TY - JOUR
T1 - Eligibility and Radiologic Assessment for Adjuvant Clinical Trials in Kidney Cancer
AU - Agrawal, Sundeep
AU - Haas, Naomi B.
AU - Bagheri, Mohammadhadi
AU - Lane, Brian R.
AU - Coleman, Jonathan
AU - Hammers, Hans
AU - Bratslavsky, Gennady
AU - Chauhan, Cynthia
AU - Kim, Lauren
AU - Krishnasamy, Venkatesh P.
AU - Marko, Jamie
AU - Maher, Virginia Ellen
AU - Ibrahim, Amna
AU - Cross, Frank
AU - Liu, Ke
AU - Beaver, Julia A.
AU - Pazdur, Richard
AU - Blumenthal, Gideon M.
AU - Singh, Harpreet
AU - Plimack, Elizabeth R.
AU - Choueiri, Toni K.
AU - Uzzo, Robert
AU - Apolo, Andrea B.
N1 - Funding Information:
reported receiving grants, personal fees, and travel expenses from Bristol Myers-Squibb; personal fees and travel expenses from Merck; personal fees from Eli Lilly and Co, Exelixis, Pfizer, Novartis, and Armo Biosciences outside the submitted work. Dr Maher reported currently working at DataRevive and being employed by the Food and Drug Administration during preparation of this manuscript. Dr Plimack reported receiving personal fees from Acceleron, AstraZeneca, Bristol-Myers Squibb, Clovis, Dendreon, Exelexis, Genentech/Roche, Horizon Pharma, Inovio, Merck, Novartis, Pfizer, Synergene, Eli Lilly and Co; receiving grants from Acceleron, Aveo, Bristol-Myers Squibb, Eli Lilly and Co, Merck, Peloton, and Pfizer outside the submitted work; conducting institutional and personal research for Analysis Group, AstraZeneca, Alexion, Bayer, Bristol Myers-Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Eli Lilly and Co, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Sanofi, and Takeda; receiving honoraria from Analysis Group, AstraZeneca, Alexion, Sanofi, Bayer, Bristol Myers-Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Heron Therapeutics, Eli Lilly and Co, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, National Comprehensive Cancer Network (NCCN), Analysis Group, Michael J. Hennessy Associates Inc, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, New England Journal of Medicine, and Lancet Oncology; filling a consulting or advisory role for Analysis Group, AstraZeneca, Alexion, Sanofi, Bayer, Bristol Myers-Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Genentech, Heron Therapeutics, Eli Lilly and Co, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, and NCCN; serving in leadership or membership roles at Dana-Farber Cancer Institute, NCCN Kidney Panel, GU Steering Committee, Kidney Cancer Association Medical and Scientific Steering Committee; holding International Patent Application No. PCT/US2018/12209 (PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response, filed January 3, 2018; claiming priority to US Provisional Patent Application No. 62/445,094, filed January 11, 2017) and International Patent Application No. PCT/US2018/058430 (Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy, filed October 31, 2018; claiming priority to US Provisional Patent Application No. 62/581,175, filed November 3, 2017); and receiving medical writing and editorial assistance support from communications companies funded by pharmaceutical companies. Dr Choueiri reported receiving research support (institutional and personal) from AstraZeneca, Alexion, Bayer, Bristol Myers-Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Eli Lilly and Co, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Sanofi, Takeda, the National Cancer Institute, the National Institutes of Health, and the Department of Defense; honoraria from AstraZeneca, Alexion, Sanofi, Bayer, Bristol Myers-Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, Michael J. Hennessy Associates Inc, Research to Practice, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, New England Journal of Medicine, Lancet Oncology, Heron Therapeutics, Eli Lilly and Co, the American Society of Clinical Oncology, and the European Society for Medical Oncology; consulting or advisory compensation for AstraZeneca, Alexion, Sanofi, Bayer, Bristol Myers-Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Heron Therapeutics, Eli Lilly and Co, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, Pionyr, and Tempest; stock ownership in Pionyr and Tempest; present or past leadership roles including Director of GU Oncology Division at Dana-Farber Cancer Institute and past president of medical staff at Dana-Farber Cancer Institute, member of NCCN Kidney panel and the GU Steering Committee, and past chairman of the Kidney Cancer Association Medical and Scientific Steering Committee; holding International Patent Application No. PCT/US2018/ 12209 (PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response), filed January 3, 2018, claiming priority to US Provisional Patent Application No. 62/445,094, filed January 11, 2017, and International Patent Application No. PCT/ US2018/058430 (Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy), filed October 31, 2018, claiming priority to US Provisional Patent Application No. 62/581,175, filed November 3, 2017; and mentoring several non-US citizens on research projects with potential funding (in part) from non-US sources or foreign components outside the submitted work. Dr Uzzo reported receiving personal fees from Pfizer, funding for investigator-initiated trials from Novartis and Genentech, and personal fees from Janssen outside the submitted work. No other disclosures were reported.
