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Scoring model with serum albumin and CA19-9 for metastatic pancreatic cancer in second-line treatment: results from the NAPOLEON study

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Abstract

Background

Patients with metastatic pancreatic cancer refractory to first-line chemotherapy (CTx) have few treatment options. It is unclear what kind of patients could be brought about survival benefit by 2nd-line CTx after refractory to gemcitabine + nab-PTX (GnP) or FOLFIRINOX.

Methods

This analysis was conducted as part of a multicenter retrospective study of GnP or FOLFIRINOX in patients with metastatic pancreatic cancer. Excluding censored cases, 156 and 77 patients, respectively, received second-line chemotherapy (CTx) and best supportive care (BSC). Using prognostic factors for post-discontinuation survivals (PDSs) at the first-line determination in multivariate analysis, we developed a scoring system to demonstrate the benefit of second-line CTx.

Results

The second-line CTx group had a median PDS of 5.2 months, whereas the BSC group had a median PDS of 2.7 months (hazard ratio 0.42; 95% confidence interval [CI] 0.31–0.57; p < 0.01). According to the Cox regression model, serum albumin levels below 3.5 g/dL, and CA19-9 levels above 1000 U/mL were independent prognostic factors (p < 0.01). Serum albumin (≥ and < 3.5 g/dL allotted to scores 0 and 1) and CA19-9 (< and ≥ 1000 U/mL allotted to scores 0 and 1) at first-line determination were used to develop the scoring system. The PDSs of patients with scores of 0 and 1 were significantly better than those of the BSC group; however, there was no significant difference between the PDSs of patients with score 2 and the BSC group.

Conclusion

The survival advantage of second-line CTx, was observed in patients with scores of 0 and 1 but not in those with score 2.

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Availability of data and material

All data generated or analyzed in this study are stored in a secured research database. They are not publicly available; however, they are available through the corresponding author upon reasonable request.

Code availability

We used R ver. 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria) for statistical analyses.

References

  1. Carrato A, Falcone A, Ducreux M et al (2015) A systematic review of the burden of pancreatic cancer in europe: real-world impact on survival, quality of life and costs. J Gastrointest Cancer 46:201–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Egawa S, Toma H, Ohigashi H et al (2012) Japan Pancreatic Cancer Registry; 30th year anniversary: Japan Pancreas Society. Pancreas 41:985–992

    Article  PubMed  Google Scholar 

  3. Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703

    Article  Google Scholar 

  4. Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825

    Article  CAS  PubMed  Google Scholar 

  5. Pelzer U, Schwaner I, Stieler J et al (2011) Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 47:1676–1681

    Article  CAS  PubMed  Google Scholar 

  6. Wang-Gillam A, Li CP, Bodoky G et al (2016) 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 387:545–557

    Article  CAS  PubMed  Google Scholar 

  7. Oettle H, Riess H, Stieler JM et al (2014) 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 32:2423–2429

    Article  CAS  PubMed  Google Scholar 

  8. Gill S, Ko YJ, Cripps C et al (2016) PANCREOX: a randomized Phase III Study of Fluorouracil/Leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol 34:3914–3920

    Article  CAS  PubMed  Google Scholar 

  9. Ioka T, Ueno M, Ueno H et al (2019) TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial). Eur J Cancer 106:78–88

    Article  CAS  PubMed  Google Scholar 

  10. Okusaka T, Nakamura M, Yoshida M et al (2020) Committee for revision of clinical guidelines for Pancreatic Cancer of the Japan Pancreas Society. Clinical practice guidelines for pancreatic cancer 2019 from the Japan Pancreas Society: a synopsis. Pancreas 49(3):326–335

  11. Golan T, Hammel P, Reni M et al (2019) Maintenance Olaparib for germline BRCA—mutated metastatic pancreatic cancer. N Engl J Med 381(4):317–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang-Gillam A, Li C-P, Bodoky G et al (2016) Lancet 387(10018):545–557

  13. Hang J, Wu L, Zhu L et al (2018) Prediction of overall survival for metastatic pancreatic cancer: development and validation of a prognostic nomogram with data from open clinical trial and real-world study. Cancer Med 7(7):2974–2984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Goldstein D, Von Hoff DD, Chiorean EG et al (2020) Nomogram for estimating overall survival in patients with metastatic pancreatic cancer. Pancreas 49(6):744–750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. kusaka T, Furuse J, (2020) Recent advances in chemotherapy for pancreatic cancer: evidence from Japan and recommendations in guidelines. J Gastroenterol 55(4):369–382

    Article  Google Scholar 

  16. Arima S, Kawahira M, Shimokawa M et al (2021) 2021) Gemcitabine plus Nab-Paclitaxel versus FOLFIRINOX in locally advanced, unresectable pancreatic cancer: a multicenter observational study (NAPOLEON Study). Pancreas 50:957–964

    Article  CAS  PubMed  Google Scholar 

  17. Otsuka T, Shirakawa T, Shimokawa M et al (2021) A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study. Int J Clin Oncol 26(5):941–950

