Assessment of benefits and risks in development of targeted therapies for cancer - The view of regulatory authorities

Molecular Oncology

Volumn 9, Issue 5, 2015, Pages 1034-1041

  Pignatti, Francesco ^a   Jonsson, Bertil ^b   Blumenthal, Gideon ^c   Justice, Robert ^c  

^a EUROPEAN MEDICINES AGENCY   (United Kingdom)

^b MEDICAL PRODUCTS AGENCY   (Sweden)

^c CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

Benefit risk balance; Drug regulation; Targeted therapies

Indexed keywords

BEVACIZUMAB; BIOLOGICAL MARKER; CETUXIMAB; ERLOTINIB; GEFITINIB; PANITUMUMAB; VANDETANIB; ANTINEOPLASTIC AGENT;

ABDOMINAL PAIN; ACNE; ANAPHYLAXIS; ARTERIAL THROMBOEMBOLISM; BLEEDING; CLINICAL TRIAL (TOPIC); CONGESTIVE HEART FAILURE; CONSTIPATION; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DRUG APPROVAL; FOOD AND DRUG ADMINISTRATION; GOVERNMENT REGULATION; HEADACHE; HEART FAILURE; HUMAN; HYPERTENSION; HYPOMAGNESEMIA; INFECTION; INTESTINE PERFORATION; LUNG FIBROSIS; MOLECULARLY TARGETED THERAPY; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PERFORATION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RASH; REVIEW; RISK BENEFIT ANALYSIS; RISK MANAGEMENT; SENSORY NEUROPATHY; SIDE EFFECT; SKIN TOXICITY; STOMACH PERFORATION; STOMATITIS; VOMITING; WOUND HEALING IMPAIRMENT; NEOPLASMS; RISK ASSESSMENT;

ANTINEOPLASTIC AGENTS; HUMANS; NEOPLASMS; RISK ASSESSMENT;

EID: 84928585330     PISSN: 15747891     EISSN: 18780261     Source Type: Journal    
DOI: 10.1016/j.molonc.2014.10.003     Document Type: Review

References (63)

