, new phase 3 findings show.
Pegulicianine (Lumisight), an investigational and activatable fluorescent imaging agent used with a novel direct visualization system, helped identify residual tumor or circumvent second surgeries in about 10% of patients in the trial.
Use of the agent and direct visualization system – both from Lumicell and currently under review by the Food and Drug Administration – could provide more complete resection for patients with early breast cancer and avert the need for reexcisions, the investigators write.
The findings were published online in NEJM Evidence and were subsequently presented at the annual meeting of the American Society of Breast Surgeons.
Local recurrence following lumpectomy increases the risk of dying from breast cancer, and the risk of local recurrence is directly linked to inadequate tumor removal during lumpectomy. In about 20%-40% of lumpectomies, positive margins are identified after surgery.
To improve patient outcomes, investigators assessed whether a novel fluorescence-guided surgery system helped surgeons perform more complete resections during lumpectomy.
In the Novel Surgical Imaging for Tumor Excision (INSITE) trial, 392 patients were randomly assigned to undergo pegulicianine fluorescence-guided surgery (n = 357) or standard lumpectomy (n = 35).
To prevent surgeons from performing a smaller than standard lumpectomy in anticipation of using the pegulicianine fluorescence-guided system, patients were randomly assigned to the pegulicianine fluorescence-guided surgery group or the control group. The groups were revealed only after the surgeon completed the standard lumpectomy.
“Randomization was not designed to provide a control group for analysis of device performance,” The authors explain. “In this study design, each patient undergoing pegulicianine fluorescence-guided surgery served as her own control,” they write. The investigators compared final margin pathology after standard lumpectomy and after guided surgery. Those in the control group were included in the safety analysis.
Study participants were women aged 18 years or older who were undergoing lumpectomy for stage I–III breast cancer and/or ductal carcinoma in situ. All patients received pegulicianine 1.0 mg/kg via a 3-minute intravenous infusion 2-6 hours before surgery.
The agent produces a signal at sites of residual tumor, and a handheld probe illuminates the cavity during surgery. A tumor detection algorithm then analyzes and displays the images to the surgeon in real time – an overall process that adds about 7 minutes to the operative procedure, the authors say.
Investigators identified invasive cancers in 316 patients and in situ cancers in 76 patients. Among the 357 patients in the treatment group, 27 (7.6%) were found to have residual tumor after standard lumpectomy. For 22 patients, cavity orientations were deemed negative on standard margin evaluations, the authors report.
With use of pegulicianine fluorescence-guided surgery, positive margins were converted to negative margins for 9 of 62 patients (14.5%), potentially averting a second surgery in those patients.
Overall, the authors say that pegulicianine fluorescence-guided surgery removed residual tumor (27 of 357) or avoided second surgeries (9 of 357) in 10% of patients in the trial.
The current trial findings confirm results regarding the safety and efficacy of pegulicianine fluorescence-guided surgery and the direct visualization system that were reported in a prior multicenter feasibility study, the authors say.
Pegulicianine fluorescence-guided surgery met prespecified thresholds for removal of residual tumor and specificity, at 85.2%, but did not meet the prespecified threshold for sensitivity, which was only 49.3%.
The rate of serious adverse events with pegulicianine was 0.5% (two patients), similar to that of other contrast agents. Administration of the agent was stopped because of adverse events for six patients, the investigators write.
Serious adverse events included grade 3 hypersensitivity in one patient and an anaphylactic reaction in another. The other four adverse events included an allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation. All adverse events resolved, and patients proceeded to standard lumpectomy.
Overall, the trial findings “suggest that a more complete breast cancer resection may be achieved” with pegulicianine fluorescence-guided surgery and the direct visualization system, lead investigator Barbara Smith, MD, PhD, director of the breast program at Massachusetts General Hospital and professor of surgery at Harvard Medical School, both in Boston, said in a press release. “Given the low complication rate, minimal added operative time and, most importantly, the discovery of additional cancer left behind after a lumpectomy, the Lumicell [system] has the potential to be a critical adjunct to enhance standard practice for breast cancer patients.”
The system also has the potential to reduce “the patient burden of additional surgery” and decrease “costs associated with a return to the operating room,” the authors conclude.
The INSITE trial was funded by Lumicell and the National Institutes of Health. Dr. Smith reported unpaid research collaboration with Lumicell.
A version of this article first appeared on Medscape.com.