    Article  CAS  PubMed  Google Scholar 

  18. Wang-Gillam A, Hubner RA, Siveke JT et al (2019) NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors. Eur J Cancer 108:78–87

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  20. Maréchal R, Demols A, Gay F et al (2007) Prognostic factors and prognostic index for chemonaïve and gemcitabine-refractory patients with advanced pancreatic cancer. Oncology 73(1–2):41–51

    Article  PubMed  Google Scholar 

  21. Caparello C, Vivaldi C, Fornaro L et al (2016) Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. Oncology 12(7):901–908

    CAS  Google Scholar 

  22. Haas M, Laubender RP, Stieber P et al (2010) Prognostic relevance of CA 19–9, CEA, CRP, and LDH kinetics in patients treated with palliative second-line therapy for advanced pancreatic cancer. Tumour Biol 31(4):351–357

    Article  CAS  PubMed  Google Scholar 

  23. Shuai-Shuai Xu, Li S, Hua-Xiang Xu et al (2020) World J Gastroenterol 26(8):828–838

    Article  Google Scholar 

  24. Deng QL, Dong S, Wang L et al (2017) Development and validation of a nomogram for predicting survival in patients with advanced pancreatic ductal adenocarcinoma. Sci Rep 7(1):11524

    Article  PubMed  PubMed Central  Google Scholar 

  25. Templeton AJ, McNamara MG, Šeruga B et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 29:106(6)

  26. Glazer ES, Rashid OM, Pimiento JM et al (2016) Increased neutrophil-to-lymphocyte ratio after neoadjuvant therapy is associated with worse survival after resection of borderline resectable pancreatic ductal adenocarcinoma. Surgery 160(5):1288–1293

    Article  PubMed  Google Scholar 

  27. Asari S, Matsumoto I, Toyama H et al (2016) Preoperative independent prognostic factors in patients with borderline resectable pancreatic ductal adenocarcinoma following curative resection: the neutrophil-lymphocyte and platelet-lymphocyte ratios. Surg Today 46(5):583–592

    Article  PubMed  Google Scholar 

  28. Kawai M, Hirono S, Okada K-I et al (2019) Low lymphocyte monocyte ratio after neoadjuvant therapy predicts poor survival after pancreatectomy in patients with borderline resectable pancreatic cancer. Surgery 165(6):1151–1160

    Article  PubMed  Google Scholar 

  29. Hsu CC, Liu KH, Chang PH et al (2020) Development and validation of a prognostic nomogram to predict survival in patients with advanced pancreatic cancer receiving second-line palliative chemotherapy. J Gastroenterol Hepatol 35(10):1694–1703

    Article  CAS  PubMed  Google Scholar 

  30. Sinn M, Dälken L, Striefler JK et al (2016) Second-line treatment in pancreatic cancer patients: who profits?–results from the CONKO Study Group. Pancreas 45(4):601–605

    Article  CAS  PubMed  Google Scholar 

  31. Hirano K, Kawa S, Oguchi H et al (1987) Loss of Lewis antigen expression on erythrocytes in some cancer patients with high serum CA19-9 levels. J Natl Cancer Inst 79(6):1261–1268

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank all of the patients and their families, as well as the researchers from the 14 institutions that participated in the NAPOLEON study. We would also like to acknowledge the cooperation of the Fukuoka Medical Oncology Group–Kyushu Yamaguchi Total Oncology Group (FMOG–KYTOG) and the Saga Study Group for Liver Disease (SASLD). Dr. Y. Kawaguchi of the Saga Medical Centre, Koseikan, and Dr. M. Uenomachi of the Hamanomachi Hospital assisted with data collection and discussion. We would like to thank Enago (https://www.enago.jp) for the English language review.

Funding

This study did not receive any funding.

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan

    Azusa Komori & Satoshi Otsu

  2. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-Machi, Matsuyama, Ehime, 791-0280, Japan

    Azusa Komori

  3. Clinical Research Institute, National Kyushu Cancer Center, 3-1-1 Notame, Minami-Ku, Fukuoka, Fukuoka, 811-1395, Japan

    Mototsugu Shimokawa

  4. Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan

    Mototsugu Shimokawa

  5. Department of Medical Oncology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga, Saga, 840-8571, Japan

    Taiga Otsuka & Norio Ureshino

  6. Department of Internal Medicine, Minato Medical Clinic, 3-11-3 Nagahama, Chuo-Ku, Fukuoka, Fukuoka, 810-0072, Japan

    Taiga Otsuka

  7. Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga, Saga, 840-8571, Japan

    Futa Koga

  8. Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, 2-1-1 Nagamine-Minami, Higashi-Ku, Kumamoto, Kumamoto, 861-8520, Japan