1. Amado R.G., Wolf M., Peeters M., Van Cutsem E., Siena S., Freeman D.J., et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J.Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2008, 26(10):1626-1634. Epub 2008/03/05. PubMed PMID: 18316791. 10.1200/JCO.2007.14.7116.
2. Barker A.D., Sigman C.C., Kelloff G.J., Hylton N.M., Berry D.A., Esserman L.J. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin. Pharmacol. Ther. 2009, 86(1):97-100. Epub 2009/05/15. PubMed PMID: 19440188. 10.1038/clpt.2009.68.
3. Bremnes R.M., Andersen K., Wist E.A. Cancer patients, doctors and nurses vary in their willingness to undertake cancer chemotherapy. Eur. J. Cancer 1995, 31A(12):1955-1959. Epub 1995/11/01. PubMed PMID: 8562147.
4. CFR 312.84 - Risk-benefit Analysis in Review of Marketing Applications for Drugs to Treat Life-threatening and Severely-debilitating Illnesses 1988.
5. Chinot O.L., Wick W., Mason W., Henriksson R., Saran F., Nishikawa R., et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. New Engl. J. Med. 2014, 370(8):709-722. Epub 2014/02/21. PubMed PMID: 24552318. 10.1056/NEJMoa1308345.
6. ClinicalTrials.gov Imatinib in Patients with Desmoid Tumor and Chondrosarcoma (Basket 1) (NCT00928525) 2014.
7. Cohen M.H., Shen Y.L., Keegan P., Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist 2009, 14(11):1131-1138. Epub 2009/11/10. PubMed PMID: 19897538. 10.1634/theoncologist.2009-0121.
8. Cunningham D., Humblet Y., Siena S., Khayat D., Bleiberg H., Santoro A., et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New Engl. J. Med. 2004, 351(4):337-345. Epub 2004/07/23. PubMed PMID: 15269313. 10.1056/NEJMoa033025.
9. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code Relating to Medicinal Products for Human Use 2001.
10. Eichler H.G., Pignatti F., Flamion B., Leufkens H., Breckenridge A. Balancing early market access to new drugs with the need for benefit/risk data: a mounting dilemma. Nat. Rev. Drug Discov. 2008, 7(10):818-826. Epub 2008/09/13. PubMed PMID: 18787530. 10.1038/nrd2664.
11. Eichler H.G., Abadie E., Raine J.M., Salmonson T. Safe drugs and the cost of good intentions. New Engl. J. Med. 2009, 360(14):1378-1380. Epub 2009/04/03. PubMed PMID: 19339718. 10.1056/NEJMp0900092.
12. Eichler H.G., Oye K., Baird L.G., Abadie E., Brown J., Drum C.L., et al. Adaptive licensing: taking the next step in the evolution of drug approval. Clin. Pharmacol. Ther. 2012, 91(3):426-437. Epub 2012/02/18. PubMed PMID: 22336591. 10.1038/clpt.2011.345.
13. European Medicines Agency Assessment Report for Erbitux 2006, Available from:. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000558/WC500029113.pdf.
14. European Medicines Agency Assessment Report for Vectibix 2007, Available from:. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000741/WC500047707.pdf.
15. European Medicines Agency Assessment Report for Tarceva 2007, Available from:. http://www.ema.europa.eu/ema/index.jsp?curl%3Dpages/medicines/human/medicines/000618/human_med_001077.jsp%26mid%3DWC0b01ac058001d124.
16. European Medicines Agency Assessment Report for Iressa 2009, Available from:. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001016/WC500036361.pdf.
17. European Medicines Agency Committee for Human Medicinal Products. Reflection Paper on Methodological Issues with Pharmacogenomic Biomarkers in Relation to Clinical Development and Patient Selection (Draft). 2011 Jun 2010, The Agency, London.
18. European Medicines Agency Refusal Assessment Report for AVASTIN 2010, Available from:. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000582/WC500075000.pdf.
19. European Medicines Agency Assessment Report for AVASTIN 2011, Available from:. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000582/WC500105601.pdf.
20. European Medicines Agency CHMP Assessment Report: Xalkori (Crizotinib). 2012 Jul 2012, The Agency, London.
21. European Medicines Agency Assessment Report for Caprelsa 2012, Available from:. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002315/WC500123603.pdf.
22. European Medicines Agency, Oncology Working Party Guideline on the Evaluation of Anticancer Medicinal Products in man.; 2012 Dec 2013, The Agency, London.
23. European Medicines Agency CHMP Assessment Report: Vectibix (Panitumumab) 2007 Dec, The Agency, London.
24. European Medicines Agency Refusal of a change to the marketing authorisation for Avastin (bevacizumab) 2014, Available from:. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opin.
25. Federal Food, Drug, and Cosmetic Act, Subchapter V, Part A 1938.
