Hepatectomy Plus Chemotherapy or Chemotherapy Alone for Resectable Liver and Unresectable Lung Metastases from Colorectal Adenocarcinoma (LUNA): A Randomized Phase II Trial.

Abstract

Hepatectomy for isolated colorectal liver metastases is associated with 5 year overall survival (OS) of 58% and is accepted as standard of care. However, the role of liver resection with unresectable low-volume lung metastases is unknown. LUNA was a phase II randomized trial designed to study the survival benefit of hepatectomy with unresectable lung metastases. After stratification by KRAS status and primary tumor in the colon versus rectum, patients were randomized 1:1 to hepatectomy plus chemotherapy or chemotherapy alone. The primary endpoint was 3 year OS. Slow accrual led to early trial closure. In total, 29 patients were enrolled and 27 randomized to either the experimental hepatectomy group (n=10) or the control group of chemotherapy alone (n=17), comprising the intention-to-treat population. Three patients in the chemotherapy group crossed over to surgery, and five in the hepatectomy group crossed over to standard treatment. Thus, the as-treated population comprised eight patients who underwent surgery and 19 who were treated with chemotherapy alone. Intention-to-treat analysis demonstrated 3-year OS of 30% (95% confidence interval [CI] 12‒77) and 34% (95% CI 17-67) in the surgery and control arms, respectively (p=0.53). In the as-treated analysis, hepatectomy was associated with significantly higher 3 year OS than chemotherapy alone (75% [95% CI 50-100] vs 16% [95% CI 6-45], p = 0.001). LUNA is the first randomized study to evaluate the potential benefit of hepatectomy for patients with colorectal cancer with resectable liver and unresectable low-volume lung metastases. The trial was closed early and did not meet the primary endpoint. Findings from the as-treated analysis may warrant validation in a larger, multicenter cohort.