Clinical benefits of early-phase clinical trials for rare malignancies: Asian single-center analysis.

Abstract

e15202 Background: The available chemotherapies for patients with rare malignancies are limited. Enrollment in early-phase clinical trials (EPCTs) is a promising approach to expand treatment options. However, clinical data about the venue of EPCTs remains scarce worldwide. Methods: Medical records of 1,291 patients referred to our department between 2021-2025 were reviewed. Based on the Rare Cancers in Europe definition, we categorized respective patient as having either a rare malignancy, with annual incidence of < 6 per 100,000 people per year or a common malignancy. We analyzed the patient backgrounds, enrollment status in EPCTs, and clinical outcomes. The trial enrollment rate was calculated as follows: the number of patients who received some investigational drug at least once divided by the number of patients referred to our department. We further defined an ultra-rare malignancy as having an incidence of < 0.2 per 100,000 people per year in a rare malignancy group and examined the enrollment status. Results: A rare malignancy accounted for 43% of all analyzed cases. The most frequently represented cancer types included in this group were ovarian cancer (n = 146), biliary tract cancer (n = 74), esophageal cancer (n = 57), and sarcoma (n = 49). Patients with common malignancies was heavily treated before trial enrollment than those with rare malignancies (average 2.7 regimens, range 0-15 vs. 2.3 regimens, range 0-10). The enrollment rate in EPCTs was similar (31% vs. 28%) for the two groups. The rates for representative cancer types as follows: 42% for ovarian cacer, 16% for biliary tract cancer, 37% for esophageal cancer, 29% for sarcoma, 34% for cervical cancer, and 43% for head and neck cancer. Remarkably, three patients with rare malignancy (two with ovarian cancer and one with cervical cancer) received three investigational drugs. The overall response rate (ORR) in the rare malignancy and common malignancy groups was 25% and 18%, respectively. Median progression-free survival in the both groups was 3.0 and 2.3 months, respectively. The ORR varied among cancer types (37% for ovarian cancer; 35% for esophageal cancer; 17% for head and neck cancer; 6% for cervival cancer; 0% for biliary tract cancer; 0% for sarcoma). Of the 88 patients with ultra-rare malignancies, 24 patients (27%) were enrolled, including those with ovarian cancer (n = 12), melanoma (n = 3), sarcoma (n = 3), and endometrial cancer (n = 3). The ORR was 26%. Conclusions: Our analysis suggests that patients with rare malignanicies as a whole had comparable clinical benefits from EPCT enrollment as those with common malignancies. However, tumor response was various among types of cancer, partly due to their different biological behaviors. Our data confirm that ovarian cancer is a promising target, as multiple EPCTs are underway. Concurrently, there is an urgent need for clinical development of rare entities such as sarcoma and biliary tract cancer.