リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Correlation between overall survival and surrogate endpoint in clinical trials for anticancer drugs considering tumor shrinkage」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Correlation between overall survival and surrogate endpoint in clinical trials for anticancer drugs considering tumor shrinkage

吉田 洋介 北里大学

2021.07.20

概要

Overall survival (OS) is the most reliable endpoint to assess clinical benefit of cancer patients. However, OS assessment generally requires a large sample size and long-term survival follow-up of patients. Although intermediate endpoints such as progression-free survival (PFS) and objective response rate (ORR) are broadly employed to assess drug efficacy and clinical benefit of patients earlier, none of them has been validated as a surrogate endpoint for OS. Endpoints originated from the concept of tumor shrinkage dynamics, such as early tumor shrinkage (ETS) and depth of response (DpR), were reported to be strongly associated with OS in patients with colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). In addition, a combinatory endpoint of ETS and DpR with PFS showed a stronger correlation with OS compared to the correlations between OS and either ETS or DpR. Based on these findings, we conducted a research to investigate the impact of advantage in tumor response on the correlation between treatment effects on PFS and OS in clinical trials with CRC patients (Research 1) and NSCLC patients (Research 2).

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

In Research 1, forty-seven trials with a total of 24,018 patients were identified. The hazard ratio (HR) for PFS showed a relatively higher correlation with HR 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).

In Research 2, sixty trials with a total of 29,134 patients were identified. The HR for PFS showed a relatively higher correlation with HR for OS (rs=0.75) when the trials were limited to those demonstrated a larger advantage in ORR, compared to the case for trials that demonstrated a smaller advantage (rs=0.66). This tendency was also observed in the subgroup analysis stratified by the types of treatment agents (non-targeted,
anti-angiogenic, and immunotherapy) except for the group of EGFR-targeted agents.

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

この論文で使われている画像

参考文献

1. Collaboration GBoDC (2019) Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncology 5 (12):1749-1768. doi:10.1001/jamaoncol.2019.2996

2. Siegel RL, Miller KD, Goding Sauer A et al. (2020) Colorectal cancer statistics, 2020. CA: A Cancer Journal for Clinicians 70 (3):145-164. doi:https://doi.org/10.3322/caac.21601

3. Torre LA, Siegel RL, Jemal A (2016) Lung Cancer Statistics. Adv Exp Med Biol 893:1-19. doi:10.1007/978-3-319-24223-1_1

4. Hay M, Thomas DW, Craighead JL et al. (2014) Clinical development success rates for investigational drugs. Nature Biotechnology 32 (1):40-51. doi:10.1038/nbt.2786

5. Wouters OJ, McKee M, Luyten J (2020) Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA 323 (9):844-853. doi:10.1001/jama.2020.1166

6. U.S. Department of Health and Human Services FaDA (2018) Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics. Guidance for Industry. Guidance document

7. Seruga B, Ocana A, Amir E et al. (2015) Failures in Phase III: Causes and Consequences. Clinical Cancer Research 21 (20):4552-4560. doi:10.1158/1078-0432.Ccr-15-0124

8. Douaiher J, Ravipati A, Grams B et al. (2017) Colorectal cancer—global burden, trends, and geographical variations. Journal of Surgical Oncology 115 (5):619-630. doi:10.1002/jso.24578

9. 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. Journal of Clinical Oncology 32 (21):2240-2247. doi:10.1200/jco.2013.53.2473

10. 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. The Lancet Oncology 17 (10):1426-1434. doi:https://doi.org/10.1016/S1470-2045(16)30269-8

11. 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. European Journal of Cancer 106:196-211. doi:https://doi.org/10.1016/j.ejca.2018.11.012

12. 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. Journal of Clinical Oncology 31 (30):3764-3775. doi:10.1200/jco.2012.42.8532

13. 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. Journal of Clinical Oncology 31 (15_suppl):3630-3630. doi:10.1200/jco.2013.31.15_suppl.3630

14. 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. Annals of Oncology 26 (6):1188-1194. doi:https://doi.org/10.1093/annonc/mdv112

15. Douillard J-Y, 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. European Journal of Cancer 51 (10):1231-1242. doi:https://doi.org/10.1016/j.ejca.2015.03.026

