The invited discussant of the phase III INOVATYON trial was Andreas du Bois, MD, PhD, Chairman of the Department of Gynecology and Gynecologic Oncology at Kliniken Essen Mitte, Germany, and Chairman of the AGO Study Group. As Dr. du Bois explained, the study “dealt with an old question: Does prolonging the platinum-free interval enhance the efficacy of platinum retreatment? Is a platinum-free interval a targetable effort?”
Investigators have long wondered whether the use of a nonplatinum combination after relapse—switching to platinum only after second relapse or disease progression—might enhance platinum sensitivity and prove more effective than immediately rechallenging with a platinum, as is customary. The 2017 MITO-8 study was the first to evaluate this idea, and the results were negative.1 The discussion then became whether the right experimental arm had been selected, which led to the ultimate evaluation of trabectedin plus pegylated liposomal doxorubicin in INOVATYON.
“Again, we have a negative study,” stated Dr. du Bois. “The standard approach of rechallenging the patient with a platinum showed a significantly better progression-free survival, with less toxicity and less detrimental impact on quality of life.”
“Finally, the question that’s been discussed for almost 30 years has been solved,” he said. “Platinum-based regimens remain the standard of care in patients with recurrent ovarian cancer progressing within 6 to 12 months after their last platinum line.”
New Questions Arise
“But answering one question opens new ones,” Dr. du Bois continued. “Although prolonging the platinum-free interval with chemotherapy does not work, what about prolonging it with a PARP inhibitor, bevacizumab, other biologics and combinations, or surgery? What about shortening the treatment-free interval by using more sensitive diagnostics, such as cell-free DNA, to detect earlier relapse and introduce new treatments to control disease? One question has been answered—and that’s an important step—but new questions are now raised.”
DISCLOSURE: Dr. du Bois reported financial relationships with AstraZeneca, BioCad, Clovis Oncology, Doxolipad, Genmab, Ingress Health, Roche/Genentech, and Tesaro.
1. Pignata S, Scambia G, Bologna A, et al: Randomized controlled trial testing the efficacy of platinum-free interval prolongation in advanced ovarian cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study. J Clin Oncol 35:3347-3353, 2017.
Yet another blow has been dealt for the alkylating agent trabectedin in advanced ovarian cancer. The international phase III INOVATYON study found no improvement in overall or progression-free survival for trabectedin plus pegylated liposomal doxorubicin (PEG-LD) vs carboplatin/PEG-LD in patients...