Pafolacianine was discussed in an article highlighting the Food and Drug Administration (FDA) approval for use as an imaging drug to identify ovarian cancer lesions during surgery via fluorescent imaging. Pafolacianine is administered approximately one hour prior to surgery and binds to folate receptors, which are typically overexpressed in ovarian cancer. A phase 3 trial (summarized in Table 1) paved the way for its approval. [1]
Pafolacianine, under the research name OTL38, has been studied in a variety of investigational settings as an imaging tool to identify certain cancer types or to assist in surgical removals. These include but are not limited to lung cancer, laparoscopic partial nephrectomy, resection of pulmonary lesions, etc. The majority of studies describe pafolacianine as safe and effective in achieving the desired outcome, though these studies are primarily performed without a control group. These early studies also focus on sensitivity/specificity value during identification procedures or successful extraction during surgical procedures. [2], [3], [4], [5], [6]
A recently published meta-analysis evaluating fluorescence-guided surgery to detect microscopic disease in ovarian cancer found that the pooled odds ratio (OR) for a change in surgical plan based on folate receptor studies (e.g., pafolacianine) was 1.29 (95% confidence interval [CI] 1.13 to 1.44). Subgroup analyses found that folate receptor-based agents had a pooled sensitivity of 84% but varied across studies with a high degree of heterogeneity (I2= 91.2%). Similarly, aminolevulinic acid (5-ALA) also resulted in a sensitivity of 84%. The pooled specificity of 26% for folate receptor agents suggests these agents have a low ability to detect true negatives, with a high false-positive rate. In contrast, 5-ALA was found to have a much higher specificity of 96%, with a low degree of heterogeneity across studies. The pooled positive predictive values (PPV) for folate receptor agents was 0.76 compared to 0.96 with 5-ALA. Again, PPV results were highly variable across studies for pafolacianine. The authors determined that 5-ALA was the best agent with respect to sensitivity, specificity, and PPV. Studies found that fluorescence tracers using pafolacianine had an acceptable safety profile with the most common side effects including nausea, vomiting, and abdominal discomfort; no adverse events were reported for 5-ALA. [7]