16. 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). Targeted Oncology 11 (6):799-806. doi:10.1007/s11523-016-0445-6

17. 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. European Journal of Cancer 51 (7):800-807. doi:https://doi.org/10.1016/j.ejca.2015.02.011

18. 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 Science 107 (10):1492-1498. doi:10.1111/cas.13023

19. 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. Annals of Internal Medicine 162 (11):777-784. doi:10.7326/m14-2385

20. 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. Clinical Cancer Research 19 (1):225-235. doi:10.1158/1078-0432.Ccr-12-1515

21. Broglio KR, Berry DA (2009) Detecting an Overall Survival Benefit that Is Derived From Progression-Free Survival. JNCI: Journal of the National Cancer Institute 101 (23):1642-1649. doi:10.1093/jnci/djp369

22. Morita S, Sakamaki K, Yin G (2015) Detecting Overall Survival Benefit Derived From Survival Postprogression Rather Than Progression-Free Survival. JNCI: Journal of the National Cancer Institute 107 (8). doi:10.1093/jnci/djv133

23. 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. Journal of Clinical Oncology 26 (12):1987-1992. doi:10.1200/jco.2007.10.8407

24. 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. Journal of Clinical Oncology 25 (29):4562-4568. doi:10.1200/jco.2006.08.1935

25. 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)†. Annals of Oncology 27 (1):121-127. doi:https://doi.org/10.1093/annonc/mdv491

26. 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. Annals of Oncology 26 (6):1201-1207. doi:https://doi.org/10.1093/annonc/mdv130

27. 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. Annals of Oncology 24 (7):1769-1777. doi:https://doi.org/10.1093/annonc/mdt116

28. Labianca R, Sobrero A, Isa L et al. (2011) Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised ‘GISCAD’ trial. Annals of Oncology 22 (5):1236-1242. doi:https://doi.org/10.1093/annonc/mdq580

29. 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. Annals of Oncology 22 (7):1535-1546. doi:https://doi.org/10.1093/annonc/mdq632

30. 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. Annals of Oncology 19 (5):909-914. doi:https://doi.org/10.1093/annonc/mdm588

31. Punt CJA, 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. Annals of Oncology 13 (1):81-86. doi:https://doi.org/10.1093/annonc/mdf045

32. 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. Annals of Oncology 13 (1):87-91. doi:https://doi.org/10.1093/annonc/mdf043

33. 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 Research 30 (10):4325-4333

34. Souglakos J, Ziras N, Kakolyris S et al. (2012) Randomised phase-II trial of CAPIRI (capecitabine, irinotecan) plus bevacizumab vs FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) plus bevacizumab as first-line treatment of patients with unresectable/metastatic colorectal cancer (mCRC). British Journal of Cancer 106 (3):453-459. doi:10.1038/bjc.2011.594

35. 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 Chemotherapy and Pharmacology 75 (3):569-577. doi:10.1007/s00280-015-2676-0

36. Guan Z-Z, Xu J-M, Luo R-C 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. doi:10.5732/cjc.011.10188

37. Cao B, Li S-t, Li Z et al. (2011) Yiqi Zhuyu Decoction (益气逐瘀汤) Combined with FOLFOX-4 as first-line therapy in metastatic colorectal cancer. Chinese Journal of Integrative Medicine 17 (8):593. doi:10.1007/s11655-011-0822-z

38. 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. Clinical Cancer Research 19 (9):2541-2550. doi:10.1158/1078-0432.Ccr-13-0107

39. Douillard J-Y, Zemelka T, Fountzilas G et al. (2014) FOLFOX4 With Cetuximab vs. UFOX With Cetuximab as First-Line Therapy in Metastatic Colorectal Cancer: The Randomized Phase II FUTURE Study. Clinical Colorectal Cancer 13 (1):14-26.e11. doi:https://doi.org/10.1016/j.clcc.2013.11.009

40. 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. Clinical and Translational Oncology 14 (8):606-612. doi:10.1007/s12094-012-0843-x

41. 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. International Journal of Cancer 128 (3):682-690. doi:10.1002/ijc.25369

42. 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. Journal of Cancer Research and Clinical Oncology 135 (2):217-226. doi:10.1007/s00432-008-0454-7

