47: Chemotherapy Dose Density is Prognostic for Patients with Resectable Pancreas Cancer: A Secondary Analysis of SWOG S1505

Thursday, March 21, 2024

2:52pm – 3:02pm ET

Location: C101

Abstract Presenter(s)

Sameer H. Patel, MD, FSSO (he/him/his)

Associate Professor
Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, United States, United States

Submitter(s)

Sameer H. Patel, MD, FSSO (he/him/his)

Associate Professor
Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, United States, United States

Author(s)

Sameer H. Patel, MD, FSSO (he/him/his)

Associate Professor
Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, United States, United States
SC

Sarah Colby, PhD

SWOG Statistical and Data Management Center
Fred Hutchinson Cancer Center, United States
DS

Davendra Sohal, MD

Medical Oncology
University of Cincinnati College of Medicine, United States
KG

Katherine Guthrie, PhD

SWOG Statistical and Data Management Center
Fred Hutchinson Cancer Center, United States
LK

Lisa Kachnic, MD

Radiation Oncology
Columbia University Irving Medical Center, United States
GC

Gabriela Chiorean, MD

Medical Oncology
University of Washington, United States
AL

Andrew M. Lowy, MD

Professor Surgery
Department of Surgery, Division of Surgical Oncology, University of California, San Diego, United States
Flavio G. Rocha, MD

Professor
Oregon Health & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Portland, OR 97239 USA
Portland, Oregon, United States
PP

Philip Philip, MD

Medical Oncology
Wayne State University Henry Ford Cancer Institute, United States
Syed A. Ahmad, MD (he/him/his)

Professor of Surgery, Director University of Cincinnati Cancer Center
University of Cincinnati Cancer Center
Cincinnati, Ohio, United States

Disclosure(s):

Sameer H. Patel, MD, FSSO: No financial relationships to disclose

Syed A. Ahmad, MD: No financial relationships to disclose

Introduction: Chemotherapy is an integral part of multimodality treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Assessing the impact of chemotherapy dose reductions or missed cycles on survival is difficult as few trials address the prognostic value of this important metric.

Methods: SWOG S1505 (NCT02562716) was a randomized, phase II study of perioperative chemotherapy with mFOLFIRINOX or gemcitabine/nab-paclitaxel for resectable PDAC. Dose density (DD) was defined as estimated percent of chemotherapy dose received of the total planned, thresholds were based on published analyses and balance in sample size across treatment arms. Cox regression analysis of overall survival (OS) according to DD was performed in patients alive at two landmark time points: after surgery (among those who completed surgery) and at 40 weeks (when protocol therapy was to be completed).

Results: Of the 103 eligible patients enrolled, median age was 64 years old, 81% underwent pancreaticoduodenectomy, 15% distal pancreatectomy, and 3% a total pancreatectomy. In the 73 patients who underwent surgery, median neoadjuvant chemotherapy DD was 89%. Patients with ≥ 85% DD had higher median OS from surgery (38.1 v. 17.2 months, p=0.039, Figure A) compared to patients with < 85% DD. Of the 82 patients who survived to 40 weeks post randomization, 67 underwent surgery and 58 started adjuvant chemotherapy. The median DD for all perioperative chemotherapy was 67%; DD was significantly higher for neoadjuvant compared to adjuvant therapy (83% vs. 58%, p< 0.001). In this cohort, DD ≥ 70% was associated with better median OS from 40 weeks post randomization (32.2 v. 14.0 months, p=0.017, Figure B). DD was not significantly associated with pathologic response, margin status, or lymph node negativity.

Conclusions:

This is the first study to identify a prognostic association of chemotherapy dose density with OS in patients undergoing perioperative chemotherapy and surgery for resectable PDAC. S1505 participants who received ≥ 85% DD preoperatively and/or ≥70% DD perioperatively had significantly higher OS than those receiving a smaller proportion of protocol therapy. These findings suggest that DD should be evaluated in future prospective studies for PDAC and could be used to determine the optimal quantity of therapy patients should receive. Moreover, given that greater survival benefit is achieved with higher chemotherapy DD, and higher DD is more likely in the preoperative vs. postoperative period, these data support consideration of a neoadjuvant approach for resectable PDAC.

Learning Objectives:

Upon completion, participants will be able to describe the importance of dose density chemotherapy as a prognostic factor for patients undergoing surgery for resectable pancreas adenocarcinoma.
Upon completion, participants will be able to list the dose density thresholds of chemotherapy to achieve a survival benefit in patients undergoing surgery for resectable pancreas adenocarcinoma.
Upon completion, participants will be able to describe why the neoadjuvant approach for chemotherapy in patients with resectable pancreas adenocarcinoma is associated with achieving higher dose densities.