Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non–Small Cell Lung or Colorectal Cancer
Authors: Kenneth L. Kehl, Gregory J. Riely, Eva M. Lepisto, Jessica A. Lavery, Jeremy L. Warner, Michele L. LeNoue-Newton, Shawn M. Sweeney, Julia E. Rudolph, Samantha Brown, Celeste Yu, Philippe L. Bedard, Deborah Schrag, Katherine S. Panageas, Shawn Sweeney, Margaret Foti, Yekaterina Khotskaya, Michael Fiandalo, Benjamin Gross, Nikolaus Schultz, Brooke Mastrogiacomo, Mahdi Sarmardy, Marilyn Li, Adam Resnick, Angela Waanders, Jena Lilly, Richard Carvajal, Raul Rabadan, Matthew Ingham, Susan Hsaio, Jean Abraham, James Brenton, Oscar Rueda, Carlos Caldas, Mikel Valgañón, Dilrini Silva, Chris Boursnell, Raquel Garcia, Ezequiel Rodriguez, Birgit Nimmervoll, Ethan Cerami, Matthew Ducar, Priti Kumari, Neal Lindeman, Laura MacConnaill, John Orechia, Deborah Schrag, Priyanka Shivdasani, Eliezer Van Allen, Jason Johnson, Pasi Jänne, Eva Lepisto, Michael Hassett, Sindy Pimentel, Parin Sripakdeevong, Katherine Janeway, Jason M. Johnson, Matthew Meyerson, Daniel Quinn, Oya Cushing, Kevin Haigis, Diana Miller, Kenneth Kehl, Alexander Gustav, Angela Tramontano, Simon Arango Baquero, Jonathan Bell, Michelle Green, Shannon McCall, Michael Datto, Fabien Calvo, Fabrice Andre, Meurice Guillaume, Semih Dogan, Lacroix Ludovic, Jean Scoazec, Monica Ardenos, Gilles Vassal, Stefan Michels, Victor Velculescu, Alexander Baras, Christopher Gocke, Julie Brahmer, Charles Sawyers, David Solit, Stu Gardos, Mike Berger, Marc Ladanyi, Gregory Riely, Joseph Sirintrapun, Ari Caroline, Stacy Thomas, Andrew Zarski, Ahmet Zehir, Alexia Iasonosa, John Philip, Samantha Brown, Andrew Kung, Ritika Kundra, Julia Rudolph, Jessica Lavery, Hira Rivzi, Julian Schwartz, Caroline McCarthy, Maufur Bhuiya, Axel Martin, Cynthia Chu, Raymond DuBois, Tony van de Velde, Geritt Meijer, Hugo Horlings, Harm van Tinteren, Martijn Lolkema, Les Nijman, Mariska Bierkens, Jelle Hoeve, Emilie Voest, Annemieke Hiemstra, Gabe Sonke, Jacques Craenmehr, Jan Hudecek, Kim Monkhorst, Walter Urba, Brady Bernard, Brian Piening, Carlo Bifulco, Paul Tittel, Julie Cramer, Justin Guinney, Thomas Yu, Xindi Guo, Alyssa Acebedo, Philip Gold, Neil Bailey, Sabah Kadri, Jeremy Segal, Wanjari Pankhuri, Peng Wang, Steinhardt George, Moung Christine, Laura Van't Veer, Eric Talevich, Amanda Wren, Alejandro Sweet-Cordero, Michelle Turski, Philippe Bedard, Suzanne KamelReid, Zhibin Lu, Trevor Pugh, Lillian Siu, Stuart Watt, Natasha Leighl, Celeste Yu, Lailah Ahmed, Geeta Krishna, Carlos Virtaenen, Helen Chow, Demi Plagianakos, Samantha Del Rossi, Nitthusha Singaravelan, Sevan Hakgor, Nazish Qazi, Alisha Nguyen, Natalie Stickle, Thomas Stricker, Christine Micheel, Ingrid Anderson, Leigh Jones, Lucy Wang, Christine Lovly, Michele LeNoue Newton, Ben Park, Jeremy Warner, Daniel Fabbri, Joseph Coco, Chen Ye, Sandip Chaugai, Sanjay Mishra, Yuanchu James Yang, Li Wen, Rodrigo Dienstmann, Susana Aguilar Izquierdo, Cristina Viaplana Donato, Francesco Mancuso, Umit Topaloglu, Liang Liu, Meijian Guan, Wei Zhang, Guangxu Jin, James Knight, Michael D'Eletto, E. Zeynep Ormay, Shrikant Mane, Kaya Bilguvar, Walther Zenta, Daniel Dykas
Journal: JAMA Network Open (2021)

<h3>Importance</h3> 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. <h3>Objective</h3> To measure correlations between candidate surrogate end points and OS in a multi-institutional clinicogenomic data set. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> 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. <h3>Main Outcomes and Measures</h3> The primary outcome was the correlation between candidate surrogate end points and OS. <h3>Results</h3> 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: ρ = 0.76; 95% CI, 0.73-0.79; CRC: ρ = 0.73; 95% CI, 0.69-0.75). Time to treatment discontinuation was least associated with OS (NSCLC: ρ = 0.45; 95% CI, 0.40-0.50; CRC: ρ = 0.13; 95% CI, 0.06-0.19). Time to next treatment was modestly associated with OS (NSCLC: ρ = 0.60; 0.55-0.64; CRC: ρ = 0.39; 95% CI, 0.32-0.46). <h3>Conclusions and Relevance</h3> 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.