Cancer Chemotherapy and Pharmacology

, Volume 79, Issue 3, pp 595–602 | Cite as

Positive relationship between subsequent chemotherapy and overall survival in pancreatic cancer: meta-analysis of postprogression survival for first-line chemotherapy

  • Akiyoshi Kasuga
  • Yasuo Hamamoto
  • Ayano Takeuchi
  • Kenta Kawasaki
  • Takeshi Suzuki
  • Kenro Hirata
  • Yasutaka Sukawa
  • Hiromasa Takaishi
  • Takanori Kanai
Original Article



To gain a better understanding of the impact of postprogression survival (PPS) and post-trial anticancer therapy on overall survival (OS) in first-line pancreatic cancer patients.


A literature search identified 54 randomized trials, focusing on gemcitabine monotherapy to eliminate effects of heterogeneity of first-line regimens. We evaluated the relation between OS and either progression-free survival (PFS) or PPS. We also examined whether any association might be affected by the year of completion of trial enrollment.


For all 54 trials, PPS was strongly associated with OS (r = 0.844), whereas PFS was moderately associated with OS (r = 0.623). Average OS and PPS were significantly longer in recent trials than in older trials, (7.29 versus 6.15 months, p < 0.001) and (3.64 versus 2.86 months, p < 0.001), respectively. The correlation between OS and PPS in recent trials was much stronger than that in older trials (r = 0.846 versus 0.729). The relation between OS and PFS in recent and older trials did not differ (r = 0.595 versus 0.563). The percentage of patients with post-trial treatment was significantly higher in recent trials than in older trials (52.7 versus 39.7%, p < 0.001). The rate of post-trial anticancer therapy was significantly associated with OS (r = 0.910).


We found an increase in median PPS in accordance with an increase in median OS in recent trials compared with older trials and that rate of post-trial anticancer therapy was strongly associated with median OS. It is important that researchers be aware of these findings in designing clinical trials of first-line chemotherapy for pancreatic cancer patients.


Pancreatic cancer Meta-analysis Randomized controlled trial Gemcitabine Chemotherapy Postprogression survival 



Pancreatic cancer




Overall survival


Progression-free survival


Postprogression survival


Time to progression


Standard error


Compliance with ethical standards

Conflict of interest

None to declare.

Supplementary material

280_2017_3263_MOESM1_ESM.docx (110 kb)
Supplementary material 1 (DOCX 109 KB)


