Abstract
Background
Defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma (PDAC) receiving primary chemotherapy is an unmet need. The role of time to CA19-9 nadir and of nadir magnitude was explored in this study.
Patients and methods
The databases of our institution’s prospective trials were queried to speculate on the time to maximum chemotherapy response. Patients with pathologically proven, metastatic (N = 356) or non-metastatic non-resected (N = 163) PDAC and elevated baseline (> 34 UI/mL) CA19-9 were analyzed. Survival curves were estimated using the Kaplan–Meier method and compared by means of the log-rank test for analyses including at least 45 patients. Multivariable Cox proportional hazards model was used to estimate clinical features for their association with OS. All probability values were from two-sided tests.
Results
Time to CA19-9 nadir was ≥ 4 months in 184 of 346 (53%) metastatic and 121 of 163 (74%) non-metastatic patients (p = 0.002). The likelihood of a later nadir was higher with taxane-based chemotherapy as compared to taxane-free combinations (73% versus 56%; p = 0.02). Both metastatic and non-metastatic patients had significantly longer survival when nadir occurred later. Patients with a larger CA19-9 nadir magnitude had significantly longer survival. Metastatic patients with CA19-9 reduced by < 50%, 50–89%, or > 89% and had a median survival of 7.4, 9.8, and 14.7 months, respectively (p ≤ 0.001 for all comparisons). The corresponding figures for non-metastatic patients were 10.6; 17.0; and 18.7 months, respectively (p ≤ 0.02 for < 50% versus 50–89% or > 89%; p = 0.14 for 50–89% versus > 89%). Multivariable analyses showed that time to CA19-9 nadir but not CA19-9 nadir magnitude was independently predictive of survival.
Conclusion
The present study suggests that a 4–6 months program might be a more suitable candidate for prospective assessment in comparison to shorter pre-defined period in patients who are candidates to surgery after primary chemotherapy.
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The present study was funded in part by no-profit organization My Everest.
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In the past 3 years Dr. Michele Reni reports: Grants from: Celgene. Personal Fees from: Celgene, Baxalta, Shire, Eli-lilly, Pfizer, Novocure, Novartis. Non-Financial Support from: Celgene. Steering committee member for: Celgene, Astra-Zeneca, Boston Pharmaceutics. In the past 3 years Dr. Gianpaolo Balzano reports: Personal fees from: Celgene, Roche Diabetes Care GmbH. In the past 3 years Dr. Massimo Falconi has been the member of Advisory Boards for the following companies: Advisory Boards: Celgene, Merck. Consultant: Novartis, Ipsen, AAA. Support for research projects: Novartis, Ipsen, AAA. In the past 3 years Dr. Luca Gianni has been the member of Advisory Boards for the following companies: Advisory Boards: ADC Therapeutics, AstraZeneca, Celgene, Eli Lilly, G1 Therapeutics, Genentech, Genomic Health, Merck Sharp and Dohme, Oncolytics Biotech, Odonate Therapeutics, Onkaido, Roche, Pfizer, Tahio Pharmaceutical, Sandoz, SeaGen, Synthon, Zymeworks. Consultant: CD47, GENENTA, MetIS, Novartis, Odonate Therapeutics, Revolution Medicine, Synaffix, Zymeworks. Support for research projects: Zymeworks, Daiichi SankyoZymeworks, Daiichi Sankyo. Patents: Dr. Gianni is Co-Inventor of ‘European Patent Application N. 12195182.6 and 12196177.5’, titled “PDL-1 expression in anti-HER2 therapy”-Roche. The other authors declare no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of IRCCS San Raffaele Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Reni, M., Peretti, U., Zanon, S. et al. Time to CA19-9 nadir: a clue for defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma. Cancer Chemother Pharmacol 85, 641–650 (2020). https://doi.org/10.1007/s00280-020-04047-7
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DOI: https://doi.org/10.1007/s00280-020-04047-7