PMID- 34309669 OWN - NLM STAT- MEDLINE DCOM- 20220103 LR - 20220324 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 4 IP - 7 DP - 2021 Jul 1 TI - Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non-Small Cell Lung or Colorectal Cancer. PG - e2117547 LID - 10.1001/jamanetworkopen.2021.17547 [doi] LID - e2117547 AB - IMPORTANCE: Contemporary observational cancer research requires associating genomic biomarkers with reproducible end points; overall survival (OS) is a key end point, but interpretation can be challenging when multiple lines of therapy and prolonged survival are common. Progression-free survival (PFS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) are alternative end points, but their utility as surrogates for OS in real-world clinicogenomic data sets has not been well characterized. OBJECTIVE: To measure correlations between candidate surrogate end points and OS in a multi-institutional clinicogenomic data set. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted of patients with non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) whose tumors were genotyped at 4 academic centers from January 1, 2014, to December 31, 2017, and who initiated systemic therapy for advanced disease. Patients were followed up through August 31, 2020 (NSCLC), and October 31, 2020 (CRC). Statistical analyses were conducted on January 5, 2021. EXPOSURES: Candidate surrogate end points included TTD; TTNT; PFS based on imaging reports only; PFS based on medical oncologist ascertainment only; PFS based on either imaging or medical oncologist ascertainment, whichever came first; and PFS defined by a requirement that both imaging and medical oncologist ascertainment have indicated progression. MAIN OUTCOMES AND MEASURES: The primary outcome was the correlation between candidate surrogate end points and OS. RESULTS: There were 1161 patients with NSCLC (648 women [55.8%]; mean [SD] age, 63 [11] years) and 1150 with CRC (647 men [56.3%]; mean [SD] age, 54 [12] years) identified for analysis. Progression-free survival based on both imaging and medical oncologist documentation was most correlated with OS (NSCLC: rho = 0.76; 95% CI, 0.73-0.79; CRC: rho = 0.73; 95% CI, 0.69-0.75). Time to treatment discontinuation was least associated with OS (NSCLC: rho = 0.45; 95% CI, 0.40-0.50; CRC: rho = 0.13; 95% CI, 0.06-0.19). Time to next treatment was modestly associated with OS (NSCLC: rho = 0.60; 0.55-0.64; CRC: rho = 0.39; 95% CI, 0.32-0.46). CONCLUSIONS AND RELEVANCE: This cohort study suggests that PFS based on both a radiologist and a treating oncologist determining that a progression event has occurred was the surrogate end point most highly correlated with OS for analysis of observational clinicogenomic data. FAU - Kehl, Kenneth L AU - Kehl KL AD - Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. FAU - Riely, Gregory J AU - Riely GJ AD - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Lepisto, Eva M AU - Lepisto EM AD - Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. FAU - Lavery, Jessica A AU - Lavery JA AD - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Warner, Jeremy L AU - Warner JL AD - Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. AD - Department of Biomedical Informatics, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - LeNoue-Newton, Michele L AU - LeNoue-Newton ML AD - Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Sweeney, Shawn M AU - Sweeney SM AD - American Association for Cancer Research, Philadelphia, Pennsylvania. FAU - Rudolph, Julia E AU - Rudolph JE AD - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Brown, Samantha AU - Brown S AD - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Yu, Celeste AU - Yu C AD - Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre/University Health Network, Toronto, Ontario, Canada. FAU - Bedard, Philippe L AU - Bedard PL AD - Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre/University Health Network, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Schrag, Deborah AU - Schrag D AD - Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. AD - Associate Editor, JAMA. FAU - Panageas, Katherine S AU - Panageas KS AD - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. CN - American Association of Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) Consortium LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210701 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Biomarkers, Tumor) SB - IM CIN - JAMA Netw Open. 2021 Jul 1;4(7):e2117826. PMID: 34309673 MH - Aged MH - Biomarkers, Tumor/analysis MH - Carcinoma, Non-Small-Cell Lung/*mortality MH - Colorectal Neoplasms/*mortality MH - Female MH - Genomics/*methods MH - Genotype MH - Humans MH - Lung Neoplasms/*mortality MH - Male MH - Medical Oncology/*statistics & numerical data MH - Middle Aged MH - Progression-Free Survival MH - Radiology/statistics & numerical data MH - Retrospective Studies MH - Time-to-Treatment/statistics & numerical data MH - Withholding Treatment/statistics & numerical data PMC - PMC8314138 COIS- Conflict of Interest Disclosures: Dr Kehl reported receiving grants from Wong Family Foundation, American Association of Cancer Research (AACR), Simeon J. Fortin Foundation, Doris Duke Foundation, and the National Cancer Institute during the conduct of the study; grants from IBM; and personal fees from Aetion and Roche outside the submitted work. Dr Riely reported receiving grants from AACR during the conduct of the study; grants from Novartis, Pfizer, Merck, Mirati, Takeda, and Roche; and nonfinancial support from Pfizer and Merck outside the submitted work. Ms Lepisto reported receiving grants from AACR during the conduct of the study. Ms Lavery reported receiving grants from AACR during the conduct of the study. Dr Warner reported receiving grants from AACR during the conduct of the study; grants from the National Institutes of Health; consulting fees from Westat and IBM; and having equity in HemOnc.org LLC. Dr LeNoue-Newton reported receiving research funding from AACR during the conduct of the study; and research funding from GE Healthcare outside the submitted work. Dr Sweeney reported receiving grants from Amgen Inc, AstraZeneca UK Ltd, Bristol Myers Squibb, Bayer Healthcare Pharmaceuticals Inc, Boehringer Ingelheim, Genentech, Janssen Pharmaceuticals Inc, Merck Sharp & Dohme Corp, Novartis, and Pfizer Inc during the conduct of the study. Ms Brown reported receivng grants from AACR during the conduct of the study. Dr Bedard reported receiving grants from AACR during the conduct of the study; consulting fees from Seattle Genetics, Eli Lilly and Co, Amgen Inc, Merck Sharp & Dohme Corp, Bristol Myers Squibb, Sanofi, and Pizer; serving on the advisory boards for Bristol Myers Squibb, Eli Lilly and Co, Amgen, Seattle Genetics, Merck, Pfizer, and Gilead; and receiving research funding directed to his institution from Bristol Myers Squibb, Sanofi, AstraZeneca, Genentech, Servier, GlaxoSmithKline, Novartis, SignalChem, PTC Therapeutics, Nektar, Merck Sharp & Dohme Corp, Seattle Genetics, Mersana, Immunomedics, and Eli Lilly and Co. Dr Schrag reported receiving fees from JAMA for editorial services; speaking fees from Pfizer; research funding given directly to the institution from AACR, Patient-Centered Outcomes Research Institute, GRAIL, and the National Cancer Institute (NCI). Dr Panageas reported receiving grants from NCI Cancer Center Support Grant and research funding from AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) Consortium during the conduct of the study. AACR Project GENIE receives funding from Amgen Inc, Bristol Myers Squibb Co, Merck Sharp & Dohme Corp, AstraZeneca UK Ltd, Genentech, Novartis, Bayer Healthcare Pharmaceuticals Inc, H3 Biomedicine, Puma Biotechnology, Boehringer Ingelheim, and Janssen Pharmaceuticals Inc. No other disclosures were reported. 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Aguilar Izquierdo, Susana IR - Aguilar Izquierdo S FIR - Viaplana Donato, Cristina IR - Viaplana Donato C FIR - Mancuso, Francesco IR - Mancuso F FIR - Topaloglu, Umit IR - Topaloglu U FIR - Liu, Liang IR - Liu L FIR - Guan, Meijian IR - Guan M FIR - Zhang, Wei IR - Zhang W FIR - Jin, Guangxu IR - Jin G FIR - Knight, James IR - Knight J FIR - D'Eletto, Michael IR - D'Eletto M FIR - Ormay, E Zeynep IR - Ormay EZ FIR - Mane, Shrikant IR - Mane S FIR - Bilguvar, Kaya IR - Bilguvar K FIR - Zenta, Walther IR - Zenta W FIR - Dykas, Daniel IR - Dykas D EDAT- 2021/07/27 06:00 MHDA- 2022/01/04 06:00 PMCR- 2021/07/26 CRDT- 2021/07/26 12:28 PHST- 2021/07/26 12:28 [entrez] PHST- 2021/07/27 06:00 [pubmed] PHST- 2022/01/04 06:00 [medline] PHST- 2021/07/26 00:00 [pmc-release] AID - 2782339 [pii] AID - zoi210522 [pii] AID - 10.1001/jamanetworkopen.2021.17547 [doi] PST - epublish SO - JAMA Netw Open. 2021 Jul 1;4(7):e2117547. doi: 10.1001/jamanetworkopen.2021.17547.