What it is
Ovarian clear cell carcinoma is a rare but aggressive subtype of ovarian cancer in which PIK3CA mutations are common, and after platinum-based chemotherapy fails, options are limited. This single-arm phase 2 trial at 27 centres in China and 12 in Japan gave the oral PI3Kα inhibitor risovalisib, 40 mg daily, to adults with recurrent or persistent PIK3CA-mutated disease after one to three previous lines of treatment. Of 93 patients enrolled, 68% had had two or more previous lines. At a median follow-up of 14.5 months, tumours responded, as judged by a blinded independent review committee, in 29 of 84 patients with a confirmed hotspot mutation and measurable disease, a response rate of 35% (95% confidence interval 25-46%), above the trial's bar that the interval's lower bound exceed 8%. The most common grade 3 or worse treatment-related adverse events were rash (32%), high blood sugar (30%) and weight loss (8%); serious treatment-related adverse events occurred in 39% of patients, and there were no treatment-related deaths.
Why it matters
A rare, hard-to-treat ovarian cancer may gain a targeted option: a PI3Kα-inhibitor pill shrank PIK3CA-mutated tumours in about a third of the patients evaluated for response. Most had already been through two or more lines of treatment, responses were judged by blinded independent review, and the primary endpoint cleared the trial's stated bar. The authors call risovalisib a potential novel treatment option for a rare yet lethal cancer, and suggest exploring combinations that include it to raise the response further.
Underlined numbers link to their source. Every metric and quoted figure is listed under Sources and data below.
Filed underOvarian cancer diagnosis and treatment, PI3K/AKT/mTOR signaling in cancer, PARP inhibition in cancer therapy