43. 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). Journal of Clinical Oncology 30 (29):3596-3603. doi:10.1200/jco.2012.42.6031

44. Schmoll H-J, 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). Journal of Clinical Oncology 30 (29):3588-3595. doi:10.1200/jco.2012.42.5355

45. 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. Journal of Clinical Oncology 30 (15):1755-1762. doi:10.1200/jco.2011.38.0915

46. Douillard J-Y, 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. Journal of Clinical Oncology 28 (31):4697-4705. doi:10.1200/jco.2009.27.4860

47. 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. Journal of Clinical Oncology 28 (19):3191-3198. doi:10.1200/jco.2009.27.7723

48. 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. Journal of Clinical Oncology 26 (12):2013-2019. doi:10.1200/jco.2007.14.9930

49. Porschen R, Arkenau H-T, 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. Journal of Clinical Oncology 25 (27):4217-4223. doi:10.1200/jco.2006.09.2684

50. 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. Journal of Clinical Oncology 25 (13):1670-1676. doi:10.1200/jco.2006.09.0928

51. 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. Journal of Clinical Oncology 23 (16):3697-3705. doi:10.1200/jco.2005.05.112

52. Köhne C-H, Cutsem Ev, 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. Journal of Clinical Oncology 23 (22):4856-4865. doi:10.1200/jco.2005.05.546

53. 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. Journal of Clinical Oncology 20 (6):1519-1526. doi:10.1200/jco.2002.20.6.1519

54. 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. Journal of Clinical Oncology 14 (8):2280-2288. doi:10.1200/jco.1996.14.8.2280

55. Venook AP, Niedzwiecki D, Lenz H-J 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. doi:10.1001/jama.2017.7105

56. 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. The Lancet 377 (9783):2103-2114. doi:https://doi.org/10.1016/S0140-6736(11)60613-2

57. 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. The Lancet 359 (9317):1555-1563. doi:https://doi.org/10.1016/S0140-6736(02)08514-8

58. 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. The Lancet Oncology 15 (10):1065-1075. doi:https://doi.org/10.1016/S1470-2045(14)70330-4

59. Loupakis F, Cremolini C, Masi G et al. (2014) Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer. New England Journal of Medicine 371 (17):1609-1618. doi:10.1056/NEJMoa1403108

60. Douillard J-Y, Oliner KS, Siena S et al. (2013) Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer. New England Journal of Medicine 369 (11):1023-1034. doi:10.1056/NEJMoa1305275

61. Tol J, Koopman M, Cats A et al. (2009) Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer. New England Journal of Medicine 360 (6):563-572. doi:10.1056/NEJMoa0808268

62. Van Cutsem E, Köhne C-H, Hitre E et al. (2009) Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer. New England Journal of Medicine 360 (14):1408-1417. doi:10.1056/NEJMoa0805019

63. Hurwitz H, Fehrenbacher L, Novotny W et al. (2004) Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. New England Journal of Medicine 350 (23):2335-2342. doi:10.1056/NEJMoa032691

64. Saltz LB, Cox JV, Blanke C et al. (2000) Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal Cancer. New England Journal of Medicine 343 (13):905-914. doi:10.1056/nejm200009283431302

65. 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. doi:10.3748/wjg.v16.i25.3133

66. 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. The Lancet Oncology 14 (11):1077-1085. doi:https://doi.org/10.1016/S1470-2045(13)70154-2

67. 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. Journal of Clinical Oncology 22 (1):23-30. doi:10.1200/jco.2004.09.046

68. 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). Annals of Oncology 27 (8):1539-1546. doi:https://doi.org/10.1093/annonc/mdw206

69. 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. The Oncologist 22 (4):375-e330. doi:10.1634/theoncologist.2016-0133

70. 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). Clinical Colorectal Cancer 16 (2):103-114.e103. doi:https://doi.org/10.1016/j.clcc.2016.08.008

71. Shi Q, Gramont Ad, 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. Journal of Clinical Oncology 33 (1):22-28. doi:10.1200/jco.2014.56.5887

72. Topalian SL, Sznol M, McDermott DF et al. (2014) Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal of Clinical Oncology 32 (10):1020-1030. doi:10.1200/jco.2013.53.0105

