Raising the bar for antineoplastic agents: How to choose threshold values for superiority trials in advanced solid tumors

Clinical Cancer Research

Volumn 21, Issue 5, 2015, Pages 1036-1043

  Sobrero, Alberto F ^a   Pastorino, Alessandro ^a   Sargent, Daniel J ^b   Bruzzi, Paolo ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABIRATERONE; AFATINIB; ANTINEOPLASTIC AGENT; BEVACIZUMAB; CABAZITAXEL; CETUXIMAB; ENZALUTAMIDE; ERLOTINIB; IPILIMUMAB; NEW DRUG; RADIUM; RADIUM 223; SORAFENIB; SUNITINIB; TEMSIROLIMUS; TRASTUZUMAB; UNCLASSIFIED DRUG; VEMURAFENIB;

ADVANCED CANCER; ARTICLE; BREAST CANCER; CANCER PATIENT; CANCER PROGNOSIS; CANCER SURVIVAL; COLON CANCER; CONTROLLED STUDY; DIAGNOSTIC TEST ACCURACY STUDY; DRUG EFFICACY; HEAD AND NECK CANCER; HUMAN; KIDNEY CANCER; LIVER CELL CARCINOMA; LUNG CANCER; MELANOMA; ONCOLOGICAL PARAMETERS; OUTCOME ASSESSMENT; OVARY CANCER; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL (TOPIC); PRACTICE GUIDELINE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROSTATE CANCER; RANDOMIZED CONTROLLED TRIAL (TOPIC); REFERENCE VALUE; SOLID TUMOR; STOMACH CANCER; TREATMENT RESPONSE; CANCER STAGING; CLINICAL TRIAL (TOPIC); KAPLAN MEIER METHOD; MORTALITY; NEOPLASMS; PATHOLOGY; STATISTICAL MODEL; TIME; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS AS TOPIC; HUMANS; KAPLAN-MEIER ESTIMATE; MODELS, STATISTICAL; NEOPLASM STAGING; NEOPLASMS; TIME FACTORS; TREATMENT OUTCOME;

EID: 84929464997     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-14-1505     Document Type: Article

References (51)

