September 29 2019
NRG Oncology and the National Cancer Research Network (NCRN) collaborated on a phase II/III clinical trial NRG-GOG 0281 which compared treatment using the MEK inhibitor trametinib to the physician’s choice of standard of care treatment for women with low-grade serous ovary or peritoneal cancer (LGSOC). Results of this trial indicate that trametinib was able to improve progression-free survival (PFS) and objective response rate (ORR). Improvements in response duration and overall survival (OS) were also observed. These results were presented at the 2019 European Society for Medical Oncology Congress in September 2019.
“LGSOC is a rare subtype that accounts for 5-10% of all serous cancers; however, most women are diagnosed with LGSOC in the advanced stages, and 70% of women with stage II-IV disease will relapse in their lifetime. It became a necessity that we find a novel therapeutic that would help improve outcomes for this patient population,“ stated David Gershenson, MD, of the University of Texas MD Anderson Cancer Center and the Lead Author of the NRG-GOG 0281 abstract presentation.
NRG-GOG 0281 assessed whether trametinib, as a potential novel therapeutic, could improve PFS outcomes for women diagnosed with LGSOC. Eligible, consenting patients were randomly assigned to receive either trametinib daily or one of five standard of care treatments including: paclitaxel, PLD, topotecan, letrozole, or tamoxifen) until disease progression. Patients who exhibited disease progression while receiving the standard of care treatment were allowed to crossover and receive trametinib.
Researchers evaluated 260 patients who participated on NRG-GOG 0281. Almost 50% of patients had received 3 or more lines of prior therapy. PFS showed statistically significant improvement for the women who received trametinib when compared to standard of care (median, 13.0 vs 7.2 mo; HR 0.48; 95% CI, 0.36-0.64; P < .0001). Median followup time was 31.4 months. The ORR was 26.2% for trametinib and 6.2% for standard of care (Odds Ratio 5.40; 95% CI, 2.39-12.21; P < .0001). Response duration for trametinib was longer over the standard of care treatment arm (median, 13.63 mo; 95% CI, 8.08-18.76; vs 5.88 mo; 95% CI, 2.76-12.19). Preliminary analysis of the quality of life patient-reported outcomes showed no clinically meaningful treatment effects. Most grade 3 or higher toxicities included skin rash, GI side effects (nausea, diarrhea, constipation, abdominal pain, and emesis), anemia, and hypertension. Dr. Gershenson indicated that the findings of this study suggest that trametinib represents a new standard of care treatment option for women with recurrent low-grade serous carcinoma.
This project was supported by grants P50CA083639 and U10CA180868 from the National Cancer Institute (NCI), part of the Nationals Institutes of Health, and trametinib was supplied by Novartis through the Cooperative Research and Development Agreement (CRADA) with NCI.
Citation
Gershenson DM, Miller A, Brady W, Paul J, Carty W, Rodgers D, Millan D, Coleman RL, Moore KN, Banerjee S, Connolly K, Secord AA, O’Malley DM, Dorigo O, Gaillard S, Gabra H, Hanjani P, Huang H, Wenzel L, Gourley C. (2019, September). A Randomized Phase II/III Study to Assess the Efficacy of Trametinib in Patients with Recurrent or Progressive Low-Grade Serous Ovarian or Peritoneal Cancer. Paper presented at the European Society for Medical Oncology Congress 2019, Barcelona, Spain.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network. www.nrgoncology.org