73. Daud A, Ribas A, Robert C et al. (2015) Long-term efficacy of pembrolizumab (pembro; MK-3475) in a pooled analysis of 655 patients (pts) with advanced melanoma (MEL) enrolled in KEYNOTE-001. Journal of Clinical Oncology 33 (15_suppl):9005-9005. doi:10.1200/jco.2015.33.15_suppl.9005

74. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA: A Cancer Journal for Clinicians 69 (1):7-34. doi:10.3322/caac.21551

75. Blumenthal GM, Karuri SW, Zhang H et al. (2015) Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses. Journal of Clinical Oncology 33 (9):1008-1014. doi:10.1200/jco.2014.59.0489

76. McCoach CE, Blumenthal GM, Zhang L et al. (2017) Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small-cell lung cancer treated with a targeted therapy or immunotherapy. Ann Oncol 28 (11):2707-2714. doi:10.1093/annonc/mdx414

77. 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). European Journal of Cancer 51 (14):1927-1936. doi:https://doi.org/10.1016/j.ejca.2015.06.116

78. Yoshida Y, Kaneko M, Narukawa M (2020) 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. International Journal of Clinical Oncology. doi:10.1007/s10147-020-01619-8

79. Socinski MA, Jotte RM, Cappuzzo F et al. (2018) Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. New England Journal of Medicine 378 (24):2288-2301. doi:10.1056/NEJMoa1716948

80. Kubota K, Yoshioka H, Oshita F et al. (2017) Phase III, Randomized, Placebo-Controlled, Double-Blind Trial of Motesanib (AMG-706) in Combination With Paclitaxel and Carboplatin in East Asian Patients With Advanced Nonsquamous Non– Small-Cell Lung Cancer. Journal of Clinical Oncology 35 (32):3662-3670. doi:10.1200/jco.2017.72.7297

81. Peters S, Camidge DR, Shaw AT et al. (2017) Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer. New England Journal of Medicine 377 (9):829-838. doi:10.1056/NEJMoa1704795

82. Paz-Ares L, Tan EH, O’Byrne K et al. (2017) Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Annals of Oncology 28 (2):270-277. doi:https://doi.org/10.1093/annonc/mdw611

83. Spigel DR, Luft A, Depenbrock H et al. (2017) An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non–Small-Cell Lung Cancer. Clinical Lung Cancer 18 (5):480-488. doi:https://doi.org/10.1016/j.cllc.2017.02.002

84. Yang JJ, Zhou Q, Yan HH et al. (2017) A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. British Journal of Cancer 116 (5):568-574. doi:10.1038/bjc.2016.456

85. Wakelee H, Zvirbule Z, De Braud F et al. (2017) Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non–Small-Cell Lung Cancer. Clinical Lung Cancer 18 (1):50-59. doi:https://doi.org/10.1016/j.cllc.2016.09.013

86. Ramalingam SS, Blais N, Mazieres J et al. (2017) Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non–Small Cell Lung Cancer. Clinical Cancer Research 23 (8):1937-1944. doi:10.1158/1078-0432.Ccr-15-3069

87. Joerger M, von Pawel J, Kraff S et al. (2016) Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC)†. Annals of Oncology 27 (10):1895-1902. doi:https://doi.org/10.1093/annonc/mdw290

88. Novello S, Scagliotti G, de Castro G et al. (2017) An Open-Label, Multicenter, Randomized, Phase II Study of Cisplatin and Pemetrexed With or Without Cixutumumab (IMC-A12) as a First-Line Therapy in Patients With Advanced Nonsquamous Non–Small Cell Lung Cancer. Journal of Thoracic Oncology 12 (2):383-389. doi:https://doi.org/10.1016/j.jtho.2016.07.013

89. Hirsch FR, Govindan R, Zvirbule Z et al. (2017) Efficacy and Safety Results From a Phase II, Placebo-Controlled Study of Onartuzumab Plus First-Line Platinum-Doublet Chemotherapy for Advanced Squamous Cell Non–Small-Cell Lung Cancer. Clinical Lung Cancer 18 (1):43-49. doi:https://doi.org/10.1016/j.cllc.2016.05.011

