Real-World Evidence of Clinical Outcomes in Precision Radionuclide Oncology: The NIGHTCAP Study of 177Lu-PSMA in Metastatic Prostate Cancer

Author(s): J. Harvey Turner*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 31 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

A novel approach to current radiopharmaceutical study design to document the efficiency of 177Lu- PSMA-radioligand therapy of metastatic prostate cancer is described in a proposed prospective, real-time, realworld audit of a large patient population worldwide. The NIGHTCAP (National Investigators Global Harmonisation Theragnostics of Cancer of Prostate) Study will establish real-world evidence (RWE) of overall survival (OS) and quality of life (QoL) in patients undergoing routine 177Lu-PSMA-radioligand therapy on harmonised compassionate patient-usage protocols throughout the world. Such long-term efficiency data will be contrasted with the short-term randomised controlled trial (RCT) assessments of efficacy predicated upon surrogate markers of survival outcomes, such as progression-free survival (PFS). The shortcomings of RCT evaluation of the clinical benefit of new anticancer agents are detailed in this review, which advocates RWE to determine efficiency.

The real-time monitoring of QoL in the NIGHTCAP Study is independent of questionnaires, language differences, or oncologist bias, and relies upon individual patient self-assessment by choice of one of five emoji which best reflects their mood each day.

Keywords: Theragnostics, Real-world Data, efficiency, Lutetium-177-PSMA Radio-ligand Therapy, prostate cancer, NIGHTCAP Study.