  1. 1.
    Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E (2013) European cancer mortality predictions for the year 2013. Ann Oncol Off J Eur Soc Med Oncol/ESMO 24(3):792–800. doi: 10.1093/annonc/mdt010 CrossRefGoogle Scholar
  2. 2.
    Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol Off J Am Soc Clin Oncol 15(6):2403–2413CrossRefGoogle Scholar
  3. 3.
    Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol Off J Am Soc Clin Oncol 25(15):1960–1966. doi: 10.1200/jco.2006.07.9525 CrossRefGoogle Scholar
  4. 4.
    Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825. doi: 10.1056/NEJMoa1011923 CrossRefPubMedGoogle Scholar
  5. 5.
    Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703. doi: 10.1056/NEJMoa1304369 CrossRefGoogle Scholar
  6. 6.
    Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, Gorner M, Molle M, Greten TF, Lakner V, Bischoff S, Sinn M, Dorken B, Pelzer U (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 Off J Am Soc Clin Oncol 32(23):2423–2429. doi: 10.1200/jco.2013.53.6995 CrossRefGoogle Scholar
  7. 7.
    Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M (2013) Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol Off J Am Soc Clin Oncol 31(13):1640–1648. doi: 10.1200/jco.2012.43.3680 CrossRefGoogle Scholar
  8. 8.
    Saad ED, Katz A, Buyse M (2010) Overall survival and post-progression survival in advanced breast cancer: a review of recent randomized clinical trials. J Clin Oncol Off J Am Soc Clin Oncol 28(11):1958–1962. doi: 10.1200/jco.2009.25.5414 CrossRefGoogle Scholar
  9. 9.
    Petrelli F, Barni S (2013) Correlation of progression-free and post-progression survival with overall survival in advanced colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol/ESMO 24(1):186–192. doi: 10.1093/annonc/mds289 CrossRefGoogle Scholar
  10. 10.
    Hayashi H, Okamoto I, Morita S, Taguri M, Nakagawa K (2012) Postprogression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer. Ann Oncol Off J Eur Soc Med Oncol/ESMO 23(6):1537–1541. doi: 10.1093/annonc/mdr487 CrossRefGoogle Scholar
  11. 11.
    Kawakami H, Okamoto I, Hayashi H, Taguri M, Morita S, Nakagawa K (2013) Postprogression survival for first-line chemotherapy in patients with advanced gastric cancer. Eur J Cancer (Oxford, England: 1990) 49 (14):3003–3009. doi: 10.1016/j.ejca.2013.05.022 CrossRefGoogle Scholar
  12. 12.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Controlled clinical trials 7(3):177–188Google Scholar
  13. 13.
    Hotta K, Kiura K, Fujiwara Y, Takigawa N, Hisamoto A, Ichihara E, Tabata M, Tanimoto M (2011) Role of survival post-progression in phase III trials of systemic chemotherapy in advanced non-small-cell lung cancer: a systematic review. PLoS One 6(11):e26646. doi: 10.1371/journal.pone.0026646 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Nakai Y, Isayama H, Sasaki T, Sasahira N, Tsujino T, Toda N, Kogure H, Matsubara S, Ito Y, Togawa O, Arizumi T, Hirano K, Tada M, Omata M, Koike K (2012) A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. Br J Cancer 106(12):1934–1939. doi: 10.1038/bjc.2012.183 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ozaka M, Matsumura Y, Ishii H, Omuro Y, Itoi T, Mouri H, Hanada K, Kimura Y, Maetani I, Okabe Y, Tani M, Ikeda T, Hijioka S, Watanabe R, Ohoka S, Hirose Y, Suyama M, Egawa N, Sofuni A, Ikari T, Nakajima T (2012) Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study). Cancer Chemother Pharmacol 69(5):1197–1204. doi: 10.1007/s00280-012-1822-1 CrossRefPubMedGoogle Scholar
  16. 16.
    Sudo K, Ishihara T, Hirata N, Ozawa F, Ohshima T, Azemoto R, Shimura K, Nihei T, Nishino T, Nakagawa A, Nakamura K, Hara T, Tada M, Mikata R, Tawada K, Yokosuka O, Nakaji S, Yamaguchi T (2014) Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer. Cancer Chemother Pharmacol 73(2):389–396. doi: 10.1007/s00280-013-2368-6 CrossRefPubMedGoogle Scholar
  17. 17.
    Poruk KE, Firpo MA, Adler DG, Mulvihill SJ (2013) Screening for pancreatic cancer: why, how, and who? Ann Surg 257(1):17–26. doi: 10.1097/SLA.0b013e31825ffbfb CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Neal RD (2009) Do diagnostic delays in cancer matter? Br J Cancer 101(Suppl 2):S9–S12. doi: 10.1038/sj.bjc.6605384 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Richards MA (2009) The national awareness and early diagnosis initiative in England: assembling the evidence. Br J Cancer 101(Suppl 2):S1–S4. doi: 10.1038/sj.bjc.6605382 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Olesen F, Hansen RP, Vedsted P (2009) Delay in diagnosis: the experience in Denmark. Br J Cancer 101(Suppl 2):S5–S8. doi: 10.1038/sj.bjc.6605383 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Neal RD, Din NU, Hamilton W, Ukoumunne OC, Carter B, Stapley S, Rubin G (2014) Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database. Br J Cancer 110(3):584–592. doi: 10.1038/bjc.2013.791 CrossRefPubMedGoogle Scholar
  22. 22.
    Broglio KR, Berry DA (2009) Detecting an overall survival benefit that is derived from progression-free survival. J Natl Cancer Inst 101(23):1642–1649. doi: 10.1093/jnci/djp369 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Akiyoshi Kasuga
    • 1
  • Yasuo Hamamoto
    • 1
  • Ayano Takeuchi
    • 2
  • Kenta Kawasaki
    • 1
  • Takeshi Suzuki
    • 1
  • Kenro Hirata
    • 1
  • Yasutaka Sukawa
    • 1
  • Hiromasa Takaishi
    • 1
  • Takanori Kanai
    • 1
  1. 1.Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of MedicineKeio UniversityTokyoJapan
  2. 2.Department of Preventive Medicine and Public Health, School of MedicineKeio UniversityTokyoJapan

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