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Results of the first experimental group using véliparib as part of total neoadjuvant therapy (induction chemotherapy followed by chemoradiotherapy and surgery; TNT) in patients with locally advanced rectal adenocarcinoma in the Phase II clinical trial NRG-Oncology NRG-GI002 recently presented at the American Society of Clinical Oncology (ASCO). Results were reported on the primary endpoint of pathological regression via the neoadjuvant rectal cancer score (NAR), a short-term proxy for the clinical trial.
After treatment with a combination of chemotherapy called mFOLFOX6, the researchers badociated with véliparib, an inhibitor of poly (ADP-ribose) polymerase (PARP) or a drug that kills cancer cells by blocking a protein called PARP, with another chemotherapeutic agent called capecitabine, and radiotherapy. patients with locally advanced stages 2 or 3. Patients in the control group received the same treatment, with the absence of véliparib. In the first experimental group of NRG-GI002, veliparib has been added to radiotherapy and chemotherapy regimens, as PARP inhibitors, such as veliparib, have been shown to enhance the efficacy of radiotherapy in patients with radiotherapy. interfering with the patient's DNA repair mechanisms and thereby destroying tumor cells. or the amount of normal tissue to remove. The results of the global study demonstrate that the TNT approach to therapy is safe and badociated with high (> 90%) completion rates of chemotherapy. However, the addition of véliparib did not significantly improve the reduction in the number of cancers present at the time of surgery. The primary endpoint of the mean rectal neoadjuvant score (NAR) (the lowest figure reflecting further downstaging) was 12.6 for the control arm and 13.7 for the experimental arm (p = 0, 69). The number of patients who achieved pCR with véliparib was numerically higher (22% vs 34%, p = 0.14). Early experimental results showed that the addition of véliparib was badociated with more short-term side effects and reduced completion of chemoradiotherapy (85% vs. 70%, p = 0.026). The most common grade 3 and 4 adverse events observed in the first experimental arm of NRG-GI002 included diarrhea and cytopenias. Importantly, these side effects did not appear to have a negative impact on the short-term outcome of patients.
"NRG-GI002 is intended to serve as a platform for testing new agents, such as veliparib, or other novel hypotheses using total neoadjuvant therapy for rectal cancer under a flat Phase II clinical trial format, "said Thomas J. George, MD, FACP, of the University of Florida's Center for Cancer Cancer Health and senior author of the NRG-GI002 summary. "The objective of this study was to build on the encouraging results obtained with véliparib in the Phase I trial, which produced few dose-limiting toxicities." Our randomized phase II trial combined véliparib with 400 mg PO IDB with chemotherapy followed by surgery to observe improvement in patients'. A NAR score that would result in an improvement in overall survival and the absence of disease. 39, we have not seen any improvement with the use of véliparib.However, and it is very important, we have now established that TNT can be administered safely and successfully to patients with Rectal administration locally advanced cancer.This ensures that all patients receive the treatments they need and gives us many opportunities to further improve care for this group of patients. e patients. "
The future direction of this trial includes ongoing badysis of secondary endpoints and biomarkers to determine which specific patients have benefited from the addition of véliparib and why. A second ongoing experimental group observes the impact of monoclonal antibody pembrolizumab in combination with capecitabine and radiotherapy after induction of mFOLFOX6 to determine whether immunotherapy is also a safe and effective option for the treatment of cancer. Locally advanced rectum. This second branch has completed its registration with the expected results. Additional arms are being actively developed with the goal of improving outcomes for patients with this disease.
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This study was funded by grants U10CA180868, U10CA180822, UG1CA189867 and U24CA196067, as well as AbbVie's drug badistance. Additional support was provided by the NCI Biomarker, Imaging and Quality of Life Studies Funding Program (BIQSFP).
Quote
George TJ, Yothers G, TS Hong, MM Russell, You YN, Parker W, Jacobs SA, Lucas PC, Gollub MJ, WA Hall, Kachnic LA, Vijayvergia N, Wolmark N. NRG-GI002: a testing platform phase II clinical trials using Total Neoadjuvant Therapy (TNT) in Locally Advanced Rectal Cancer (LARC): First Results of the Experimental Arm (EA). Abstract presented at the annual meeting of the American Society of Clinical Oncology (ASCO). Chicago, IL.
Aabout NRG Oncology
NRG Oncology conducts multi-institutional clinical and translational research that changes practices to improve the lives of cancer patients. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit company that integrates research from the National Project on Breast and Surgical Adjuvant Adjuvants (NSABP), the Radiation Oncology Group (RTOG) and the Group. of Gynecologic Oncology (GOG). The research network seeks to conduct clinical trials with a focus on badual malignancies, including gynecological, bad and prostate cancers, as well as all types of localized or locally advanced cancers. NRG Oncology's extensive research organization includes multidisciplinary researchers, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists and statisticians. It has more than 1,300 research sites around the world, with a predominance in the United States and Canada. NRG Oncology is primarily funded by grants from the National Cancer Institute (NCI) and is one of five research groups in NCI's National Clinical Trials Network.
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