90. Yang JC-H, Srimuninnimit V, Ahn M-J et al. (2016) First-Line Pemetrexed plus Cisplatin followed by Gefitinib Maintenance Therapy versus Gefitinib Monotherapy in East Asian Never-Smoker Patients with Locally Advanced or Metastatic Nonsquamous Non–Small Cell Lung Cancer: Final Overall Survival Results from a Randomized Phase 3 Study. Journal of Thoracic Oncology 11 (3):370-379. doi:https://doi.org/10.1016/j.jtho.2015.11.008

91. Zhou C, Wu Y-L, Chen G et al. (2015) BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 33 (19):2197-2204. doi:10.1200/jco.2014.59.4424

92. Zinner RG, Obasaju CK, Spigel DR et al. (2015) PRONOUNCE: Randomized, Open-Label, Phase III Study of First-Line Pemetrexed + Carboplatin Followed by Maintenance Pemetrexed versus Paclitaxel + Carboplatin + Bevacizumab Followed by Maintenance Bevacizumab in Patients ith Advanced Nonsquamous Non–Small-Cell Lung Cancer. Journal of Thoracic Oncology 10 (1):134-142. doi:https://doi.org/10.1097/JTO.0000000000000366

93. Seto T, Kato T, Nishio M et al. (2014) Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. The Lancet Oncology 15 (11):1236-1244. doi:https://doi.org/10.1016/S1470-2045(14)70381-X

94. von Pawel J, Gorbounova V, Reck M et al. (2014) DISRUPT: A randomised phase 2 trial of ombrabulin (AVE8062) plus a taxane–platinum regimen as first-line therapy for metastatic non-small cell lung cancer. Lung Cancer 85 (2):224-229. doi:https://doi.org/10.1016/j.lungcan.2014.05.013

95. Belani CP, Yamamoto N, Bondarenko IM et al. (2014) Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. BMC Cancer 14 (1):290. doi:10.1186/1471-2407-14-290

96. Yu H, Zhang J, Wu X et al. (2014) A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer. Cancer Biology & Therapy 15 (7):832-839. doi:10.4161/cbt.28874

97. Twelves C, Chmielowska E, Havel L et al. (2014) Randomised phase II study of axitinib or bevacizumab combined with paclitaxel/carboplatin as first-line therapy for patients with advanced non-small-cell lung cancer. Annals of Oncology 25 (1):132-138. doi:https://doi.org/10.1093/annonc/mdt489

98. Patel JD, Socinski MA, Garon EB et al. (2013) PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 31 (34):4349-4357. doi:10.1200/jco.2012.47.9626

99. Wu Y-L, Lee JS, Thongprasert S et al. (2013) Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. The Lancet Oncology 14 (8):777-786. doi:https://doi.org/10.1016/S1470-2045(13)70254-7

100. Bonomi PD, Mace J, Mandanas RA et al. (2013) Randomized Phase II Study of Cetuximab and Bevacizumab in Combination with Two Regimens of Paclitaxel and Carboplatin in Chemonaive Patients with Stage IIIB/IV Non–Small-Cell Lung Cancer. Journal of Thoracic Oncology 8 (3):338-345. doi:https://doi.org/10.1097/JTO.0b013e318282ded5

101. Paz-Ares L, Bálint B, de Boer RH et al. (2013) A Randomized Phase 2 Study of Paclitaxel and Carboplatin with or without Conatumumab for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer. Journal of Thoracic Oncology 8 (3):329-337. doi:https://doi.org/10.1097/JTO.0b013e31827ce554

102. Lee SY, Park HS, Lee KY et al. (2013) Paclitaxel-Loaded Polymeric Micelle (230 mg/m2) and Cisplatin (60 mg/m2) vs. Paclitaxel (175 mg/m2) and Cisplatin (60 mg/m2) in Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase IIB Trial. Clinical Lung Cancer 14 (3):275-282. doi:https://doi.org/10.1016/j.cllc.2012.11.005

103. Paz-Ares LG, Biesma B, Heigener D et al. (2012) Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Gemcitabine/Cisplatin Alone or With Sorafenib for the First-Line Treatment of Advanced, Nonsquamous Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 30 (25):3084-3092. doi:10.1200/jco.2011.39.7646

