Impact of postprogression therapies on overall survival: Recommendations from the 2023 kidney cancer association think tank meeting
Year: 2024
Type: article
Abstract: Modern advances in systemic and localized therapies for patients with renal cell carcinoma (RCC) have significantly improved patients' outcomes. If disease progression occurs after initial treatment, clinicians often have multiple options for a first salvage therapy. Because salvage and initial treatments both may affect overall survival time, and they may interact in unanticipated ways, there is a growing need to determine sequences of initial therapy and first salvage therapy that maximize overall survival while maintaining quality of life. The complexity of this problem grows if a second salvage therapy must be chosen for patients with treatment-resistant disease or a second progression occurs following first salvage. On November 9, 2023, a think tank was convened during the International Kidney Cancer Symposium (IKCS) North America to discuss challenges in accounting for postprogression therapies when estimating overall survival (OS) time based on randomized controlled trial (RCT) data. The present manuscript summarizes the topics discussed, with the aim to encourage adoption of statistical methods that account for salvage therapy effects to obtain scientifically valid OS estimation. We highlight limitations of traditional methods for estimating OS that account for initial treatments while ignoring salvage therapy effects and discuss advantages of applying more sophisticated statistical methods for estimation and trial design. These include identifying multistage treatment strategies, correcting for confounding due to salvage therapy effects, and conducting Sequentially Multiple Assignment Randomized Trials (SMARTs) to obtain unbiased comparisons between multistage strategies. We emphasize the critical role of patient input in trial design, and the potential for information technology (IT) advances to support complex trial designs and real-time data analyses. By addressing these challenges, future RCTs can better inform clinical decision-making and improve patient outcomes in RCC.
Authors: Stephanie A. Berg, Salvatore La Rosa, Tian Zhang, Phillip M. Pierorazio, Laurence Albiges, Kathryn E. Beckermann, Matthew T. Campbell, Maria I. Carlo, Katie Coleman, Daniel J. George, Daniel M. Geynisman, Ritchie Johnson, Eric Jonasch, Jodi K. Maranchie, Bradley A. McGregor, Daniel D. Shapiro, Eric A. Singer, Brian M. Shuch, Walter M. Stadler, Nizar M. Tannir, Yousef Zakharia, Ulka N. Vaishampayan, Peter F. Thall, Pavlos Msaouel
Institutions: Harvard University, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Kidney Cancer Association, The University of Texas Southwestern Medical Center, University of Pennsylvania, Institut Gustave Roussy, Vanderbilt University Medical Center, The University of Texas MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, Duke University, Duke Cancer Institute, Fox Chase Cancer Center, University of Pittsburgh, University of Wisconsin–Madison, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, University of California, Los Angeles, University of Chicago, University of Iowa Hospitals and Clinics, University of Michigan
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,340
OpenAlex ID: W4404086900