Pafolacianine Detects Microlesions in Folate Receptor–Positive Ovarian Cancer

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Pafolacianine used during ovarian cancer surgery identified additional tumors that were not detected with conventional means and not otherwise planned for resection, according to results from a phase 3 study recently published in the Journal of Clinical Oncology.

Pafolacianine (Cytalux) used during ovarian cancer surgery identified additional tumors that were not identified with conventional means and not otherwise planned for resection compared with placebo, according to results from a phase 3 study (NCT03180307) published online in September 2022.1,2

Pafolacianine, an optical imaging agent targeting folate receptor (FR) which may be overexpressed in ovarian cancer, plus near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation in 33.0% of patients (95% CI, 24.3-42.7; P < .001). The result exceeded the prespecified threshold of 10%.

“You can imagine 33% of the patients would otherwise walk out from the hospital with a leftover tiny lesion left behind, which might decrease the survival benefit what the surgery can cause or make the prognosis worse,” lead author Janos L. Tanyi, MD, PhD, an associate professor of obstetrics and gynecology in the Perelman School of Medicine at the University of Pennsylvania, said in an interview with OncLive®.

The rate of detection was 39.7% (95% CI, 27.0-53.4; P <.001) with pafolacianine among patients who underwent interval debulking surgery. The sensitivity to detect ovarian cancer was 83% with a patient false-positive rate of 32.6%. Investigators reported achieving complete R0 resection in 62.4% of patients.

Tanyi described the modality as real-time intraoperative fluorescence imaging that uses a tumor-specific marker, pafolacianine. The fluorescent drug binds with a 1nM affinity to FR-expressing cancer cells, internalizes through receptor-mediated endocytosis, and accumulates in FR-positive cancer tissues. Following conventional intravenous administration, the drug will glow under near-infrared light.

“This helps us to identify these lesions because using this interpretive molecular imaging system, those lesions are glowing, and easy to find and identify,” Tanyi said. “[That] helps the surgeon to find them, accurately identify them, and remove them. The lesions are sometimes very small and difficult to identify, or they are retroperitoneal like tumor infiltrating lymph nodes, which are not palpable if they are in normal size, but with this methodology, they are glowing, so we are able to identify them.”

He noted that investigators asked the surgeons for their opinions about interpreting molecular imaging and 56% reported that they changed the prefluorescence surgical plan based on the imaging. Fifty percent persons found that did more complete debulking and 62% reported achieving R0 debulking with this methodology.


The goal of laparotomy for ovarian cancer remains complete R0 cytoreduction. Previously published data have established that a negative correlation between extent of residual disease following surgery and patient survival in ovarian cancer. This phase 3, multicenter study evaluated whether pafolacianine would identify cancer lesions not identified by the surgeon by white light or palpation and improve completeness of cytoreduction.

Tanyi noted that the rate of false positives was fairly high, and removal of false-positive lesions can increase surgical risk. However, investigators analyzed this patient population and determined that removing those false-positive lesions did not worsen the safety profile of the surgery and the imaging. Furthermore, the rate of false positives declined as surgeons gained more comfort using the technology.

“We evaluated the false positive rate of those particular surgeons who did more than 5 interpretive molecular imagings,” he added. “We found that the false positive rate decreased down to 28% with more experience using this technology and the sensitivity increased. [There are] definitely learning curves associated with these results.”
Investigators recruited patients with known or suspected ovarian cancer who were scheduled to receive cytoreductive surgery from March 2018 through April 2020. A total of 150 patients who received a single of dose of pafolacianine were included as the safety set and 109 patients with folate receptor–positive ovarian cancer could be evaluated for efficacy.

The FDA approved pafolacianine for use in adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions in November 2021.3 Pafolacianine is said to be the first targeted fluorescent imaging agent that illuminates ovarian cancer intraoperatively, providing the ability to detect more cancer for surgical removal. The imaging agent is administered as standard intravenous injection over a 1-hour period, before binding to folate receptors that are overexpressed in most epithelial ovarian cancers and illuminates intraoperatively under near-infrared light.

The approval was based on findings from a phase 3 study of 29 adult patients with a primary diagnosis or high clinical suspicion of ovarian cancer. Participants received pafolacianine sodium injection prior to planned debulking surgery.

Previous findings from the 006 study showed that pafolacianine identified additional lesions in 27% of patients (N = 134; 95% CI, 0.196-0.352).4 When controlling for correlation of detection among multiple lesions within a single patient, pafolacianine had a sensitivity of 97.97% (95% lower boundary CI = 87.75) and a positive predictive value of 94.93% (95% lower boundary CI = 86.13). Additionally, 48.3% (n = 14/29; 95% CI, 0.29–0.67) of patients had at least 1 additional lesion detected by pafolacianine sodium injection.5

Adverse events included nausea, vomiting, abdominal pain, flushing, indigestion, chest discomfort, and itching.


  1. Tanyi JL, Randall LM, Chambers SK, et al. A phase III Study of pafolacianine injection (OTL38) for intraoperative imaging of folate receptor–positive ovarian cancer (Study 006). J Clin Oncol. Published online September 7, 2022. doi: 10.1200/JCO.22.00291
  2. On Target Laboratories announces publication in Journal of Clinical Oncology of results from phase 3 trial of CYTALUX® (pafolacianine) injection for intraoperative imaging of ovarian cancer. News release. September 12, 2022. Accessed September 12, 2022.
  3. FDA approves pafolacianine for identifying malignant ovarian cancer lesions. News release. December 1, 2021. Accessed September 12, 2022.
  4. On Target Laboratories announces FDA approval of Cytalux™ (pafolacianine) injection for identification of ovarian cancer during surgery. News release. November 29, 2011.
  5. Randall LM, Wenham RM, Low PS, Dowdy SC, Tanyi JL. A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer. Gynecol Oncol. 2019;155(1):63-68. doi:10.1016/j.ygyno.2019.07.010