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Magnitude of advantage in tumor response contributes to a better correlation between treatment effects on overall survival and progression-free survival: a literature-based meta-analysis of clinical trials in patients with metastatic colorectal cancer

  • Yosuke YoshidaEmail author
  • Masayuki Kaneko
  • Mamoru Narukawa
Original Article
  • 21 Downloads

Abstract

Background

Although it is suggested that the endpoints originated from the concept of tumor shrinkage dynamics, such as early tumor shrinkage and depth of response, are strongly associated with overall survival (OS) in patients with metastatic colorectal cancer (mCRC), they are yet to be validated as a single surrogate endpoint of OS by themselves. This study aimed to investigate the impact of advantage in tumor response on the correlation between treatment effects on progression-free survival (PFS) and OS in mCRC patients.

Methods

Based on an electronic search, we identified randomized controlled trials of first-line therapy for mCRC. The impact of advantage in objective response rate (ORR) on the correlation between treatment effects on PFS and OS was evaluated based on Spearman correlation coefficients (rs).

Results

Forty-seven trials with a total of 24,018 patients were identified. The hazard ratio for PFS showed a relatively higher correlation with that for OS (rs = 0.63) when the trials were limited to those that demonstrated a larger difference in ORR, compared to the case for trials that demonstrated a smaller difference (rs = 0.32). This tendency was also observed in the subgroup analysis stratified by the types of treatment agents (targeted or non-targeted).

Conclusions

The magnitude of advantage in tumor response was suggested to contribute to a better prediction of OS benefit based on PFS in patients with mCRC. The accuracy of OS estimation in mCRC is expected to be improved by considering the degree of tumor shrinkage in conjunction with PFS.

Keywords

Colorectal cancer Survival Surrogate endpoint Meta-analysis 

Notes

Acknowledgements

We would like to thank Kae Nakashima, Ph.D., for her support in English editing.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by YY and MK. The first draft of the manuscript was written by YY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All authors have no conflicts of interest that are directly relevant to this research. Yosuke Yoshida is an employee of MSD K.K., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Supplementary material

10147_2020_1619_MOESM1_ESM.docx (40 kb)
Supplementary file1 (DOCX 39 kb)

