First- and Second-Line Palliative Systemic Treatment Outcomes in a Real-World Metastatic Pancreatic Cancer Cohort

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  • 1 Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam;
  • | 2 Netherlands Cancer Registry, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht;
  • | 3 Department of Internal Medicine, Division of Medical Oncology, GROW–School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht;
  • | 4 Isala Oncology Center, Isala, Zwolle;
  • | 5 Department of Medical Oncology, Erasmus Medical Center;
  • | 6 Department of Medical Oncology, Catharina Hospital, Eindhoven;
  • | 7 Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht; and
  • | 8 Amsterdam UMC, University of Amsterdam, Department of Surgery, Cancer Center Amsterdam, Amsterdam, the Netherlands.

Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor survival rate, which can be improved by systemic treatment. Consensus on the most optimal first- and second-line palliative systemic treatment is lacking. The aim of this study was to describe the use of first- and second-line systemic treatment, overall survival (OS), and time to failure (TTF) of first- and second-line treatment in metastatic PDAC in a real-world setting. Patients and Methods: Patients with synchronous metastatic PDAC diagnosed between 2015 and 2018 who received systemic treatment were selected from the nationwide Netherlands Cancer Registry. OS and TTF were evaluated using Kaplan-Meier curves with log-rank test and multivariable Cox proportional hazard analyses. Results: The majority of 1,586 included patients received FOLFIRINOX (65%), followed by gemcitabine (18%), and gemcitabine + nab-paclitaxel (13%) in the first line. Median OS for first-line FOLFIRINOX, gemcitabine + nab-paclitaxel, and gemcitabine monotherapy was 6.6, 4.7, and 2.9 months, respectively. Compared to FOLFIRINOX, gemcitabine + nab-paclitaxel showed significantly inferior OS after adjustment for confounders (hazard ratio [HR], 1.20; 95% CI, 1.02–1.41), and gemcitabine monotherapy was independently associated with a shorter OS and TTF (HR, 1.98; 95% CI, 1.71–2.30 and HR, 2.31; 95% CI, 1.88–2.83, respectively). Of the 121 patients who received second-line systemic treatment, 33% received gemcitabine + nab-paclitaxel, followed by gemcitabine (31%) and FOLFIRINOX (10%). Conclusions: Based on population-based data in patients with metastatic PDAC, treatment predominantly consists of FOLFIRINOX in the first line and gemcitabine with or without nab-paclitaxel in the second line. FOLFIRINOX in the first line shows superior OS compared with gemcitabine with or without nab-paclitaxel.

Submitted October 29, 2020; final revision received January 29, 2021; accepted for publication February 17, 2021. Published online August 27, 2021.

Author contributions: Study concept: All authors. Data curation: Pijnappel, van der Geest. Formal analysis: Pijnappel. Investigation: van Laarhoven, Wilmink. Methodology: Pijnappel, Dijksterhuis. Project administration: Pijnappel. Resources: Pijnappel. Supervision: van Laarhoven, Wilmink. Validation: van Laarhoven, Wilmink. Visualization: Pijnappel, van Laarhoven, Wilmink. Writing – original draft: Pijnappel, Dijksterhuis, van der Geest, van Laarhoven, Wilmink. Writing – review and editing: All authors.

Disclosures: Dr. de Vos-Geelen has disclosed receiving nonfinancial and institutional research support from Servier, and serving as an advisory board member for Amgen, AstraZeneca, MSD, Pierre Fabre, and Servier. Dr. de Groot has disclosed serving as an advisory board member for BMS and MSD. Dr. Hohammad has disclosed serving as a scientific advisor for Servier, Merck, Eli Lilly, and BMS, and receiving grant/research support from Servier. Dr. van Laarhoven has disclosed serving as a consultant for BMS, Celgene, Lilly, MSD/Merck, Nordic Pharma, and Servier; receiving unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, Philips, Roche, and Servier; and serving as a consultant for BMS, Lilly, MSD, Nordic Pharma, and Servier. Dr. Wilmink has disclosed serving as a consultant for Shire, Servier, and Celgene; receiving grant support from Servier, Halozyne, Novartis, Celgene, AstraZeneca, Pfizer, Roche, Amgen, and MSD/Merck; and serving as an advisory board member for Servier, Celgene, MSD/Merck, and Novartis. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Johanna W. Wilmink, MD, PhD, Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Meibergdreef 9, D3-221.1, 1105 AZ Amsterdam, The Netherlands. Email: j.w.wilmink@amsterdamumc.nl

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    • Supplemental Materials (PDF 574 KB)
  • 1.

    Gränsmark E, Bågenholm Bylin N, Blomstrand H, et al. Real world evidence on second-line palliative chemotherapy in advanced pancreatic cancer. Front Oncol 2020;10:1176.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Paluri RK, Kasi A, Young C, et al. Second-line treatment for metastatic pancreatic cancer. Clin Adv Hematol Oncol 2020;18:106115.

  • 3.