104. Scagliotti GV, Vynnychenko I, Park K et al. (2012) International, Randomized, Placebo-Controlled, Double-Blind Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer: MONET1. Journal of Clinical Oncology 30 (23):2829-2836. doi:10.1200/jco.2011.41.4987

105. Lynch TJ, Bondarenko I, Luft A et al. (2012) Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study. Journal of Clinical Oncology 30 (17):2046-2054. doi:10.1200/jco.2011.38.4032

106. Socinski MA, Bondarenko I, Karaseva NA et al. (2012) Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial. Journal of Clinical Oncology 30 (17):2055-2062. doi:10.1200/jco.2011.39.5848

107. Niho S, Kunitoh H, Nokihara H et al. (2012) Randomized phase II study of first-line carboplatin-paclitaxel with or without bevacizumab in Japanese patients with advanced non-squamous non-small-cell lung cancer. Lung Cancer 76 (3):362-367. doi:https://doi.org/10.1016/j.lungcan.2011.12.005

108. Groen HJM, Sietsma H, Vincent A et al. (2011) Randomized, Placebo-Controlled Phase III Study of Docetaxel Plus Carboplatin With Celecoxib and Cyclooxygenase-2 Expression As a Biomarker for Patients With Advanced Non–Small-Cell Lung Cancer: The NVALT-4 Study. Journal of Clinical Oncology 29 (32):4320-4326. doi:10.1200/jco.2011.35.5214

109. Jr PNL, Douillard J-Y, Nakagawa K et al. (2011) Randomized Phase III Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the Vascular Disrupting Agent Vadimezan (ASA404) in Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 29 (22):2965-2971. doi:10.1200/jco.2011.35.0660

110. Hirsh V, Paz-Ares L, Boyer M et al. (2011) Randomized Phase III Trial of Paclitaxel/Carboplatin With or Without PF-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment for Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 29 (19):2667-2674. doi:10.1200/jco.2010.32.8971

111. Koch A, Bergman B, Holmberg E et al. (2011) Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group. European Journal of Cancer 47 (10):1546-1555. doi:https://doi.org/10.1016/j.ejca.2011.03.035

112. Digumarti R, Wang Y, Raman G et al. (2011) A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral Talactoferrin in Combination with Carboplatin and Paclitaxel in Previously Untreated Locally Advanced or Metastatic Non-small Cell Lung Cancer. Journal of Thoracic Oncology 6 (6):1098-1103. doi:https://doi.org/10.1097/JTO.0b013e3182156250

113. Manegold C, van Zandwijk N, Szczesna A et al. (2012) A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Annals of Oncology 23 (1):72-77. doi:https://doi.org/10.1093/annonc/mdr030

114. Blumenschein Jr GR, Kabbinavar F, Menon H et al. (2011) A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Annals of Oncology 22 (9):2057-2067. doi:https://doi.org/10.1093/annonc/mdq731

115. Scagliotti G, Novello S, Pawel Jv et al. (2010) Phase III Study of Carboplatin and Paclitaxel Alone or With Sorafenib in Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 28 (11):1835-1842. doi:10.1200/jco.2009.26.1321

116. Reck M, von Pawel J, Zatloukal P et al. (2010) Overall survival with cisplatin– gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Annals of Oncology 21 (9):1804-1809. doi:https://doi.org/10.1093/annonc/mdq020

117. Lynch TJ, Patel T, Dreisbach L et al. (2010) Cetuximab and First-Line Taxane/Carboplatin Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the Randomized Multicenter Phase III Trial BMS099. Journal of Clinical Oncology 28 (6):911-917. doi:10.1200/jco.2009.21.9618

118. Takeda K, Hida T, Sato T et al. (2010) Randomized Phase III Trial of Platinum-Doublet Chemotherapy Followed by Gefitinib Compared With Continued Platinum-Doublet Chemotherapy in Japanese Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Thoracic Oncology Group Trial (WJTOG0203). Journal of Clinical Oncology 28 (5):753-760. doi:10.1200/jco.2009.23.3445

119. Lee SM, Rudd R, Woll PJ et al. (2009) Randomized Double-Blind Placebo-Controlled Trial of Thalidomide in Combination With Gemcitabine and Carboplatin in Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 27 (31):5248-5254. doi:10.1200/jco.2009.21.9733

