Adjuvant Chemo After Neoadjuvant Chemo/Surgery Linked With Survival in PDAC

The use of adjuvant chemotherapy following multiagent neoadjuvant chemotherapy and curative-intent surgery in patients with pancreatic ductal adenocarcinoma was associated with a significant survival benefit, according to findings from a retrospective study published in JAMA Oncology.

"The results of this study warrant [randomized clinical trials] to evaluate the true benefit of [adjuvant chemotherapy]" among patients with pancreatic ductal adenocarcinoma "to make evidence-based recommendations," according to authors of a study published in JAMA Oncology.

The median overall survival (OS) for patients who received adjuvant chemotherapy was 26.6 months (interquartile range [IQR], 22.5-29.6) vs 21.2 months (IQR, 17.1-24.5; P = .002) for those who did not receive adjuvant chemotherapy following neoadjuvant chemotherapy (HR, 0.77; 95% CI, 0.65-0.91). The OS rates for each respective group were 76.3% (95% CI, 72.0%-80.0%) vs 65.3% (95% CI, 60.6%-69.6%) at 1 year, and 22.2% (95% CI, 16.7%-28.2%) vs 20.2% (95% CI, 15.6%-21.2%) at 5 years, respectively.

A multivariate Cox regression model adjusting for all covariates identified an association between adjuvant chemotherapy and improved survival for patients with pancreatic ductal adenocarcinoma compared with those who did not receive adjuvant chemotherapy (HR, 0.71; 95% CI, 0.59-0.85; P <.001).

“The results of this study warrant [randomized clinical trials] to evaluate the true benefit of [adjuvant chemotherapy] in this setting to make evidence-based recommendations,” the study authors stated.

Investigators of the retrospective, matched-cohort study used data from the National Cancer Database, including patients who were diagnosed with pancreatic ductal adenocarcinoma from 2010 and 2018. Patients were sorted into 2 major groups based on whether they had received adjuvant chemotherapy following multiagent neoadjuvant chemotherapy and curative surgery.

The main end point of the study was OS of patients who received adjuvant chemotherapy compared with those who did not. Investigators explored interactions between adjuvant chemotherapy and pathological findings based on multivariate Cox regression models that adjusted for factors including age, sex, facility type, tumor location, margin status, and year of diagnosis.

Patients 18 years and older who received multiagent neoadjuvant chemotherapy and surgical resection for pancreatic ductal adenocarcinoma were included in the study. Patients with clinical or pathological stage IV disease or who died within 90 days of operation were excluded from the study.

Of 9206 patients with pancreatic ductal adenocarcinoma who received curative-intent resection, 1132 received multiagent neoadjuvant chemotherapy. Following 1:1 propensity score matching, investigators included a total of 444 patients who received adjuvant chemotherapy and 444 who did not.

In the population of patients who received multiagent neoadjuvant chemotherapy, the mean patient age was 63.5 years (standard deviation, 9.4), and most patients were male (51.0%). In the matched data set, most patients in the adjuvant chemotherapy and non-adjuvant chemotherapy groups had a Charlson-Deyo comorbidity index score of 0 (67% and 67%), had a primary site in the head (84% and 85%), had ypT3 disease (70% and 69%), and had ypN1 disease (61% and 62%).

In subgroup interaction analyses, investigators associated the use of adjuvant chemotherapy with significantly lower mortality in patients younger than 75 years, those with a pathological T category of ypT3 or greater, and patients with moderately or poorly differentiated tumors. The associated benefits of adjuvant chemotherapy were observed regardless of pathological N category and margin status.

The only interaction in the subgroup analysis that did not favor the use of adjuvant chemotherapy was among patients with well-differentiated tumors. In this subgroup, the median survival time was 36 months (IQR, 25-80) among patients who received adjuvant chemotherapy vs 27 months (IQR, 17-43) among those who did not (adjusted HR, 1.09; 95% CI, 0.62-1.90).

Reference

Sugawara T, Franco SR, Sherman S, et al. Association of adjuvant chemotherapy in patients with resected pancreatic adenocarcinoma after multiagent neoadjuvant chemotherapy. JAMA Oncol. Published December 8, 2022. doi:10.1001/jamaoncol.2022.5808