26. Food and Drug Administration Guidance for Industry - Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics 2007, Available from:. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071590.pdf.
27. Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration Staff - InVitro Companion Diagnostic Devices 2011, Available from:. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM262327.pdf.
28. Food and Drug Administration Structured Approach to Benefit-risk Assessment in Drug Regulatory Decision-making 2013, PDUFA V Plan (FY 2013-2017). Draft of February 2013, Available from:. http://patientnetwork.fda.gov/sites/default/files/fda_benefit-risk_draft_plan_final_for_posting.pdf.
29. Genetic Alliance UK New Medicines for Seriouis Conditions. Weighing the Benefits and Risks - The Verdict of a Jury of Patients 2012, Available from:. http://www.geneticalliance.org.uk/docs/citizens-jury-report.pdf.
30. Giusti R.M., Shastri K.A., Cohen M.H., Keegan P., Pazdur R. FDA drug approval summary: panitumumab (Vectibix). Oncologist 2007, 12(5):577-583. Epub 2007/05/25. PubMed PMID: 17522246. 10.1634/theoncologist.12-5-577.
31. Harmon A. New drugs stir debate on rules of clinical trials. The New York Times 2010 September 18, (Sect. Target Cancer).
32. Hirose T., Horichi N., Ohmori T., Kusumoto S., Sugiyama T., Shirai T., et al. Patients preferences in chemotherapy for advanced non-small-cell lung cancer. Intern. Med. 2005, 44(2):107-113. Epub 2005/03/08. PubMed PMID: 15750269.
33. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. (ICH). Harmonised Tripartite Guideline Statistical Principles for Clinical Trials (E9) 1998.
34. Johnson J.R., Williams G., Pazdur R. End points and United States Food and Drug Administration approval of oncology drugs. J.Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2003, 21(7):1404-1411. Epub 2003/03/29. PubMed PMID: 12663734.
35. Johnson F.R., Hauber B., Ozdemir S., Siegel C.A., Hass S., Sands B.E. Are gastroenterologists less tolerant of treatment risks than patients? Benefit-risk preferences in Crohn's disease management. J.Manag. Care Pharm. 2010, 16(8):616-628. Epub 2010/09/28. PubMed PMID: 20866166.
36. Johnson J.R., Ning Y.M., Farrell A., Justice R., Keegan P., Pazdur R. Accelerated approval of oncology products: the food and drug administration experience. J.Natl. Cancer Inst. 2011, 103(8):636-644. Epub 2011/03/23. PubMed PMID: 21422403. 10.1093/jnci/djr062.
37. Kim E.S., Hirsh V., Mok T., Socinski M.A., Gervais R., Wu Y.L., et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008, 372(9652):1809-1818. Epub 2008/11/26. PubMed PMID: 19027483. 10.1016/S0140-6736(08)61758-4.
38. Kim E.S., Herbst R.S., Wistuba I.I., Lee J.J., Blumenschein G.R., Tsao A., et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov. 2011, 1(1):44-53. Epub 2012/05/16. PubMed PMID: 22586319. 10.1158/2159-8274.CD-10-0010.
39. Levitan B.S., Andrews E.B., Gilsenan A., Ferguson J., Noel R.A., Coplan P.M., et al. Application of the BRAT framework to case studies: observations and insights. Clin. Pharmacol. Ther. 2011, 89(2):217-224. Epub 2010/12/24. PubMed PMID: 21178990. 10.1038/clpt.2010.280.
40. Littlejohns P. NICE at 10 years: new challenges ahead. Expert Rev. Pharmacoecon. Outcomes Res. 2009, 9(2):151-156. Epub 2009/05/01. PubMed PMID: 19402803. 10.1586/erp.09.13.
41. LUNG-MAP About Lung-MAP 2014, Available from:. http://www.lung-map.org/about-lung-map.
42. Matsuyama R., Reddy S., Smith T.J. Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J.Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2006, 24(21):3490-3496. Epub 2006/07/20. PubMed PMID: 16849766. 10.1200/JCO.2005.03.6236.
43. Miller K., Wang M., Gralow J., Dickler M., Cobleigh M., Perez E.A., et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. New Engl. J. Med. 2007, 357(26):2666-2676. Epub 2007/12/28. PubMed PMID: 18160686. 10.1056/NEJMoa072113.
44. Mok T.S., Wu Y.L., Thongprasert S., Yang C.H., Chu D.T., Saijo N., et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. New Engl. J. Med. 2009, 361(10):947-957. Epub 2009/08/21. PubMed PMID: 19692680. 10.1056/NEJMoa0810699.
45. Moore M.J., Goldstein D., Hamm J., Figer A., Hecht J.R., 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. Off. J. Am. Soc. Clin. Oncol. 2007, 25(15):1960-1966. Epub 2007/04/25. PubMed PMID: 17452677. 10.1200/JCO.2006.07.9525.
46. Mt-Isa S., Hallgreen C.E., Wang N., Callreus T., Genov G., Hirsch I., et al. Balancing benefit and risk of medicines: a systematic review and classification of available methodologies. Pharmacoepidemiol. Drug Saf. 2014, Epub 2014/05/14. PubMed PMID: 24821575. 10.1002/pds. 3636.
