V38: Defining Effective Neoadjuvant Chemotherapy (NAC) in PDAC, Implications from Survival and Pattern of Failure in Patients Who Received NAC

Wednesday, March 2, 2022

5:28 PM – 5:31 PM CST

Location: Zoom Meeting

Virtual Poster Presenter(s)

Hao Liu, MD PhD

Resident Physician
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States

Disclosure: Disclosure information not submitted.

Participants should be aware of the following financial/non-financial relationships:

Hao Liu, MD PhD: Disclosure information not submitted.

Introduction:

Neoadjuvant chemotherapy (NAC) is gaining popularity over the surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy in resectable or borderline resectable PDAC patients is unknown.

Methods:

We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier, multivariate-adjusted Cox models, Propensity score methods and and competing risk subdistribution methods for statistical analysis. Overall survival (OS) was calculated from both diagnosis and surgery to account for the immortal time bias of receiving NAC.

Results:

586 patients were included in this study. The multivariate-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR=0.77, p=0.021), but not from surgery (HR=0.89, p=0.312). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3m vs. 21.5m, p=0.005) or the 117 SF patients (39.3m vs. 19.5m, p< 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients in both unadjusted and multivariate-adjusted models, even when calculating OS from diagnosis (HR=0.86, p=0.378).

Liver metastasis was significantly reduced in patients with optimal CA19-9 response to NAC (HR 0.41, p=0.02). However, lung metastasis was not affected, even with optimal CA19-9 response. There is also no significant reduction in peritoneal metastatic progression or local recurrence reduction, even with optimal CA19-9 response.

Conclusions:

We identified a CA19-9 response to NAC of “normalization AND >50% reduction” as the marker for effective NAC. Suboptimal CA19-9 NAC responses did not correlate with a survival benefit compared to the SF approach, even when accounting for the NAC immortal-time bias. However, optimal CA19-9 is associated with longer survival with a significant reduction in metastatic progression in the liver, but not other sites. This result should be verified in a multi-institutional study.

Learning Objectives:

Upon completion, participant will be able to recall that response to neoadjuvant chemotherapy measured by CA19-9 response has a wide range of heterogeneity.
Upon completion, participant will be able to know that CA19-9 change threshold of "normalization AND >50% drop" associated with neoadjuvant chemotherapy is associated with longer overall survival and disease-free survival
Upon completion, participant will be able to know that CA19-9 change threshold of "normalization AND >50% drop" associated with neoadjuvant chemotherapy is associated with a change in treatment failure pattern