Association of Adjuvant Chemotherapy in Patients With Resected Pancreatic Adenocarcinoma After Multiagent Neoadjuvant Chemotherapy

Abstract

ImportanceThe total number of patients with pancreatic ductal adenocarcinoma (PDAC) who receive neoadjuvant chemotherapy (NAC) is increasing. However, the added role of adjuvant chemotherapy (AC) in these patients remains unknown.ObjectiveTo evaluate the association of AC with overall survival (OS) in patients with PDAC who received multiagent NAC followed by curative-intent surgery.Design, Setting, and ParticipantsThis retrospective, matched-cohort study used data from the National Cancer Database and included patients with PDAC diagnosed between 2010 and 2018. The study included patients at least 18 years of age who received multiagent NAC followed by surgical resection and had available records of the pathological findings. Patients were excluded if they had clinical or pathological stage IV disease or died within 90 days of their operation.ExposuresAll included patients received NAC and underwent resection for primary PDAC. Some patients received adjuvant chemotherapy.Main Outcomes and MeasuresThe main outcome was the OS of patients who received AC (AC group) vs those who did not (non-AC group). Interactions between pathological findings and AC were investigated in separate multivariable Cox regression models.ResultsIn total, 1132 patients (mean [SD] age, 63.5 [9.4] years; 577 [50.1%] male; 970 [85.7%] White) were included, 640 patients in the non-AC group and 492 patients in the AC group. After being matched by propensity score according to demographic and pathological characteristics, 444 patients remained in each group. The multivariable Cox regression model adjusted for all covariates revealed an association between AC and improved survival (hazard ratio, 0.71; 95% CI, 0.59-0.85; P < .001). Subgroup interaction analysis revealed that AC was significantly associated with better OS (26.6 vs 21.2 months; P = .002), but the benefit varied by age, pathological T category, and tumor differentiation. Of note, AC was associated with better survival in patients with any pathological N category and positive margin status.Conclusions and RelevanceIn this cohort study, AC following multiagent NAC and resection in patients with PDAC was associated with significant survival benefit compared with that in patients who did not receive AC. These findings suggest that patients with aggressive tumors may benefit from AC to achieve prolonged survival, even after multiagent NAC and curative-intent resection.

Pancreatic cancer: the insidious, deadly malignancy

“…Of these, 492 patients also received adjuvant chemotherapy. Controls did not receive adjuvant chemotherapy 10 …”

Adjuvant Therapy for Pancreatic Adenocarcinoma—Leaving No Rock Unturned

“…Relating to the internal validity of the primary study finding, while the authors’ conclusion that adjuvant chemotherapy following neoadjuvant therapy and surgery is associated with a survival benefit is supported by their data and analyses, at least 3 known limitations of the NCDB increase the risk of selection bias and affect the way we should view these findings. First, the NCDB does not contain information on the number of cycles of chemotherapy each patient receives, details relating to the chemotherapy regimen used, and importantly cannot distinguish whether patients treated with adjuvant chemotherapy received a multiagent or single-agent regimen.…”

“…In this issue of JAMA Oncology , Sugawara et al present the findings from an observational, propensity-matched analysis using National Cancer Database (NCDB) data to evaluate this exact question. In their analysis, they identified a survival benefit among patients who received neoadjuvant multiagent chemotherapy followed by surgical resection and adjuvant chemotherapy—notably, this benefit was consistent among multiple subgroups relating to age, pathologic T category, tumor grade, lymph node status, and resection margin.…”

“…An equally important issue to consider is whether different variations of questions regarding the use of adjuvant therapy in the management of patients with PDAC treated with neoadjuvant therapy are still clinically important. Admittedly, this remains an area of some ambiguity and therefore the question addressed by Sugawara et al does have merit. But, rather than continuing to focus on how and when postoperative systemic therapy can and should be used in the management of patients with PDAC, might it not be more prudent, and is it not time to have an informed debate about a different question altogether?…”

“…For example, some patients may not be able to tolerate neoadjuvant chemotherapy because of gastric outlet obstruction or an inability to maintain hydration and/or nutrition. For these patients, the current work from Sugawara and colleagues suggests this may be an effective way to administer multimodal therapy. But this likely represents the minority of patients.…”