References

  1. 1.
    Food and Drug Administration (2018) Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. US department of health and human services. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trial-endpoints-approval-cancer-drugs-and-biologics
  2. 2.
    Serugal B, Ocana A, Amir E et al (2015) Failures in phase III: causes and consequences. Clin Cancer Res 21(20):4552–4560.  https://doi.org/10.1158/1078-0432.CCR-15-0124 CrossRefGoogle Scholar
  3. 3.
    Douaiher J, Ravipati A, Chowdhury S (2017) Colorectal cancer–global burden, trends, and geographical variations. J Surg Oncol 115:619–630.  https://doi.org/10.1002/jso.24578 CrossRefPubMedGoogle Scholar
  4. 4.
    Schwartzberg LS, Rivera F, Karthaus M et al (2014) PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol 32(21):2240–2247.  https://doi.org/10.1200/JCO.2013.53.2473 CrossRefPubMedGoogle Scholar
  5. 5.
    Stintzing S, Modest DP, Rossius L et al (2016) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol 17:1426–1434.  https://doi.org/10.1016/S1470-2045(16)30269-8 CrossRefPubMedGoogle Scholar
  6. 6.
    Haslam A, Hey SP, Gill J et al (2019) A systematic review of trial-level meta-analyses measuring the strength of association between surrogate end-points and overall survival in oncology. Eur J Cancer 106:196–211.  https://doi.org/10.1016/j.ejca.2018.11.012 CrossRefPubMedGoogle Scholar
  7. 7.
    Piessevaux H, Buyse M, Schlichting M et al (2013) Use of early tumor shrinkage to predict long-term outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol 31:3764–3775.  https://doi.org/10.1200/JCO.2012.42.8532 CrossRefPubMedGoogle Scholar
  8. 8.
    Mansmann UR, Sartorius U, Laubender RP et al (2013) Quantitative analysis of the impact of deepness of response on post-progression survival time following first-line treatment in patients with mCRC. J Clin Oncol 31(15). https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.3630
  9. 9.
    Cremolini C, Loupakis F, Antoniotti C et al (2015) Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol 26:1188–1194.  https://doi.org/10.1093/annonc/mdv112 CrossRefPubMedGoogle Scholar
  10. 10.
    Douillard JY, Siena S, Peeters M et al (2015) Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer. Eur J Cancer 51:1231–1242.  https://doi.org/10.1016/j.ejca.2015.03.026 CrossRefPubMedGoogle Scholar
  11. 11.
    Tsuji A, Sunakawa Y, Ichikawa W et al (2016) Early tumor shrinkage and depth of response as predictors of favorable treatment outcomes in patients with metastatic colorectal cancer treated with FOLFOX Plus Cetuximab (JACCRO CC-05). Targ Oncol 11:799–806.  https://doi.org/10.1007/s11523-016-0445-6 CrossRefGoogle Scholar
  12. 12.
    Petrelli F, Pietrantonio F, Cremolini C et al (2015) Early tumour shrinkage as a prognostic factor and surrogate end-point in colorectal cancer: A systematic review and pooled-analysis. Eur J Cancer 51(7):800–807.  https://doi.org/10.1016/j.ejca.2015.02.011 CrossRefPubMedGoogle Scholar
  13. 13.
    Nakayama G, Fujii T, Murotani K et al (2016) Modified two-dimensional response as surrogate marker of overall survival in patients with metastatic colorectal cancer. Cancer Sci 107(10):1492–1498.  https://doi.org/10.1111/cas.13023 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hutton B, Salanti G, Caldwell DM et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162(11):777–784.  https://doi.org/10.7326/M14-2385 CrossRefGoogle Scholar
  15. 15.
    Giessen C, Laubender RP, Ankerst DP et al (2013) Progression-free survival as a surrogate endpoint for median overall survival in metastatic colorectal cancer: literature-based analysis from 50 randomized first-line trials. Clin Cancer Res 19(1):225–235.  https://doi.org/10.1158/1078-0432.CCR-12-1515 CrossRefPubMedGoogle Scholar
  16. 16.
    Broglio KR, Berry DA (2009) Detecting an overall survival benefit that is derived from progression-free survival. J Natl Cancer Inst 101:1642–1649.  https://doi.org/10.1093/jnci/djp369 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Morita S, Sakamaki K, Yin G (2015) Detecting overall survival benefit derived from survival postprogression rather than progression-free survival. J Natl Cancer Inst 107:djv133.  https://doi.org/10.1093/jnci/djv133 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Burzykowski T, Buyse M, Piccart-Gebhart MJ et al (2008) Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer. J Clin Oncol 26:1987–1992.  https://doi.org/10.1200/JCO.2007.10.8407 CrossRefPubMedGoogle Scholar
