The United States Food and Drug Administration (FDA) granted approvals for two cancer treatments and a folate receptor-targeting fluorescent imaging agent.

• Pembrolizumab for Adjuvant Treatment of Renal Cell Carcinoma. Approval was granted to pembrolizumab (Keytruda®, Merck) for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. The approval was based on efficacy results from the multicenter, randomized, double-blind, placebo-controlled, phase III KEYNOTE-564 trial, in which patients were randomized to receive either pembrolizumab or placebo for up to 1 year until disease recurrence or unacceptable toxicity. At the prespecified interim analysis, pembrolizumab treatment resulted in a significant improvement in disease-free survival (DFS) compared with placebo: DFS at 24 months was 77.3% vs. 68.1%, respectively (hazard ratio [HR] for recurrence or death: 0.68; P = 0.002). Median DFS was not reached in either arm. At the time of the DFS analysis, overall survival data were not mature, with 5% deaths in the overall population.

• Sirolimus Protein-Bound Particles for Malignant Perivascular Epithelioid Cell Tumor. Sirolimus protein-bound particles for injectable suspension (Fyarro™, Aadi Bioscience, Inc.) is the first and only approved therapy for patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa), an extremely rare and aggressive form of sarcoma. Efficacy results from the multicenter, single-arm, phase II AMPECT trial supported the approval. In total, 31 patients received sirolimus protein-bound particles at 100 mg/m² on days 1 and 8 of each 28-day cycle until disease progression or unacceptable toxicity. The overall response rate (ORR) was 39%, which included one complete response (CR). Median duration of response (DoR) was not reached after a median follow-up of 2.5 years. Among responders, 67% had a response lasting more than 12 months and 58% had a response lasting greater than 24 months.

• Pafolacianine for Identifying Malignant Ovarian Cancer Lesions. Approval was granted to folate receptor-targeting fluorescent imaging agent pafolacianine (Cytalux™, On Target Laboratories, LLC), for patients with ovarian cancer as an adjunct for interoperative identification of malignant lesions. Pafolacianine is administered as a 1-hour intravenous injection, and after binding to folate receptors, which are expressed in most patients with epithelial ovarian cancer, lesions illuminate intraoperatively under near-infrared light. A near-infrared fluorescence (NIRF) imaging system has been cleared by the FDA for specific use with pafolacianine. Supporting this approval were efficacy data from a single-dose, multicenter, open-label, phase III trial. As part of the trial, pafolacianine was administered to patients diagnosed with ovarian cancer who were scheduled to undergo primary surgical cytoreduction. Results showed that 33% of patients had additional lesions for resection identified by NIRF imaging with pafolacianine that were not detected by normal white light and palpation (P<0.001). In patients who underwent interval debulking surgery the rate was higher, at 39.7% of patients. The sensitivity of pafolacianine with NIRF to detect ovarian cancer was 83% at the individual lesion level, with a false-positive rate of 32.7%. Investigators reported achieving complete resection (R0) in 62.4% of patients.