[1]
Janiaud P, Serghiou S, Ioannidis JPA. New clinical trial designs in the era of precision medicine: An overview of definitions, strengths, weaknesses, and current use in oncology. Cancer Treat Rev 2019; 73: 20-30.
[http://dx.doi.org/10.1016/j.ctrv.2018.12.003] [PMID: 30572165]
[2]
Gerwing M, Herrmann K, Helfen A, et al. The beginning of the end for conventional RECIST - novel therapies require novel imaging approaches. Nat Rev Clin Oncol 2019; 16(7): 442-58.
[http://dx.doi.org/10.1038/s41571-019-0169-5] [PMID: 30718844]
[3]
ICH guidelines E8(R1) on general considerations for clinical studies. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e8r1-general-considerations-clinical-studies
[4]
Turner JH. Theranostic outcomes in clinical practice of oncology: What, So What, Now What? What’s More. Cancer Biother Radiopharm 2019; 34(3): 135-40.
[http://dx.doi.org/10.1089/cbr.2019.29006.jht] [PMID: 30973278]
[5]
Ryll B. No other interest can take precedence - a patient’s perspective on oncology drug development. Nat Rev Clin Oncol 2019; 16(8): 461-2.
[http://dx.doi.org/10.1038/s41571-019-0230-4] [PMID: 31110270]
[6]
Lee SJC, Murphy CC, Geiger AM, Gerber DE, Cox JV, Nair R, et al. Conceptual model for accrual to cancer clinical trials. J Clin Oncol. 2019.Doi.org/10.1200/JCO.19.00101
[7]
Huang GD, Bull J, Johnston McKee K, Mahon E, Harper B, Roberts JN. Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative. Contemp Clin Trials 2018; 66: 74-9.
[http://dx.doi.org/10.1016/j.cct.2018.01.003] [PMID: 29330082]
[8]
Freedman RA, Ruddy KJ. Who are the patients in our clinical trials for cancer? J Clin Oncol 2019; 37(18): 1519-23.
[http://dx.doi.org/10.1200/JCO.19.00382] [PMID: 30995173]
[9]
May M. Twenty-five ways clinical trials have changed in the last 25 years. Nat Med 2019; 25(1): 2-5.
[http://dx.doi.org/10.1038/s41591-018-0314-1] [PMID: 30617334]
[10]
Sartor O, de Bono JS. Metastatic prostate cancer. N Engl J Med 2018; 378(7): 645-57.
[http://dx.doi.org/10.1056/NEJMra1701695] [PMID: 29412780]
[11]
Cherny NI, de Vries EGE, Dafni U, Garrett-Mayer E, McKernin SE, Piccart M, et al. Comparative assessment of clinical benefit using the ESMO-magnitude of clinical benefit scale version1.1 and the ASCO value framework net health benefit score. J Clin Oncol 2019; 37(4): 336-49.
[http://dx.doi.org/10.1200/JCO.18.00729] [PMID: 30707056]
[12]
Bachy E, Seymour JF, Feugier P, et al. Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: Long-term results of the PRIMA Study. J Clin Oncol 2019; 37(31): 2815-24.
[http://dx.doi.org/10.1200/JCO.19.01073] [PMID: 31339826]
[13]
Hall PS. Real-world data for efficient health technology assessment. Eur J Cancer 2017; 79: 235-7.
[http://dx.doi.org/10.1016/j.ejca.2017.04.003] [PMID: 28522211]
[14]
Morschhauser F, Fowler NH, Feugier P, et al. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med 2018; 379(10): 934-47.
[http://dx.doi.org/10.1056/NEJMoa1805104] [PMID: 30184451]
[15]
LeBlanc TW, Abernethy AP. Patient-reported outcomes in cancer care - hearing the patient voice at greater volume. Nat Rev Clin Oncol 2017; 14(12): 763-72.
[http://dx.doi.org/10.1038/nrclinonc.2017.153] [PMID: 28975931]
[16]
Gross CP, Gluck AR. Soaring cost of cancer treatment: Moving beyond sticker shock. J Clin Oncol 2018; 36(4): 305-7.
[http://dx.doi.org/10.1200/JCO.2017.76.0488] [PMID: 29236571]
[17]
Prasad V, McCabe C, Mailankody S. Low-value approvals and high prices might incentivize ineffective drug development. Nat Rev Clin Oncol 2018; 15(7): 399-400.
[http://dx.doi.org/10.1038/s41571-018-0030-2] [PMID: 29760505]
[18]
Ma CKK, Danta M, Day R, Ma DDF. Dealing with the spiralling price of medicines: issues and solutions. Intern Med J 2018; 48(1): 16-24.
[http://dx.doi.org/10.1111/imj.13652] [PMID: 29068529]
[19]
Ramsey SD, Shankaran V, Sullivan SD. Basket cases: How real-world testing for drugs approved based on basket trials might lead to false diagnoses, patient risks and squandered resources. J Clin Oncol 2019; 37(36): 3472-4.
[http://dx.doi.org/10.1200/JCO.18.02320] [PMID: 31233352]
[20]
Das M. Many FDA-approved cancer drugs might lack clinical benefit. Lancet Oncol 2018; 19(2)e82
[http://dx.doi.org/10.1016/S1470-2045(17)30954-3] [PMID: 29276024]
[21]
Uyl-de Groot CA. The promise of real-world data. Nat Med 2019. In press
[http://dx.doi.org/10.1038/d41591-019-00010-z]
[22]
Booth CM, Karim S, Mackillop WJ. Real-world data: towards achieving the achievable in cancer care. Nat Rev Clin Oncol 2019; 16(5): 312-25.
[http://dx.doi.org/10.1038/s41571-019-0167-7] [PMID: 30700859]
[23]
Davis B, Morgan J, Shah S. Getting real with real-world evidence 2017.Available at: www.deloitte.com/us/real-world-evidence.
[24]
Friends of Cancer Research. Establishing a framework to evaluate real-world endpoints 2018.www.focr.org/rwe
[25]
Statement from FDA commissioner Scott Gottlieb. Available at: www.fda.gov/New Events Newsroom/Press Announcements/ucm 627760.htm 2018
[26]
Soni PD, Hartman HE, Dess RT, et al. Comparison of population-based observational studies with randomized trials in oncology. J Clin Oncol 2019; 37(14): 1209-16.
[http://dx.doi.org/10.1200/JCO.18.01074] [PMID: 30897037]
[27]
Kulkarni HR, Singh A, Langbein T, et al. Theranostics of prostate cancer: from molecular imaging to precision molecular radiotherapy targeting the prostate specific membrane antigen. Br J Radiol 2018; 91(1091)20180308
[http://dx.doi.org/10.1259/bjr.20180308] [PMID: 29762048]
[28]
von Eyben FE, Roviello G, Kiljunen T, et al. Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. Eur J Nucl Med Mol Imaging 2018; 45(3): 496-508.
[http://dx.doi.org/10.1007/s00259-017-3895-x] [PMID: 29247284]
[29]
Westgeest HM, Uyl-de Groot CA, van Moorselaar RJA, et al. Differences in trial and real-world populations in the Dutch castration-resistant prostate cancer registry. Eur Urol Focus 2018; 4(5): 694-701.
[http://dx.doi.org/10.1016/j.euf.2016.09.008] [PMID: 28753794]
[30]
Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with castration-resistant prostate cancer (Lu-PSMA trial); a single-centre, single-arm, phase 2 study. Lancet Oncol 2018; 19: 835-3.
[http://dx.doi.org/10.1016/S1470-2045(18)30198-0]
[31]
Kratochwil C, Fendler WP, Eiber M, et al. EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging 2019; 46(12): 2536-44.
[http://dx.doi.org/10.1007/s00259-019-04485-3] [PMID: 31440799]
[32]
Yordanova A, Linden P, Hauser S, et al. Outcome and safety of rechallenge [177Lu]Lu-PSMA-617 in patients with metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2019; 46(5): 1073-80.
[http://dx.doi.org/10.1007/s00259-018-4222-x] [PMID: 30474706]
[33]
Kratochwil C, Bruchertseifer F, Rathke H, et al. Targeted alpha-therapy of metastatic castrate-resistant prostate cancer with 225Ac-PSMA-617: Swimmer plot analysis suggests efficacy regarding duration of tumor control. J Nucl Med 2018; 59(5): 795-802.
[http://dx.doi.org/10.2967/jnumed.117.203539] [PMID: 29326358]
[34]
Basch E, Deal AM, Kris MG, et al. Symptom monitoring with patient-reported outcomes during routine cancer treatment: A randomized controlled trial. J Clin Oncol 2016; 34(6): 557-65.
[http://dx.doi.org/10.1200/JCO.2015.63.0830] [PMID: 26644527]
[35]
Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes 2006; 4: 79.
[http://dx.doi.org/10.1186/1477-7525-4-79] [PMID: 17034633]
[36]
Basch E. Patient-reported outcomes-harnessing patient’s voices to improve clinical care. N Engl J Med 2017; 376(2): 105-8.
[http://dx.doi.org/10.1056/NEJMp1611252] [PMID: 28076708]
[37]
Thompson CA, Novotny PJ, Bartz A, Yost KJ. Development of a novel emoji scale to measure patient-reported outcomes in cancer patients. J Clin Oncol 2018; 36(7 suppl.)
[38]
Bertagnolli MM. ASCO Presidential Address: Caring for every patient, learning from every patient. J Clin Oncol 2019; 37(26): 2301-5.
[http://dx.doi.org/10.1200/JCO.19.01584] [PMID: 31343906]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 31
Year: 2020
Published on: 16 September, 2020
Page: [3799 - 3803]
Pages: 5
DOI: 10.2174/1381612826666200312141347
Price: $65

Article Metrics

PDF: 25
HTML: 4
PRC: 1