  19. 19.
    Tang PA, Bentzen SM, Chen EX et al (2007) Surrogate end points for median overall survival in metastatic colorectal cancer: literature-based analysis from 39 randomized controlled trials of first-line chemotherapy. J Clin Oncol 25(29):4562–4568.  https://doi.org/10.1200/JCO.2006.08.1935 CrossRefPubMedGoogle Scholar
  20. 20.
    Aparicio T, Lavau-Denes S, Phelip JM et al (2016) Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02). Ann Oncol 27:121–127.  https://doi.org/10.1093/annonc/mdv491 CrossRefPubMedGoogle Scholar
  21. 21.
    Passardi A, Nanni O, Tassinari D et al (2015) Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial. Ann Oncol 26:1201–1207.  https://doi.org/10.1093/annonc/mdv130 CrossRefPubMedGoogle Scholar
  22. 22.
    Brodowicz T, Ciuleanu TE, Radosavljevic D et al (2013) FOLFOX4 plus cetuximab administered weekly or every second week in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer: a randomized phase II CECOG study. Ann Oncol 24:1769–1777.  https://doi.org/10.1093/annonc/mdt116 CrossRefPubMedGoogle Scholar
  23. 23.
    Labianca R, Sobrero A, Isa L et al (2011) Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised ‘GISCAD’ trial. Ann Oncol 22:1236–1242.  https://doi.org/10.1093/annonc/mdq580 CrossRefPubMedGoogle Scholar
  24. 24.
    Bokemeyer C, Bondarenko I, Hartmann JT et al (2011) Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 22:1535–1546.  https://doi.org/10.1093/annonc/mdq632 CrossRefPubMedGoogle Scholar
  25. 25.
    Glimelius B, Sørbye H, Balteskard L et al (2008) A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer. Ann Oncol 19(5):909–914.  https://doi.org/10.1093/annonc/mdm588 CrossRefPubMedGoogle Scholar
  26. 26.
    Punt CJ, Keizer HJ, Douma J et al (2002) Trimetrexate as biochemical modulator of 5-fluorouracil/leucovorin in advanced colorectal cancer: final results of a randomised European study. Ann Oncol 13(1):81–86.  https://doi.org/10.1093/annonc/mdf045 CrossRefPubMedGoogle Scholar
  27. 27.
    Blanke CD, Shultz J, Cox J et al (2002) A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer. Ann Oncol 13(1):87–91.  https://doi.org/10.1093/annonc/mdf043 CrossRefPubMedGoogle Scholar
  28. 28.
    Kalofonos HP, Papakostas P, Makatsoris T et al (2010) Irinotecan/fluorouracil/leucovorin or the same regimen followed by oxaliplatin/fluorouracil/leucovorin in metastatic colorectal cancer. Anticancer Res 30(10): 4325–4333. https://ar.iiarjournals.org/content/30/10/4325.long
  29. 29.
    Souglakos J, Ziras N, Kakolyris S et al (2012) Randomised phase trial of CAPIRI capecitabine, irinotecan plus bevacizumab vs FOLFIRI folinic acid, 5fluorouracil, irinotecan plus bevacizumab as first-line treatment of patients with unresectablemetastatic colorectal cancer mCRC. Br J Cancer 106(3):453–459.  https://doi.org/10.1038/bjc.2011.594 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Yamazaki K, Kuwano H, Ojima H et al (2015) A randomized phase II study of combination therapy with S-1, oral leucovorin, and oxaliplatin (SOL) and mFOLFOX6 in patients with previously untreated metastatic colorectal cancer. Cancer Chemother Pharmacol 75(3):569–577.  https://doi.org/10.1007/s00280-015-2676-0 CrossRefPubMedGoogle Scholar
  31. 31.
    Guan ZZ, Xu JM, Luo RC et al (2011) Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial. Chin J Cancer 30(10):682–689.  https://doi.org/10.5732/cjc.011.10188 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Cao B, Li ST, Li Z et al (2011) Yiqi zhuyu decoction combined with FOLFOX-4 as first-line therapy in metastatic colorectal cancer. Chin J Integr Med 17(8):593–599.  https://doi.org/10.1007/s11655-011-0822-z CrossRefPubMedGoogle Scholar
  33. 33.
    Tabernero J, Garcia-Carbonero R, Cassidy J et al (2013) Sorafenib in combination with oxaliplatin, leucovorin, and fluorouracil (modified FOLFOX6) as first-line treatment of metastatic colorectal cancer: the RESPECT trial. Clin Cancer Res 19(9):2541–2550.  https://doi.org/10.1158/1078-0432.CCR-13-0107 CrossRefPubMedGoogle Scholar
  34. 34.
