Abstract P2-01-05: A phase II clinical trial of VST-1001 (dilute fluorescein) in lymphatic mapping and sentinel lymph node localization in clinically node negative breast cancer
Authors: Ross MI , Black DM , Mittendorf EA , Porretta JM , Bedrosian I , Caudle AS , Hwang RF , Meric-Bernstam F , Babiera GV , Brulotte M , Andtbacka RHI , Matsen CB 
Published: March 2017

Abstract
Background: Combined use of a radiocolloid and a vital blue dye is recommended for accurate lymphatic mapping and sentinel lymph node (SLN) identification in breast cancer. However, vital blue dyes can cause tattooing, skin necrosis and severe allergic reactions. Moreover, the vital blue dyes are only able to detect 70% or less of SLNs in large multi-center trials. Hence, there is an unmet need to develop new lymphatic mapping agents that could potentially replace vital blue dyes. We have previously, in a Phase I trial, reported on the safety of VST-1001 (dilute fluorescein) in SLN identification. Here we report the Phase II data of VST-1001 and direct visualization devices in lymphatic mapping, SLN identification, and safety in clinically node negative breast cancer.
Methods: This prospective Phase II, multi-center, non-randomized, single-arm, open-label, single-dose clinical trial enrolled patients (pts) with DCIS and clinical stage I/II breast cancer eligible for SLN biopsy. All pts had SLN localization with technetium-99m-sulfur colloid (Tc99mSC) and intraoperative lymphatic mapping with 0.1% VST-1001 injected peritumorally, periareolarly, and/or intradermally. SLN radioactivity was identified with a gamma probe, and VST-1001 fluorescence was induced by light emitting diodes and detected as yellowish-green fluorescence in the visible light range with notch filter spectacles. The primary endpoint was the ability of VST-1001 to localize lymph nodes. SLN concordance of Tc99mSC radioactivity and VST-1001 fluorescence, and safety were also assessed.
Results: Eighty-seven women and 2 men with a median age of 60 yrs (range, 37-77) were enrolled. Primary tumor T-stage was: 12.4% T0, 62.9% T1, 23.6% T2, and 1.1% T3. Of the 89 pts, 87 (97.8%) had at least 1 radioactive SLN, and 86 (96.6%) at least 1 fluorescent SLN. Of a total of 198 SLN identified (mean 2.2 SLN/pt), 74.2% were fluorescent and radioactive, 11.6% were radioactive only, 8.6% were fluorescent only, and 5.1% were not radioactive or fluorescent. 82.8% of all SLNs were fluorescent. Twelve (13.5%) pts had microscopic metastatic breast cancer in 14 (7.1%) SLNs. Of the 14 SLNs with metastasis, 12 (85.7%) were both radioactive and fluorescent, 1 (7.1%) fluorescent only and 1 (7.1%) not radioactive or fluorescent and only suspicious on palpation. The fluorescent only SLN was identified in a patient with only 1 SLN and without VST-1001 the metastasis would have been missed. The only adverse event related to VST-1001 was intraoperative grade 2 allergic reaction of the ipsilateral breast in one pt. Intravenous anti-histamines were administered and the erythema resolved.
Conclusions: VST-1001 safely localized lymph nodes in breast cancer. VST-1001 was able to localize lymph nodes that were not radioactive and had a high co-localization concordance with Tc99mSC. VST-1001 also appears to have a higher rate of SLN localization compared to that historically reported for vital blue dyes. In light of these data, VST-1001 may be an alternative SLN localizing agent to be used in conjunction with Tc99mSC in breast cancer pts, eliminating many of adverse events observed when using vital blue dyes without compromising SLN identification.
Citation Format: Ross MI, Black DM, Mittendorf EA, Porretta JM, Bedrosian I, Caudle AS, Hwang RF, Meric-Bernstam F, Babiera GV, Brulotte M, Andtbacka RHI, Matsen CB. A phase II clinical trial of VST-1001 (dilute fluorescein) in lymphatic mapping and sentinel lymph node localization in clinically node negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-05.