Funding Information:
Funding/Support: This study was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2020/1
Y1 - 2020/1
N2 - Purpose: To harmonize the eligibility criteria and radiologic disease assessment definitions in clinical trials of adjuvant therapy for renal cell carcinoma (RCC). Method: On November 28, 2017, US-based experts in RCC clinical trials, including medical oncologists, urologic oncologists, regulators, biostatisticians, radiologists, and patient advocates, convened at a public workshop to discuss eligibility for trial entry and radiologic criteria for assessing disease recurrence in adjuvant trials in RCC. Multiple virtual meetings were conducted to address the issues identified at the workshop. Results: The key workshop conclusions for adjuvant RCC therapy clinical trials were as follows. First, patients with non-clear cell RCC could be routinely included, preferably in an independent cohort. Second, patients with T3-4, N+M0, and microscopic R1 RCC tumors may gain the greatest advantages from adjuvant therapy. Third, trials of agents not excreted by the kidney should not exclude patients with severe renal insufficiency. Fourth, therapy can begin 4 to 16 weeks after the surgical procedure. Fifth, patients undergoing radical or partial nephrectomy should be equally eligible. Sixth, patients with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials. Seventh, all suspicious regional lymph nodes should be fully resected. Eighth, computed tomography should be performed within 4 weeks before trial enrollment; for patients with renal insufficiency who cannot undergo computed tomography with contrast, noncontrast chest computed tomography and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be performed. Ninth, when feasible, biopsy should be undertaken to identify any malignant disease. Tenth, when biopsy is not feasible, a uniform approach should be used to evaluate indeterminate radiologic findings to identify what constitutes no evidence of disease at trial entry and what constitutes radiologic evidence of disease. Eleventh, a uniform approach for establishing the date of recurrence should be included in any trial design. Twelfth, patient perspectives on the use of placebo, conditions for unblinding, and research biopsies should be considered carefully during the conduct of an adjuvant trial. Conclusions and Relevance: The discussions suggested that a uniform approach to eligibility criteria and radiologic disease assessment will lead to more consistently interpretable trial results in the adjuvant RCC therapy setting.
AB - Purpose: To harmonize the eligibility criteria and radiologic disease assessment definitions in clinical trials of adjuvant therapy for renal cell carcinoma (RCC). Method: On November 28, 2017, US-based experts in RCC clinical trials, including medical oncologists, urologic oncologists, regulators, biostatisticians, radiologists, and patient advocates, convened at a public workshop to discuss eligibility for trial entry and radiologic criteria for assessing disease recurrence in adjuvant trials in RCC. Multiple virtual meetings were conducted to address the issues identified at the workshop. Results: The key workshop conclusions for adjuvant RCC therapy clinical trials were as follows. First, patients with non-clear cell RCC could be routinely included, preferably in an independent cohort. Second, patients with T3-4, N+M0, and microscopic R1 RCC tumors may gain the greatest advantages from adjuvant therapy. Third, trials of agents not excreted by the kidney should not exclude patients with severe renal insufficiency. Fourth, therapy can begin 4 to 16 weeks after the surgical procedure. Fifth, patients undergoing radical or partial nephrectomy should be equally eligible. Sixth, patients with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials. Seventh, all suspicious regional lymph nodes should be fully resected. Eighth, computed tomography should be performed within 4 weeks before trial enrollment; for patients with renal insufficiency who cannot undergo computed tomography with contrast, noncontrast chest computed tomography and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be performed. Ninth, when feasible, biopsy should be undertaken to identify any malignant disease. Tenth, when biopsy is not feasible, a uniform approach should be used to evaluate indeterminate radiologic findings to identify what constitutes no evidence of disease at trial entry and what constitutes radiologic evidence of disease. Eleventh, a uniform approach for establishing the date of recurrence should be included in any trial design. Twelfth, patient perspectives on the use of placebo, conditions for unblinding, and research biopsies should be considered carefully during the conduct of an adjuvant trial. Conclusions and Relevance: The discussions suggested that a uniform approach to eligibility criteria and radiologic disease assessment will lead to more consistently interpretable trial results in the adjuvant RCC therapy setting.
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U2 - 10.1001/jamaoncol.2019.4117
DO - 10.1001/jamaoncol.2019.4117
M3 - Review article
C2 - 31750870
AN - SCOPUS:85075657286
SN - 2374-2437
VL - 6
SP - 133
EP - 141
JO - JAMA Oncology
JF - JAMA Oncology
IS - 1
ER -