    Douillard JY, Zemelka T, Fountzilas G et al (2014) FOLFOX4 with cetuximab vs UFOX with cetuximab as firstline therapy in metastatic colorectal cancer The randomized phase FUTURE study. Clin Colorectal Cancer 13(1):14–26.e1.  https://doi.org/10.1016/j.clcc.2013.11.009 CrossRefPubMedGoogle Scholar
  35. 35.
    Gravalos C, Salut A, García-Girón C et al (2012) A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer. Clin Transl Oncol 14(8):606–612.  https://doi.org/10.1007/s12094-012-0843-x CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ducreux M, Bennouna J, Hebbar M et al (2011) Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer. Int J Cancer 128(3):682–690.  https://doi.org/10.1002/ijc.25369 CrossRefPubMedGoogle Scholar
  37. 37.
    Comella P, Massidda B, Filippelli G et al (2009) Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401. J Cancer Res Clin Oncol 135(2):217–226.  https://doi.org/10.1007/s00432-008-0454-7 CrossRefPubMedGoogle Scholar
  38. 38.
    Hoff PM, Hochhaus A, Pestalozzi BC et al (2012) Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II). J Clin Oncol 30(29):3596–3603.  https://doi.org/10.1200/JCO.2012.42.6031 CrossRefPubMedGoogle Scholar
  39. 39.
    Schmoll HJ, Cunningham D, Sobrero A et al (2012) Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III). J Clin Oncol 30(29):3588–3595.  https://doi.org/10.1200/JCO.2012.42.5355 CrossRefPubMedGoogle Scholar
  40. 40.
    Tveit KM, Guren T, Glimelius B et al (2012) Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 30(15):1755–1762.  https://doi.org/10.1200/JCO.2011.38.0915 CrossRefPubMedGoogle Scholar
  41. 41.
    Douillard JY, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28(31):4697–4705.  https://doi.org/10.1200/JCO.2009.27.4860 CrossRefPubMedGoogle Scholar
  42. 42.
    Tebbutt NC, Wilson K, Gebski VJ et al (2010) Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 28(19):3191–3198.  https://doi.org/10.1200/JCO.2009.27.7723 CrossRefPubMedGoogle Scholar
  43. 43.
    Saltz LB, Clarke S, Díaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26(12):2013–2019.  https://doi.org/10.1200/JCO.2007.14.9930 CrossRefPubMedGoogle Scholar
  44. 44.
    Porschen R, Arkenau HT, Kubicka S et al (2007) Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 25(27):4217–4223.  https://doi.org/10.1200/JCO.2006.09.2684 CrossRefPubMedGoogle Scholar
  45. 45.
    Falcone A, Ricci S, Brunetti I et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25(13):1670–1676.  https://doi.org/10.1200/JCO.2006.09.0928 CrossRefPubMedGoogle Scholar
  46. 46.
    Kabbinavar FF, Schulz J, McCleod M et al (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23(16):3697–3705.  https://doi.org/10.1200/JCO.2005.05.112 CrossRefPubMedGoogle Scholar
  47. 47.
    Köhne CH, van Cutsem E, Wils J et al (2005) Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: european organisation for research and treatment of cancer gastrointestinal group study 40986. J Clin Oncol 23(22):4856–4865.  https://doi.org/10.1200/JCO.2005.05.546 CrossRefPubMedGoogle Scholar
  48. 48.
    Schilsky RL, Levin J, West WH et al (2002) Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer. J Clin Oncol 20(6):1519–1526.  https://doi.org/10.1200/JCO.2002.20.6.1519 CrossRefPubMedGoogle Scholar
  49. 49.
    Seymour MT, Slevin ML, Kerr DJ et al (1996) Randomized trial assessing the addition of interferon alpha-2a to fluorouracil and leucovorin in advanced colorectal cancer. Colorectal Cancer Working Party of the United Kingdom Medical Research Council. J Clin Oncol 14(8):2280–2288.  https://doi.org/10.1200/JCO.1996.14.8.2280 CrossRefPubMedGoogle Scholar
  50. 50.
    Venook AP, Niedzwiecki D, Lenz HJ et al (2017) Effect of first-line chemotherapy combined With Cetuximab or Bevacizumab on overall survival in patients with kras wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA 317(23):2392–2401.  https://doi.org/10.1001/jama.2017.7105 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Maughan TS, Adams RA, Smith CG et al (2011) Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377(9783):2103–2114.  https://doi.org/10.1016/S0140-6736(11)60613-2 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Maughan TS, James RD, Kerr DJ et al (2002) Comparison of survival, palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial. Lancet 359(9317):1555–1563.  https://doi.org/10.1016/s0140-6736(02)08514-8 CrossRefPubMedGoogle Scholar