47. Parkinson D.R., McCormack R.T., Keating S.M., Gutman S.I., Hamilton S.R., Mansfield E.A., et al. Evidence of clinical utility: an unmet need in molecular diagnostics for patients with cancer. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2014, 20(6):1428-1444. Epub 2014/03/19. PubMed PMID: 24634466. 10.1158/1078-0432.CCR-13-2961.
48. Pazdur R. For Personalized Medicine, It's Back to the Future: Pazdur Explains SCRIP Intelligence 2013, 29 October 2013.
49. Phillips L., Fasolo B., Zafiropoulos N., Beyer A. Is quantitative benefit-risk modelling of drugs desirable or possible?. Drug Discov. Today Tech. 2011, 8(1):e3-e10.
50. Pignatti F., Gravanis I., Herold R., Vamvakas S., Jonsson B., Marty M. The European Medicines Agency: an overview of its mission, responsibilities, and recent initiatives in cancer drug regulation. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2011, 17(16):5220-5225. Epub 2011/08/17. PubMed PMID: 21844037. 10.1158/1078-0432.CCR-11-0623.
51. Pignatti F., Ehmann F., Hemmings R., Jonsson B., Nuebling M., Papaluca-Amati M., et al. Cancer drug development and the evolving regulatory framework for companion diagnostics in the European union. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2014, 20(6):1458-1468. Epub 2014/03/19. PubMed PMID: 24634469. 10.1158/1078-0432.CCR-13-1571.
52. Prowell T.M., Pazdur R. Pathological complete response and accelerated drug approval in early breast cancer. New Engl. J. Med. 2012, 366(26):2438-2441. Epub 2012/06/01. PubMed PMID: 22646508. 10.1056/NEJMp1205737.
53. Schilsky R.L. Implementing personalized cancer care. Nat. Rev. Clin. Oncol. 2014, Epub 2014/04/02. PubMed PMID: 24687035. 10.1038/nrclinonc.2014.54.
54. Sharma M.R., Schilsky R.L. Role of randomized phase III trials in an era of effective targeted therapies. Nat. Rev. Clin. Oncol. 2012, 9(4):208-214. Epub 2011/12/07. PubMed PMID: 22143142. 10.1038/nrclinonc.2011.190.
55. Slevin M.L., Stubbs L., Plant H.J., Wilson P., Gregory W.M., Armes P.J., et al. Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses, and general public. BMJ 1990, 300(6737):1458-1460. Epub 1990/06/02. PubMed PMID: 2379006; PubMed Central PMCID: PMC1663147.
56. Sridhara R., Johnson J.R., Justice R., Keegan P., Chakravarty A., Pazdur R. Review of oncology and hematology drug product approvals at the US Food and Drug Administration between July 2005 and December 2007. J.Natl. Cancer Inst. 2010, 102(4):230-243. Epub 2010/02/02. PubMed PMID: 20118413. 10.1093/jnci/djp515.
57. Tabernero, J., Chan, E., Baselga, J., Blay, J.-Y., Chau, I., Hyman, D.M., etal. VE-BASKET, a Simon 2-Stage Adaptive Design, Phase II, Histology-independent Study in Nonmelanoma Solid Tumors Harboring BRAF V600 Mutations (V600m): Activity of Vemurafenib (VEM) with or without Cetuximab (CTX) in Colorectal Cancer (CRC).
58. Thornton K., Kim G., Maher V.E., Chattopadhyay S., Tang S., Moon Y.J., et al. Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2012, 18(14):3722-3730. Epub 2012/06/06. PubMed PMID: 22665903. 10.1158/1078-0432.CCR-12-0411.
59. Tsimberidou A.M., Ringborg U., Schilsky R.L. Strategies to overcome clinical, regulatory, and financial challenges in the implementation of personalized medicine. American Society of Clinical Oncology Educational Book/ASCO American Society of Clinical Oncology Meeting 2013, 118-125. Epub 2013/05/30. PubMed PMID: 23714475. 10.1200/EdBook_AM.2013.33.118.
60. United States Food and Drug Administration. FDA Commissioner Announces Avastin Decision - Drug Not Shown to Be Safe and Effective in Breast cancer Patients 2011, Available from:. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm280536.htm.
61. Van Cutsem E., Kohne C.H., Hitre E., Zaluski J., Chang Chien C.R., Makhson A., et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. New Engl. J. Med. 2009, 360(14):1408-1417. Epub 2009/04/03. PubMed PMID: 19339720. 10.1056/NEJMoa0805019.
62. Wells S.A., Robinson B.G., Gagel R.F., Dralle H., Fagin J.A., Santoro M., et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J.Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2012, 30(2):134-141. Epub 2011/10/26. PubMed PMID: 22025146; PubMed Central PMCID: PMC3675689. 10.1200/JCO.2011.35.5040.
63. Wilson W.H., Schenkein D.P., Jernigan C.L., Woodcock J., Schilsky R.L. Reevaluating the accelerated approval process for oncology drugs. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2013, 19(11):2804-2809. Epub 2013/04/05. PubMed PMID: 23553847. 10.1158/1078-0432.CCR-13-0315.