    Taieb J, Pointet AL, Van Laethem JL, et al. What treatment in 2017 for inoperable pancreatic cancers? Ann Oncol 2017;28:14731483.

  • 4.

    Gilabert M, Chanez B, Rho YS, et al. Evaluation of gemcitabine efficacy after the FOLFIRINOX regimen in patients with advanced pancreatic adenocarcinoma. Medicine (Baltimore) 2017;96:e6544.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Ellenrieder V, König A, Seufferlein T. Current standard and future perspectives in first- and second-line treatment of metastatic pancreatic adenocarcinoma. Digestion 2016;94:4449.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Aprile G, Negri FV, Giuliani F, et al. Second-line chemotherapy for advanced pancreatic cancer: which is the best option? Crit Rev Oncol Hematol 2017;115:112.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Vienot A, Beinse G, Louvet C, et al. Overall survival prediction and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma. J Natl Cancer Inst 2017;109:djx037.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Arslan C, Yalcin S. Current and future systemic treatment options in metastatic pancreatic cancer. J Gastrointest Oncol 2014;5:280295.

  • 9.

    Berlin JD, Catalano P, Thomas JP, et al. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 2002;20:32703275.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009;27:55135518.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Hidalgo M. Pancreatic cancer. N Engl J Med 2010;362:16051617.

  • 12.

    Heinemann V, Vehling-Kaiser U, Waldschmidt D, et al. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104). Gut 2013;62:751759.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:18171825.

  • 14.

    Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:16911703.

  • 15.

    Latenstein AEJ, Mackay TM, Creemers GJ, et al. Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis. Acta Oncol 2020;59:705712.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Chin V, Nagrial A, Sjoquist K, et al. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Rev 2018;3:CD011044.

  • 17.

    Veereman G, Mohammad NH, Van Leeuwen M, et al. Management of pancreatic cancer–p0art 4: recurrent and metastatic cancer. Good Clinical Practice (GCP) Brussels: Belgian Health Care Knowledge Centre (KCE). KCE Reports 286. D/2017/10.273/32.

    • Search Google Scholar
    • Export Citation
  • 18.

    Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet 2016;387:545557.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Templeton AJ, Booth CM, Tannock IF. Informing patients about expected outcomes: the efficacy-effectiveness gap. J Clin Oncol 2020;38:16511654.

  • 20.

    von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med 2007;4:e296.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Sarkar RR, Matsuno R, Murphy JD. Pancreatic cancer: survival in clinical trials versus the real world [abstract]. J Clin Oncol 2016;34(Suppl):Abstract 216.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Wang Y, Camateros P, Cheung WY. A real-world comparison of FOLFIRINOX, gemcitabine plus nab-paclitaxel, and gemcitabine in advanced pancreatic cancers. J Gastrointest Cancer 2019;50:6268.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Kieler M, Unseld M, Bianconi D, et al. Impact of new chemotherapy regimens on the treatment landscape and survival of locally advanced and metastatic pancreatic cancer patients. J Clin Med 2020;9:648.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Papneja N, Zaidi A, Chalchal H, et al. Comparisons of outcomes of real-world patients with advanced pancreatic cancer treated with FOLFIRINOX versus gemcitabine and nab-paclitaxel: a population-based cohort study. Pancreas 2019;48:920926.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Chan KKW, Guo H, Cheng S, et al. Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: a population-based propensity score-weighted analysis. Cancer Med 2020;9:160169.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    van der Geest LGM, Haj Mohammad N, Besselink MGH, et al. Nationwide trends in chemotherapy use and survival of elderly patients with metastatic pancreatic cancer. Cancer Med 2017;6:28402849.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Lambert A, Gavoille C, Conroy T. Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. Therap Adv Gastroenterol 2017;10:631645.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Ko AH. FOLFIRINOX: a small step or a great leap forward? J Clin Oncol 2011;29:37273729.

  • 29.

    Peixoto RD, Ho M, Renouf DJ, et al. Eligibility of metastatic pancreatic cancer patients for first-line palliative intent nab-paclitaxel plus gemcitabine versus FOLFIRINOX. Am J Clin Oncol 2017;40:507511.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Beesley VL, Wockner LF, O’Rourke P, et al. Risk factors for current and future unmet supportive care needs of people with pancreatic cancer. A longitudinal study. Support Care Cancer 2016;24:35893599.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Védie AL, Neuzillet C. Pancreatic cancer: best supportive care. Presse Med 2019;48:e175e185.

  • 32.

    Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol 2014;32:24232429.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Earle CC, Landrum MB, Souza JM, et al. Aggressiveness of cancer care near the end of life: is it a quality-of-care issue? J Clin Oncol 2008;26:38603866.

  • 34.

    Schnipper LE, Smith TJ, Raghavan D, et al. American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology. J Clin Oncol 2012;30:17151724.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Fest J, Ruiter R, van Rooij FJ, et al. Underestimation of pancreatic cancer in the national cancer registry: reconsidering the incidence and survival rates. Eur J Cancer 2017;72:186191.

    • Crossref
    • Search Google Scholar
    • Export Citation
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