Headline: For the first time, a clear clinical advantage is demonstrated with upfront PARP inhibition for BRCA-mutated advanced ovarian cancer.
The Study: PARP inhibition has lots of good theoretical reasons to work on BRCA-mutated cancers and even has clinical data supporting its use in relapsed BRCA-mutated ovarian cancer. More recently the phase 3 SOLO1 trial randomized 391 women who responded well (i.e., ≥30% disease reduction) with first-line platinum-based chemo to maintenance placebo versus PARP inhibition with olaparib 300 mg PO twice daily for at least 2 years. Of note, all but two enrollees had germline BRCA mutations, and the vast majority (82%) had complete radiographic and biochemical (CA-125) responses to chemo. At 3 years, there was an absolute benefit of 33% in the primary endpoint of rate of progression-free survival from 27 → 60%. This translated to an impressive hazard ratio of 0.3 that held across every single subset. Looking at it another way, median time to salvage therapy or death was increased from 15 → 52 months! As expected, rates of G3-4 toxicity were increased compared to placebo from 18 → 39% comprised primarily of anemia.  PFS as an endpoint has gotten a bad rap recently, but with differences this dramatic we’d be surprised if overall survival doesn’t follow suit.
Bottom Line: Upfront maintenance olaparib for germline BRCA-mutated ovarian cancer results in unprecedented PFS times. | Moore, N Engl J Med 2018


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