Outcomes with a TWiST.

In the phase 3 ENGOT-OV16/NOVA trial, maintenance therapy with the PARP-inhibitor niraparib significantly improved median progression-free survival (PFS) for patients with recurrent ovarian cancer with (6 → 21 months) or without (4 → 9 months) BRCA-mutations. While impressive, critics question how much stock we should really be putting into the popular (and quick to measure) PFS endpoint. This secondary analysis aimed to measure time without symptoms or toxicity (aka TWiST) as a novel endpoint with inherent value. Quantifying this was really quite simple: TWiST = mean PFS - time with toxicity. The latter is measured as the area under the Kaplan-Meier curve for symptomatic toxicities prior to disease progression (i.e., time with toxicities that can be chalked up to treatment rather than to disease). What you’re left with = life free from progressive disease and treatment side effects = inherent goodness. The “mean” (not median) benefits of PFS with niraparib were a whopping 39 and 16 months for the cohorts with and without BRCA-mutations, respectively, and times with toxicity only 3 and 1 months. Therefore, the TWiST benefits with niraparib were roughly 3 and 1 years. The only question remaining: does asymptomatic radiographic progression = inherent badness? Probably not unless overall survival outcomes mature in line with PFS. TBL: Lookout for TWiST as the newest surrogate endpoint in oncology clinical trials. | Matulonis, J Clin Oncol 2019