    Yujiro Ueda

  9. Department of Medical Oncology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima, Kagoshima, 890-8760, Japan

    Junichi Nakazawa

  10. Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8520, Japan

    Shiho Arima

  11. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan

    Masaru Fukahori & Yoshinobu Okabe

  12. Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan

    Masaru Fukahori

  13. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1 Kishinoura, Yahatanishi-Ku, Kitakyushu, Fukuoka, 806-8501, Japan

    Akitaka Makiyama

  14. Cancer Center, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan

    Akitaka Makiyama

  15. Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-Cho, Satsumasendai, Kagoshima, 895-0074, Japan

    Hiroki Taguchi

  16. Department of Gastroenterology, Kagoshima City Hospital, 37-1 Uearata-cho, Kagoshima, Kagoshima, 890-8760, Japan

    Hiroki Taguchi

  17. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan

    Takuya Honda

  18. Department of Internal Medicine, Imari Arita Kyoritsu Hospital, 860 Ninose-Ko, Arita-Cho, Nishi-Matsuura-Gun, Saga, 849-4193, Japan

    Taro Shibuki & Toshihiko Mizuta

  19. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Taro Shibuki

  20. Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-Cho, Sasebo, Nagasaki, 857-8575, Japan

    Kenta Nio & Kenji Mitsugi

  21. Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-Ku, Fukuoka, Fukuoka, 810-8539, Japan

    Kenta Nio & Kenji Mitsugi

  22. Department of Internal Medicine, Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan

    Yasushi Ide

  23. Department of Internal Medicine, National Hospital Organization Saga Hospital, 1-20-1 Hinode, Saga, Saga, 849-8577, Japan

    Yasushi Ide

  24. Department of Medical Oncology, Kimitsu Chuo Hospital, 1010 Sakurai, Kisarazu, Chiba, 292-8535, Japan

    Norio Ureshino

  25. Department of Internal Medicine, Fujikawa Hospital, 1-2-6 Matsubara, Saga, Saga, 840-0831, Japan

    Toshihiko Mizuta

  26. Department of Medical Oncology, Fukuoka Wajiro Hospital, 2-2-75 Wajirogaoka, Higashi-Ku, Fukuoka, Fukuoka, 811-0213, Japan

    Tsuyoshi Shirakawa

  27. Department of Internal Medicine, Karatsu Higashi-Matsuura Medical Association Center, 2566-11 Chiyoda-Machi, Karatsu, Saga, 847-0041, Japan

    Tsuyoshi Shirakawa

Authors
  1. Azusa Komori
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  2. Satoshi Otsu
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  3. Mototsugu Shimokawa
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  4. Taiga Otsuka
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  5. Futa Koga
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  6. Yujiro Ueda
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  7. Junichi Nakazawa
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  8. Shiho Arima
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  9. Masaru Fukahori
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  10. Yoshinobu Okabe
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  11. Akitaka Makiyama
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  12. Hiroki Taguchi
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  13. Takuya Honda
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  14. Taro Shibuki
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  15. Kenta Nio
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  16. Yasushi Ide
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  17. Norio Ureshino
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  18. Toshihiko Mizuta
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  19. Tsuyoshi Shirakawa
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  20. Kenji Mitsugi
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Contributions

Study concepts: AK, SO, TO, NU, TM, TS, KM. Study design: AK, SO, MS, TO, MF, AM, NU, TM, TS, KM. Data acquisition: AK, SO, TO, FK, YU, JN, SA, MF, YO, AM, HT, TH, TS, KN, YI, NU, TM, TS, KM. Quality control of data and algorithms: AK, SO, MS, TO, TS, KM. Data analysis and interpretation: AK, SO, MS, TO, TM, TS, KM. Statistical analysis: AK, SO, MS, TO, TS, KM. Manuscript preparation: AK. Manuscript editing: TO, TM, TS, KM. Manuscript review: All authors.

Corresponding author

Correspondence to Tsuyoshi Shirakawa.

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Conflict of interest

T.O. received grant from Chugai; T.S. received consulting fees from Taiho Pharmaceutical, Chugai, and Takeda; M.S. received personal fee from Sysmex Corporation; Y.K. received personal fee from Taiho Pharmaceutical; S.A. received personal fees from Taiho Pharmaceutical, Novartis Pharma, Chugai, Bristol-Myers Squibb, Daiichi-Sankyo, and AstraZeneca; A.M. received personal fees from Eli Lilly, Chugai, and Takeda. The remaining authors have no competing interests or financial disclosures to declare.

Ethics approval

This study was approved by the institutional review board or ethics committee of each participating institution prior to the study and conducted according to the Declaration of Helsinki.

Consent to participate

The requirement for consent to participate was waived because of the retrospective design of this study.

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The requirement for consent for publication was waived because of the retrospective design of this study.

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Komori, A., Otsu, S., Shimokawa, M. et al. Scoring model with serum albumin and CA19-9 for metastatic pancreatic cancer in second-line treatment: results from the NAPOLEON study. Int J Clin Oncol 28, 1073–1081 (2023). https://doi.org/10.1007/s10147-023-02354-6

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  • DOI: https://doi.org/10.1007/s10147-023-02354-6

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