RTOG 3508 Interim Analysis Yields no Survival Benefit with the Addition of Depatuxizumab-Mafodotin for EGRF-amplified Newly Diagnosed Glioblastoma

September 13, 2022

Results from the Phase III RTOG Foundation RTOG 3508 clinical trial, sponsored by AbbVie, which added the antibody drug conjugate depatuxizumab-mafodotin (depatux-m) to the standard treatment for patients with EGRF-amplified newly diagnosed glioblastomas (GBMs) indicated that the addition of depatux-m lead to no improvement or benefit for overall survival outcomes in this patient population. No new important safety risks were found with the use of depatux-m for trial participants. RTOG 3508 is among the first late-stage studies of an EGFR-directed antibody drug conjugate for glioblastoma. Data from this trial is published in Neuro-Oncology. 

RTOG 3508 accrued 639 patients with centrally confirmed, EGFR-amplified, newly diagnosed GBM and randomly assigned patients to receive the standard of care radiotherapy and temozolomide with either depatux-m or with a placebo. 

Although RTOG 3508 demonstrated no overall survival benefit for GBM patients, longer progression-free survival was observed in patients on the study who received depatux-m compared to placebo. 

“Glioblastomas are one of the most common and aggressive primary brain tumors in adults, and over half of these newly-diagnosed GBM patients harbor EGFR gene amplification. The prevalence and aggressiveness of this disease emphasize the urgent need for continued randomized, late phase trials in this space in an effort to find treatment options that improve survival outcomes for these patients,” stated Andrew B. Lassman, MD, of the New York Presbyterian Hospital, the Columbia University Irving Medical Center, the Herbert Irving Comprehensive Cancer Center, and the lead author of the RTOG 3508 manuscript. 

RTOG 3508 had 85% power to detect a Hazard Ratio (HR), 0.75 for overall survival  at a 2.5% one-sided significance level by log-rank testing. There was no improvement in overall survival for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95% CI 0.82-1.26, one-sided p=0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95% CI 0.70-1.01, p=0.029), particularly among those with EGFRvIII mutant (median 8.3 vs. 5.9 months, HR 0.72, 95% CI 0.56-0.93, p=0.002 one sided) or MGMT unmethylated (HR 0.77, 95% CI 0.61-0.97; p=0.012 one-sided) tumors but without an OS improvement. Corneal epitheliopathy occurred in 94% of depatux-m treated patients (61% grade 3-4), causing 12% to discontinue. 

Continued research is underway to follow up on these findings and expand upon them in clinical design and ancillary project settings.  

 

Citation
Lassman AB, Pugh SL, Wang TJC, Aldape K, Gan HK, Preusser M, Vogelbaum MA, Sulman EP, Won M, Zhang P, Moazami G, Macsai MS, Gilbert MR, Bain EE, Blot V, Ansell PJ, Samanta S, Kundu MG, Armstrong TS, Wefel JS, Seidel C, de Vos FY, Hsu S, Cardona AF, Lombardi G, Bentsion D, Peterson RA, Gedye C, Bourg V, Wick A, Curran WJ, Mehta MP. Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial. Neuro Oncol. 2022 Jul 15:noac173. doi: 10.1093/neuonc/noac173. Epub ahead of print. PMID: 35849035.

 

About RTOG Foundation
The RTOG Foundation is a nonprofit organization dedicated to improving outcomes for cancer patients through the conduct of practice changing clinical trials. RTOGF collaborates with partners from industry and federally funded programs to support its research. RTOGF is the successor of the National Cancer Institute(NCI)-funded Radiation Therapy Oncology group that was organized in 1968 as a national clinical cooperative group for the purpose of conducting multicenter radiation therapy research and clinical investigations. It was part of the NCI-funded cooperative group program and managed by the American College of Radiology (ACR) from 1971 until 2014. During that time, it activated over 500 protocols, accrued more than 110,000 patients to cooperative group studies, and published over 1,000 papers reporting the results of its findings. RTOGF has continued its close relationship with ACR to engage in clinical trial research collaborations with a variety of industry partners and participates in Federal grant-funded research through its leadership in the NCI National Clinical Trial Network group NRG Oncology.