Ctni-17. Application of the Gbm-x Data Platform to Estimate Treatment Effects of the Experimental Therapies of the Randomized Phase 2 Individualized Screening Trial of Innovative Glioblastoma Therapies
Year: 2023
Type: article
Abstract: BACKGROUND Leveraging external data has the potential to increase efficiency and precision of drug development in glioblastoma by complementing or replacing data from in-trial controls. We used an external control arm (ECA) to re-analyze data of the abemaciclib, neratinib and CC-115 arms of the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. METHODS INSIGhT (NCT02977780) is an ongoing phase 2 adaptive platform trial in newly diagnosed MGMT unmethylated glioblastoma with a shared control arm of patients receiving radiation therapy with concurrent and maintenance temozolomide. The initial experimental arms (abemaciclib, neratinib, CC-115) have not shown a survival benefit relative to the shared control arm. We re-analyzed the experimental arm data and replaced the shared control arm with an ECA. The ECA was developed from a collection of trial datasets and real-world data available through the Glioblastoma External (GBM-X) Data Platform (). Propensity score matching was used to adjust for possible differences between pretreatment covariates (age, sex, resection, KPS) in the ECA and shared control arm. Cox proportional hazards models were used to estimate treatment effects. RESULTS On INSIGhT, patients were randomized to abemaciclib (n = 74), neratinib (n = 80), and CC-115 (n = 12). There were 687 unmethylated MGMT patients in the GBM-X ECA. After propensity score matching, there was no significant treatment effect associated with abemaciclib (HR 1.091, 95%CI:0.834-1.433, p = 0.536), neratinib (HR = 1.043, 95%CI:0.787-1.383, p = 0.770), or CC-115 (HR 1.088, 95%CI:0.834-1.433, p = 0.794) compared to the ECA. CONCLUSION In comparison to an ECA, there was no significant survival benefit with abemaciclib, neratinib and CC-115. Treatment effects estimates were similar to the primary analyses based on the original shared control arm of INSIGhT. The use of external control arms in early phase testing of new therapies is supported by our findings and could significantly reduce costs and time to conduct trials in newly diagnosed glioblastoma.
Source: Neuro-Oncology
Authors: Rifaquat Rahman, Lorenzo Trippa, Geoffrey Fell, Eudocia Lee, Isabel Arrillaga-Romany, Mehdi Touat, Jan Drappatz, Mary Welch, Evanthia Galanis, Manmeet Ahluwalia, Howard Colman, Burt Nabors, Jaroslaw Hepel, Heinrich Elinzano, David Schiff, Ugonma Chukwueke, Rameen Beroukhim, Lakshmi Nayak, Jose Ricardo McFaline-Figueroa, Tracy Batchelor, Mikael Rinne, Thomas Kaley, Christine Lu-Emerson, Ingo Mellinghoff, Wenya Linda Bi, Omar Arnaout, Pier Paolo Peruzzi, Daphne Haas-Kogan, Shyam Tanguturi, Daniel Cagney, Ayal Aizer, Lisa Doherty, Sandro Santagata, David Meredith, E Antonio Chiocca, David Reardon, Brian Alexander, Keith Ligon, Patrick Wen
Institutions: Dana-Farber Brigham Cancer Center, Dana-Farber Cancer Institute, Massachusetts General Hospital, Pitié-Salpêtrière Hospital, University of Pittsburgh Medical Center, Columbia University Irving Medical Center, Mayo Clinic, Baptist Hospital of Miami, Baptist Health South Florida, University of Utah, Huntsman Cancer Institute, University of Alabama at Birmingham, Rhode Island Hospital, University of Virginia, Center for Neuro-Oncology, Memorial Sloan Kettering Cancer Center, Maine Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Harvard University, Foundation Medicine (United States)
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4388589286