Effect of Adjuvant Chemotherapy on Survival in Patients With Resected Pancreatic Adenocarcinoma After Multiagent Neoadjuvant Chemotherapy

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In a retrospective matched-cohort study reported in JAMA Oncology, Sugawara et al found that receipt of adjuvant chemotherapy improved survival vs no adjuvant chemotherapy in patients with pancreatic adenocarcinoma who received curative-intent surgery following multiagent neoadjuvant chemotherapy.

Study Details

The analysis used data from the National Cancer Database on patients diagnosed with pancreatic adenocarcinoma between 2010 and 2018. Propensity score–matched cohorts of 444 patients who received adjuvant chemotherapy and 444 who did not were derived by matching for age, sex, facility type, Charlson-Deyo comorbidity index score, tumor location, preoperative CA 19-9 level, pathologic T and N category, margin status, and tumor differentiation. The main outcome measure was overall survival in the adjuvant chemotherapy group vs the non–adjuvant chemotherapy group.

Key Findings

Median follow-up after surgery was 21.3 months (interquartile range [IQR] = 12.3–33.4 months). Median overall survival was 26.6 months (IQR = 22.5–29.6 months) in the adjuvant chemotherapy group vs 21.2 months (IQR = 17.1–24.5 months) in the non–adjuvant chemotherapy group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.65–0.91, P = .002). Rates at 1 and 5 years were 76.3% vs 65.3% and 22.2% vs 20.2%, respectively. On multivariate analysis, the hazard ratio in favor of the adjuvant chemotherapy group was 0.71 (95% CI = 0.59–0.85, P < .001).

In subgroup analyses, the overall survival benefit of adjuvant chemotherapy vs no adjuvant chemotherapy varied according to age, pathologic T category, and tumor differentiation. Improvement was significant for:

  • Patients aged ≤ 64 years (HR = 0.76, 95% CI = 0.60–0.97) and 65 to 74 years (HR = 0.64, 95% CI = 0.48–0.85)
  • Disease stages ypT3 (HR = 0.76, 95% CI = 0.62–0.93) and ypT4 (HR = 0.30, 95% CI = 0.11–0.79)
  • Moderately differentiated (HR = 0.71, 95% CI = 0.57–0.89) and poorly differentiated tumors (HR = 0.62, 95% CI = 0.46–0.84).

In contrast, adjuvant chemotherapy was associated with significant benefit in any pathologic N category and positive margin status; ie: stages ypN0 (HR = 0.68, 95% CI = 0.51–0.92) and ypN1 (HR = 0.72, 95% CI = 0.58–0.90), and R1 (HR = 0.56, 95% CI = 0.35–0.92) and R2 resection (HR = 0.06, 95% CI = 0.01–0.50) as well as in R0 resection (HR = 0.74, 95% CI = 0.61–0.90).

The investigators concluded: “In this cohort study, adjuvant chemotherapy following multiagent neoadjuvant chemotherapy and resection in patients with pancreatic adenocarcinoma was associated with significant survival benefit compared with that in patients who did not receive adjuvant chemotherapy. These findings suggest that patients with aggressive tumors may benefit from adjuvant chemotherapy to achieve prolonged survival, even after multiagent neoadjuvant chemotherapy and curative-intent resection.”

Marco Del Chiaro, MD, PhD, of the Division of Surgical Oncology, University of Colorado School of Medicine, Aurora, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the Japan Society for the Promotion of Science Overseas Challenge Program for Young Researchers and Mochida Memorial Foundation for Medical and Pharmaceutical Research. For full disclosures of the study authors, visit

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