Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non–Small Cell Lung or Colorectal Cancer
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. Bédard, Deborah Schrag, Katherine S. Panageas, Shawn M. Sweeney, Margaret Foti, Yekaterina B. Khotskaya, Michael V. Fiandalo, Benjamin E. Gross, Nikolaus Schultz, Brooke Mastrogiacomo, Mahdi Sarmardy, Marilyn M. Li, Adam Resnick, Angela J. Waanders, Jena Lilly, Richard D. Carvajal, Raúl Rabadán, Matthew Ingham, Susan Hsaio, Jean Abraham, James D. Brenton, Oscar M. Rueda, Carlos Caldas, Mikel Valgañón, Dilrini De Silva, Chris Boursnell, Raquel Rodríguez-García, E. Vargaz Rodriguez, Birgit Nimmervoll, Ethan Cerami, Matthew D. Ducar, Priti Kumari, Neal I. Lindeman, Laura MacConnaill, John A. Orechia, Deborah Schrag, Priyanka Shivdasani, Eliezer M. Van Allen, Jason M. Johnson, Pasi A. Jänne, Eva M. Lepisto, Michael J. Hassett, Sindy Pimentel, Parin Sripakdeevong, Katherine A. Janeway, Jason M. Johnson, Matthew Meyerson, Daniel M. Quinn, Oya Cushing, Kevin M. Haigis, Diana Miller, Kenneth L. Kehl, Alexander Gustav, Angela C. Tramontano, Simon Arango Baquero, Jonathan L. Bell, Michelle Green, Shannon J. McCall, Michael Datto, Fabien Calvo, Fabrice André, Meurice Guillaume, Semih Doğan, Lacroix Ludovic, Jean Scoazec, Monica Ardenos, Gilles Vassal, Stefan Michels, Victor E. Velculescu, Alexander S. Baras, Christopher D. Gocke, Julie R. Brahmer, Charles L. Sawyers, David B. Solit, Stuart M. Gardos, Mike Berger, Marc Ladanyi, Gregory J. Riely, S. Joseph Sirintrapun, Ari Caroline, Stacy B. Thomas, Andrew Zarski, Ahmet Zehir, Alexia Iasonosa, John Philip, Samantha Brown, Andrew L. Kung, Ritika Kundra, Julia E. Rudolph, Jessica A. Lavery
Abstract
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: 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). 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.