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.

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.
Competing Interests: Conflict of interest statement A.K., J.W., J.S., M.B., S.B., H.R and U.P. declare no conflicts of interest. D.P.M.: Honoraria: Amgen, Roche, Servier, Bristol-Myers Squibb, Pfizer, Taiho Pharmaceutical, Merck Sharp & Dohme. Consulting or Advisory Role: Merck Serono, Amgen, Merck Sharp & Dohme, Roche, Servier, Bristol-Myers Squibb. Research Funding (Institutional): Merck Serono (Inst), Roche (Inst), Amgen (Inst). Travel, Accommodations, Expenses: Amgen, Merck Serono, Bayer HealthCare Pharmaceuticals, Servier, Bristol-Myers Squibb, Roche. H.O.: Honoraria: Servier, Bristol-Myers Squibb. Consulting or Advisory Role: Servier, Bristol-Myers Squibb. Research Funding (Institutional): Bristol-Myers Squibb. Travel, Accommodations, Expenses: Bristol-Myers Squibb. S.K.: Honoraria: Miltenyi Biotec, Fresenius Kabi. Travel, Accommodations, Expenses: Bristol-Myers Squibb, Gilead. M.S.: Honoraria: Sanofi, Astra Zeneca, Leo Pharma, Amgen, Pfizer, Servier, Incyte, MCI, IKF Frankfurt. Consulting or Advisory Role: Merck Serono, Amgen, Merck Sharp & Dohme, Roche, Servier, Bristol-Myers Squibb. Research Funding (Institutional): Leo Pharma, Servier, MSD, Astra Zeneca, Incyte, Boston medical, BMS. Travel, Accommodations, Expenses: Servier.
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