120. Zwitter M, Kovac V, Smrdel U et al. (2009) Gemcitabine in Brief versus Prolonged Low-Dose Infusion, both Combined with Cisplatin, for Advanced Non-small Cell Lung Cancer: A Randomized Phase II Clinical Trial. Journal of Thoracic Oncology 4 (9):1148-1155. doi:https://doi.org/10.1097/JTO.0b013e3181ae280f

121. Comella P, Chiuri VE, De Cataldis G et al. (2010) Gemcitabine combined with either pemetrexed or paclitaxel in the treatment of advanced non-small cell lung cancer: A randomized phase II SICOG trial. Lung Cancer 68 (1):94-98. doi:https://doi.org/10.1016/j.lungcan.2009.05.008

122. Goss G, Ferry D, Wierzbicki R et al. (2009) Randomized Phase II Study of Gefitinib Compared With Placebo in Chemotherapy-Naive Patients With Advanced Non–Small-Cell Lung Cancer and Poor Performance Status. Journal of Clinical Oncology 27 (13):2253-2260. doi:10.1200/jco.2008.18.4408

123. Kubota K, Kawahara M, Ogawara M et al. (2008) Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. The Lancet Oncology 9 (12):1135-1142. doi:https://doi.org/10.1016/S1470-2045(08)70261-4

124. Heymach JV, Paz-Ares L, Braud FD et al. (2008) Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology 26 (33):5407-5415. doi:10.1200/jco.2008.17.3138

125. Crinò L, Cappuzzo F, Zatloukal P et al. (2008) Gefitinib Versus Vinorelbine in Chemotherapy-Naïve Elderly Patients With Advanced Non–Small-Cell Lung Cancer (INVITE): A Randomized, Phase II Study. Journal of Clinical Oncology 26 (26):4253-4260. doi:10.1200/jco.2007.15.0672

126. Gridelli C, Gallo C, Ceribelli A et al. (2007) Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. The Lancet Oncology 8 (6):500-512. doi:https://doi.org/10.1016/S1470-2045(07)70146-8

127. Gatzemeier U, Pluzanska A, Szczesna A et al. (2007) Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial. Journal of Clinical Oncology 25 (12):1545-1552. doi:10.1200/jco.2005.05.1474

128. Sandler A, Gray R, Perry MC et al. (2006) Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer. New England Journal of Medicine 355 (24):2542-2550. doi:10.1056/NEJMoa061884

129. Mok TSK, Wu Y-L, Kudaba I et al. (2019) Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. The Lancet 393 (10183):1819-1830. doi:https://doi.org/10.1016/S0140-6736(18)32409-7

130. Herbst RS, Redman MW, Kim ES et al. (2018) Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. The Lancet Oncology 19 (1):101-114. doi:https://doi.org/10.1016/S1470-2045(17)30694-0

131. Thatcher N, Hirsch FR, Luft AV et al. (2015) Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. The Lancet Oncology 16 (7):763-774. doi:https://doi.org/10.1016/S1470-2045(15)00021-2

132. Paz-Ares L, Mezger J, Ciuleanu TE et al. (2015) Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. The Lancet Oncology 16 (3):328-337. doi:https://doi.org/10.1016/S1470-2045(15)70046-X

133. von Pawel J, Spigel DR, Ervin T et al. (2018) Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First-Line Nonsquamous Non-Small Cell Lung Cancer. The Oncologist 23 (6):654-e658. doi:10.1634/theoncologist.2017-0690

134. Gridelli C, Perrone F, Gallo C et al. (2003) Chemotherapy for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Multicenter Italian Lung Cancer in the Elderly Study (MILES) Phase III Randomized Trial. JNCI: Journal of the National Cancer Institute 95 (5):362-372. doi:10.1093/jnci/95.5.362

135. Hellmann MD, Paz-Ares L, Bernabe Caro R et al. (2019) Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer. New England Journal of Medicine 381 (21):2020-2031. doi:10.1056/NEJMoa1910231

136. Mok TS, Cheng Y, Zhou X et al. (2018) Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer and EGFR-Activating Mutations. Journal of Clinical Oncology 36 (22):2244-2250. doi:10.1200/jco.2018.78.7994