  53. 53.
    Heinemann V, von Weikersthal LF, Decker T et al (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 15(10):1065–1075.  https://doi.org/10.1016/S1470-2045(14)70330-4 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Loupakis F, Cremolini C, Masi G et al (2014) Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 371(17):1609–1618.  https://doi.org/10.1056/NEJMoa1403108 CrossRefPubMedGoogle Scholar
  55. 55.
    Douillard JY, Oliner KS, Siena S et al (2013) Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369(11):1023–1034.  https://doi.org/10.1056/NEJMoa1305275 CrossRefPubMedGoogle Scholar
  56. 56.
    Tol J, Koopman M, Cats A et al (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360(6):563–572.  https://doi.org/10.1056/NEJMoa0808268 CrossRefPubMedGoogle Scholar
  57. 57.
    Van Cutsem E, Köhne CH, Hitre E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360(14):1408–1417.  https://doi.org/10.1056/NEJMoa0805019 CrossRefPubMedGoogle Scholar
  58. 58.
    Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342.  https://doi.org/10.1056/NEJMoa032691 CrossRefPubMedGoogle Scholar
  59. 59.
    Saltz LB, Cox JV, Blanke C et al (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343(13):905–914.  https://doi.org/10.1056/NEJM200009283431302 CrossRefPubMedGoogle Scholar
  60. 60.
    Ocvirk J, Brodowicz T, Wrba F et al (2010) Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. World J Gastroenterol 16(25):3133–3143.  https://doi.org/10.3748/wjg.v16.i25.3133 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Cunningham D, Lang I, Marcuello E et al (2013) Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 14(11):1077–1085.  https://doi.org/10.1016/S1470-2045(13)70154-2 CrossRefPubMedGoogle Scholar
  62. 62.
    Goldberg RM, Sargent DJ, Morton RF et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22(1):23–30.  https://doi.org/10.1200/JCO.2004.09.046 CrossRefPubMedGoogle Scholar
  63. 63.
    Yamazaki K, Nagase M, Tamagawa H et al (2016) Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G). Ann Oncol 27(8):1539–1546.  https://doi.org/10.1093/annonc/mdw206 CrossRefPubMedGoogle Scholar
  64. 64.
    García-Carbonero R, van Cutsem E, Rivera F et al (2017) Randomized phase II trial of Parsatuzumab (Anti-EGFL7) or placebo in combination with FOLFOX and Bevacizumab for first-line metastatic colorectal cancer. Oncologist 22(4):375–e30.  https://doi.org/10.1634/theoncologist.2016-0133 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Pinter T, Klippel Z, Cesas A et al (2017) A phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim in patients receiving first-line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for locally advanced or metastatic colorectal cancer: final results of the Pegfilgrastim and Anti-VEGF evaluation study (PAVES). Clin Colorectal Cancer 16(2):103–14.  https://doi.org/10.1016/j.clcc.2016.08.008 CrossRefPubMedGoogle Scholar
  66. 66.
    Shi Q, De Gramont A, Grothey A et al (2015) Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database. J Clin Oncol 33(1):22.  https://doi.org/10.1200/JCO.2014.56.5887 CrossRefPubMedGoogle Scholar
  67. 67.
    Heinemann V, Stintzing S, Modest DP et al (2015) Early tumour shrinkage (ETS) and depth of response (DpR) in the treatment of patients with metastatic colorectal cancer (mCRC). Eur J Cancer 51(14):1927–36.  https://doi.org/10.1016/j.ejca.2015.06.116 CrossRefPubMedGoogle Scholar
  68. 68.
    Topalian SL, Sznol M, McDermott DF et al (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32(10):1020–30.  https://doi.org/10.1200/JCO.2013.53.0105 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Daud A, Ribas A, Robert C et al (2015) Long-term efficacy of pembrolizumab pembro MK-3475 in a pooled analysis of 655 patients with advanced melanoma MEL enrolled in KEYNOTE001. ASCO Meet Abstr 33(15):9005. https://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.9005

Copyright information

© Japan Society of Clinical Oncology 2020

Authors and Affiliations

  1. 1.Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical SciencesKitasato UniversityTokyoJapan
  2. 2.MSD K.K., a Subsidiary of Merck & Co., IncKenilworthUSA

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