Chemotherapy dose density is prognostic for overall survival in patients with resectable pancreas cancer: A landmark analysis of SWOG 1505.

Abstract

Chemotherapy is required to improve the overall survival (OS) of patients with resectable pancreatic ductal adenocarcinoma (PDAC). Assessing the impact of chemotherapy dose density (DD) on survival is difficult as a result of confounding. The objective of this study was to determine the impact of chemotherapy DD on OS in patients with resectable PDAC. This was a secondary analysis of SWOG 1505, a randomized phase 2 trial of perioperative chemotherapy in resectable PDAC. DD was defined as the percentage of chemotherapy dose received of the total planned. Two landmark time points for OS were used: after surgery and at 40 weeks (which encompassed the entire treatment period). Of the 102 eligible patients enrolled, 73 (71%) underwent surgery, and median preoperative chemotherapy DD was 89%. Patients with ≥85% DD had higher OS compared to those with <85% DD (median, 38.1 vs. 17.2 months; p = .039). Of the 82 patients who survived to 40 weeks postrandomization, 67 underwent surgery, and median DD for all perioperative chemotherapy was 67%. In this cohort, DD ≥70% was associated with better OS (median, 32.2 vs. 14.0 months; p = .017). Perioperative DD was not significantly associated with pathologic response, margin status, or lymph node negativity. This is the first study to identify a prognostic association of chemotherapy DD with OS in patients undergoing perioperative chemotherapy and surgery for resectable PDAC. Patients who received ≥85% DD preoperatively and/or ≥70% DD perioperatively survived longer than those receiving a smaller proportion of protocol therapy.