137. Dingemans AMC, Groen HJM, Herder GJM et al. (2015) A randomized phase II study comparing paclitaxel–carboplatin–bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†. Annals of Oncology 26 (11):2286-2293. doi:https://doi.org/10.1093/annonc/mdv370

138. Thomas M, Fischer J, Andreas S et al. (2015) Erlotinib and bevacizumab <em>versus</em> cisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer. European Respiratory Journal 46 (1):219-229. doi:10.1183/09031936.00229014

139. Nakashima K, Horita N, Nagai K et al. (2016) Progression-Free Survival, Response Rate, and Disease Control Rate as Predictors of Overall Survival in Phase III Randomized Controlled Trials Evaluating the First-Line Chemotherapy for Advanced, Locally Advanced, and Recurrent Non–Small Cell Lung Carcinoma. Journal of Thoracic Oncology 11 (9):1574-1585. doi:https://doi.org/10.1016/j.jtho.2016.04.025

140. Hotta K, Suzuki E, Di Maio M et al. (2013) Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer. Lung Cancer 79 (1):20-26. doi:https://doi.org/10.1016/j.lungcan.2012.10.007

141. Ritchie G, Gasper H, Man J et al. (2018) Defining the Most Appropriate Primary End Point in Phase 2 Trials of Immune Checkpoint Inhibitors for Advanced Solid Cancers: A Systematic Review and Meta-analysis. JAMA Oncology 4 (4):522-528. doi:10.1001/jamaoncol.2017.5236

142. Ito K, Miura S, Sakaguchi T et al. (2019) The impact of high PD-L1 expression on the surrogate endpoints and clinical outcomes of anti-PD-1/PD-L1 antibodies in non-small cell lung cancer. Lung Cancer 128:113-119. doi:https://doi.org/10.1016/j.lungcan.2018.12.023

143. Nie R-C, Chen F-P, Yuan S-Q et al. (2019) Evaluation of objective response, disease control and progression-free survival as surrogate end-points for overall survival in anti–programmed death-1 and anti–programmed death ligand 1 trials. European Journal of Cancer 106:1-11. doi:https://doi.org/10.1016/j.ejca.2018.10.011

144. Gyawali B, Hey SP, Kesselheim AS (2018) A Comparison of Response Patterns for Progression-Free Survival and Overall Survival Following Treatment for Cancer With PD-1 Inhibitors: A Meta-analysis of Correlation and Differences in Effect Sizes. JAMA Netw Open 1 (2):e180416. doi:10.1001/jamanetworkopen.2018.0416

145. Kaufman HL, Schwartz LH, William WN, Jr. et al. (2018) Evaluation of classical clinical endpoints as surrogates for overall survival in patients treated with immune checkpoint blockers: a systematic review and meta-analysis. J Cancer Res Clin Oncol 144 (11):2245-2261. doi:10.1007/s00432-018-2738-x

146. Morgensztern D, Ko A, O’Brien M et al. (2019) Association between depth of response and survival in patients with advanced-stage non–small cell lung cancer treated with first-line chemotherapy. Cancer 125 (14):2394-2399. doi:10.1002/cncr.32114

147. Kawachi H, Fujimoto D, Morimoto T et al. (2019) Early depth of tumor shrinkage and treatment outcomes in non-small cell lung cancer treated using Nivolumab. Investigational New Drugs 37 (6):1257-1265. doi:10.1007/s10637-019-00770-y

148. Lee CK, Lord S, Marschner I et al. (2018) The Value of Early Depth of Response in Predicting Long-Term Outcome in EGFR-Mutant Lung Cancer. Journal of Thoracic Oncology 13 (6):792-800. doi:https://doi.org/10.1016/j.jtho.2018.03.010

149. Takeda M, Okamoto I, Nakagawa K (2014) Survival Outcome Assessed According to Tumor Response and Shrinkage Pattern in Patients with EGFR Mutation–Positive Non–Small-Cell Lung Cancer Treated with Gefitinib or Erlotinib. Journal of Thoracic Oncology 9 (2):200-204. doi:https://doi.org/10.1097/JTO.0000000000000053

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る