1. Lee J. Demystify statistical significance-time to move from the p-value to bayesian analysis. J Natl Cancer Inst 2011; 103: 2-3.
2. Ocana A, Tannock IF. When are "positive" clinical trials in oncology truly positive? J Natl Cancer Inst 2011; 103: 16-20.
3. Sobrero A, Bruzzi P. Incremental advance or seismic shift? the need to raise the bar of efficacy for drug approval. J Clin Oncol 2009; 27: 5868-73.
4. Ellis LM, Bernstein DS, Voest EE, Berlin JD, Sargent DJ, Cortazar P, et al. American Society of Clinical Oncology perspective: raising the bar for clinical trials by defining clinically meaningful outcomes. [Published online ahead of print March 17, 2014]. J Clin Oncol 2014; 32: 1277-80.
5. Sequist LV, Chih-Hsin Yang J, Yamamoto N, O'Byrne K, Hirsh V, Mok T, et al. Phase III Study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013; 31: 3327-34.
6. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, orboth for advanced renal-cell carcinoma. N Eng J Med 2007; 356: 2271-81.
7. Motzer RJ, Hutson TE, Tomczak P, Dror Michaelson R, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 3584-90.
8. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (avoren): final analysis of overall survival. J Clin Oncol 2010; 28: 2144-50.
9. Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: Final overall survival results and safety update. Eur J Cancer 2013; 49: 1287-96.
10. Motzer RJ, Escudier B, Tomczak P, Hutson TE, Dror Michaelson M, Negrier S, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 2013; 14: 552-62.
11. Motzer J, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma final results and analysis of prognostic factors. Cancer 2010; 116: 4256-65.
12. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against her2 for metastatic breast cancer that overexpresses her2. N Eng J Med 2001; 344: 783-92.
13. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Eng J Med 2007; 357: 2666-76.
14. Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 2010; 28: 3239-47.
15. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for her2-positive advanced breast cancer. N Eng J Med 2012; 367: 1783-9.
16. Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, et al. Erlotinib as maintenance treatment in advancednon-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010; 11: 521-9.
17. Shepherd FA, Pereira JR, Ciuleanu T, Eng Huat Tan, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Eng J Med 2005; 353: 123-32.
18. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Eng J Med 2006; 355: 2542-50.
19. Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Swan-Swan Leong, Sriuranpong V, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in asia (IPASS). J Clin Oncol 2011; 29: 2866-74.
20. Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Yi-Long Wuet, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008; 372: 1809-18.
21. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Myung-Ju Ahnet, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Eng J Med 2013; 368: 2385-94.
22. Demetri GD, Van Oosterom AT, Garrett CR, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368: 1329-38.
23. Hurwitz H, Fehrenbache L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Eng J Med 2004; 350: 2335-42.
24. Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovirin improves survival for patiens with metastatic colorectal cancer. J Clin Oncol 2005; 23: 3706-12.
25. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the eastern cooperative oncology group study E3200. J Clin Oncol 2007; 25: 1539-44.
26. Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, et al. Bevacizumab in combination with capecitabine for the first-line treatment of elderly patients with metastatic colorectal cancer (mCRC): Results of a randomized international phase III trial (AVEX). Lancet Oncol 2013; 14: 1077-85.
27. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26: 2013-9.
28. Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with folfiri alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 2010; 28: 4706-13.
29. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. 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 2010; 28: 4697-705.
30. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan C, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Eng J Med 2008; 359: 1757-65.
31. Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Eng J Med 2009; 360: 1408-17.
32. Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomized phase 3 trial. Lancet Oncol 2013; 14: 29-37.
33. Van Cutsem E, Tabernero J, lakomy R, Prenen H, Prausovà J, Macarulla T, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012; 30: 3499-506.
34. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303-12.
35. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. 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 2007; 25: 1960-6.
36. Von Hoff DD, Ervin T, Arena FP, Chiorean G, Infante RJ, Mooreet MJ, et al. Results of a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine vs gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas with pet and CA19-9 correlates. J Clin Oncol 31, 2013 (suppl; abstr 4005).
37. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Eng J Med 2008; 359: 378-90.
38. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Eng J Med 2006; 354: 567-78.
39. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Updated overall survival (OS) results from BRIm-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib with dacarbazine in previously untreated patients with BRAF mutated melanoma. J Clin Oncol 30, 2012 (suppl; abstr 8502).
40. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Eng J Med 2010; 363: 711-23.
41. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawakiet A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): phase 3, open-label, randomised controlled trial. Lancet 2010; 376: 687-97.
42. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Eng J Med 2011; 364: 1995-2005.
43. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or Mitoxantrone for meta-static castration-resistant prostate cancer progressing after doce-taxel treatment: a randomised open-label trial. Lancet 2010; 376: 1147-54.
44. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Eng J Med 2012; 367: 1187-97.
45. Parker C, Nilsson S, Heinrich D, Fossa SD, Chodacki A, Wiechno P, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. NEng J Med 2013; 369: 213-23.
46. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Eng J Med 2011; 365: 2484-296.
47. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. OCEANS: a randomized, double-blind, placebo-controlled phase iii trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 2012; 30: 2039-45.
48. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Eng J Med 2011; 365: 2473-83.
49. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehleret M, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 2009; 27: 3312-8.
50. Sacher AG, Lee WL, Leighl NB. Shifting pattern in the interpretation of phase III clinical trial outcomes in advanced non small cell lung cancer: the bar is dropping. [Published online ahead of print May 10, 2014]. J Clin Oncol 2014; 32: 1407-11.
51. Le Deley MC, Ballman KV, Marandet J, Sargent D. Taking the long view: howto design aseries of Phase III trialsto maximize cumulative therapeutic benefit. Clinical Trials 2012; 9: 283-92.