Impact of completeness of adjuvant gemcitabine, relapse pattern, and subsequent therapy on outcome of patients with resected pancreatic ductal adenocarcinoma - A pooled analysis of CONKO-001, CONKO-005, and CONKO-006 trials

Eur J Cancer. 2021 Jun:150:250-259. doi: 10.1016/j.ejca.2021.03.036. Epub 2021 Apr 30.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) represents one of the most fatal malignancies worldwide. It is suggested that survival in PDAC depends, among other things, on pattern of disease recurrence.

Patients and methods: We performed a pooled analysis of the adjuvant therapy studies CONKO-001, CONKO-005, and CONKO-006, including a total of 912 patients with regard to prognostic factors in patients with recurrent disease. Overall survival from disease recurrence (OS 2) and disease-free survival (DFS) from the day of surgery were expressed by Kaplan-Meier method and compared using log-rank testing and Cox regression.

Results: Of 912 patients treated within the previously mentioned CONKO trials, we identified 689 patients with disease recurrence and defined site of relapse. In multivariable analysis, the presence of isolated pulmonary metastasis, low tumour grading, and low postoperative level of CA 19-9 remained significant factors for improved OS 2 and DFS. Furthermore, completeness of adjuvant gemcitabine-based treatment (OS 2: P = 0.006), number of relapse sites (OS 2: P = 0.015), and type of palliative first-line treatment (OS 2: P < 0.001) significantly affected overall survival after disease recurrence in PDAC.

Conclusions: Determining tumour subgroups using prognostic factors may be helpful to stratify PDAC patients for future clinical trials. In case of disease recurrence, the site of relapse may have a prognostic impact on subsequent survival. Further investigations are needed to identify differences in tumour biology, reflecting relapse patterns and the differing survival of PDAC patients.

Keywords: Liver metastasis; Lung metastasis; Metastatic pancreatic cancer; Overall survival; Relapse patterns.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Tumor-Associated, Carbohydrate / blood
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Carcinoma, Pancreatic Ductal / blood
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / secondary
  • Carcinoma, Pancreatic Ductal / therapy*
  • Chemotherapy, Adjuvant
  • Databases, Factual
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Palliative Care
  • Pancreatectomy* / adverse effects
  • Pancreatectomy* / mortality
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Young Adult

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Antimetabolites, Antineoplastic
  • carbohydrate antigen 199, human
  • Deoxycytidine
  • Gemcitabine