. [Dekhne NS] Pegloprastide-based ratiometric fluorescence imaging detects intraoperative positive margins in real-time. Ann Surg Oncol 2021 May;28(S2):S230–231.