AGGRESSIVE MANAGEMENT OF ELDERLY PATIENTS WITH NON-METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
Zhi Ven Fong*, Fidel Lopez Verdugo, Carlos Fernandez-Del Castillo, Cristina R. Ferrone, Jill N. Allen, Lawrence S. Blaszkowsky, Jeffrey Clark, Aparna Parikh, David P. Ryan, Colin D. Weekes, Theodore S. Hong, Jennifer Y. Wo, Keith D. Lillemoe, Motaz Qadan
Surgery, Massachusetts General Hospital, Boston, MA
Introduction
Older patients constitute the majority of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), but remain underrepresented in clinical trials. In addition, aggressive neoadjuvant treatment approaches may be associated with higher toxicity and lower tolerability rates. This study aimed to assess the efficacy of neoadjuvant FOLFIRINOX in older patients with non-metastatic PDAC, which remain poorly defined.
Methods
Patients with non-metastatic PDAC who were initiated on FOLFIRINOX (intent-to-treat analysis) from 2015 to 2020 were identified from our institution's pharmacy records, including patients who did not undergo eventual operative exploration. Patients were divided into 2 groups for analysis, with older patients being >=75 years old and younger patients defined as <75 years old.
Results
A total of 254 patients with non-metastatic PDAC were initiated on FOLFIRINOX, of whom 40 (15.7%) were >=75 years old. Major toxicity (grades 3 and 4) rates were similar between older patients and younger patients (57.5% vs. 40.2%, p=0.18). However, older patients experienced higher rates of toxicity-related emergency room visits (52.5% vs. 24.8%, p<0.001) and inpatient admissions (57.5% vs. 35.9%, p=0.015) compared with younger counterparts. The median length of hospital stay for toxicity-related admissions was also higher in the older cohort (7 days vs. 3 days, p=0.018).
A lower proportion of older patients were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (65.0% vs. 81.4%, p=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, p=0.89) as well as surgical resection (57.5% vs 55.6%, p=0.70).
There was no statistically significant difference in the median overall survival (OS) between older patients and younger patients (2.8 years vs. 2.7 years, p=0.858; Figure 1) in this neoadjuvant intent-to-treat analysis. Adjusted predictors of worse OS included not undergoing surgical exploration, ECOG performance status >=1 at diagnosis, and tumor size at diagnosis, but not age or inability to complete intended systemic chemotherapy cycles.
Conclusions
Older patients with non-metastatic PDAC initiated on FOLFIRINOX with curative-intent experienced more toxicity-related emergency room visits and inpatient admissions and were less likely to complete their chemotherapy cycles when compared to younger patients. However, they were just as likely to undergo surgical exploration and resection and had similar adjusted survival outcomes when compared to younger patients, highlighting the feasibility of aggressive management of PDAC in elderly patients, including the use of neoadjuvant FOLFIRINOX.
Figure 1. Kaplan-Meier curve depicting the overall survival outcomes for patients >=75 years old and <75years old with non-metastatic pancreatic adenocarcinoma who were initiated on neoadjuvant FOLFIRINOX therapy with curative-intent.
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