Olaparib combined with tremelimumab missed the planned efficacy target in a phase I/II trial involving 50 women with recurrent cancer and inherited BRCA variants. Some participants had prolonged disease control, but severe side effects were frequent. The newly published peer-reviewed study used one treatment arm, so it cannot determine whether the combination works better than either drug alone.
The combination of olaparib and tremelimumab missed its prespecified efficacy endpoint in a peer-reviewed phase I/II ovarian-cancer study. The overall response rate was 32.7 percent. Sarah F. Adams and colleagues enrolled 50 women whose recurrent ovarian, fallopian-tube or primary peritoneal cancer accompanied inherited variants in BRCA1 or BRCA2. Every participant was offered the same treatment combination.[1]
Olaparib interferes with a DNA-repair enzyme; tremelimumab targets CTLA4, an immune checkpoint that regulates immune responses. Among 49 participants receiving at least one dose, 57 percent experienced severe non-hematologic toxicity. Tremelimumab was discontinued by 34.7 percent. The infusion schedule was revised following delayed immune-related toxicity. No death was directly attributed to treatment.[1]
Six participants remained free of progression for more than 12 months. Tumour gene-expression analyses also found exploratory associations involving VSTM5 and IFIT1B, but did not provide a validated treatment-selection test. With no comparison arm, the trial cannot establish an advantage over either drug alone. Previous exposure and resistance to related drugs further complicate interpretation of this single study.[1]
