Repeated adjuvant anti-CEA radioimmunotherapy after resection of colorectal liver metastases: Safety, feasibility, and long-term efficacy results of a prospective phase 2 study.

Abstract

In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) ¹³¹ I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m² per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and ¹⁸ F-fluorodeoxyglucose-positron emission to confirm that patients were "truly adjuvant." Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as "possibly nonadjuvant," but they also received RIT. Time to progression (TTP), overall survival (OS), and cause-specific survival (CSS) were calculated. The median follow-up was 54 months. After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The "truly adjuvant" patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P < .001), OS (75.6 vs 33.4 months; hazard ratio, 0.44; P = .014), and CSS (not reached vs 41.4 months; hazard ratio,0.42; P = .014) compared with "possibly nonadjuvant" patients (N = 24). Repeated RIT with ¹³¹ I-labetuzumab is feasible but is associated with hematotoxicity. Survival is very encouraging, especially for "truly adjuvant" patients. However, the maximum safe dose of ¹³¹ I-labetuzumab is a single administration of 50 millicuries/m² . Cancer 2017;123:638-649. © 2016 American Cancer Society.