Preliminary results of a phase 1 study showed favorable safety and tolerability of ribociclib, both concurrently with platinum and taxane chemotherapy and as maintenance therapy, with encouraging antitumor activity in patients with recurrent platinum-sensitive ovarian cancer.
A phase 1, open-label, single-institution, dose-escalation trial assessed the safety and efficacy of the cyclin-dependent kinase (CDK)4/6 cell cycle checkpoint inhibitor, ribociclib (LEE-011), in patients with recurrent platinum-sensitive ovarian cancer. Results of this trial were reported at the 2021 Society of Gynecologic Oncology Annual Meeting.
Patients with a diagnosis of recurrent platinum-sensitive ovarian cancer, who had received at least 1 previous platinum-based chemotherapy regimen, were enrolled in the study. Eligible patients received ribociclib (200 mg, 400 mg, or 600 mg on days 1-4, 8-11, and 15-18); and weekly carboplatin (AUC2) and paclitaxel (60 mg/m2) on days 1, 8, and 15 of a 28-day cycle for a planned 6 total cycles. Patients with at least a partial response to therapy received maintenance ribociclib 600 mg daily until time of progression. The primary end point was the maximum tolerated dose (MTD) of ribociclib administered concurrently with platinum and taxane chemotherapy. Secondary end points were response rate and progression-free survival (PFS).
The study enrolled a total of 35 patients. Patients had received a mean of 2.5 previous lines of chemotherapy and 51% had received previous maintenance therapy; of these, 31% had received poly (ADP-ribose) polymerase (PARP) inhibitor therapy, 34.3% had received bevacizumab, and 14.3% had received both. The MTD was established as 400 mg. No dose-limiting toxicities (DLTs) were observed in the 200-mg group; 11 patients (33.3%) in the 400-mg group had DLTs. A higher incidence of grade 3/4 adverse events (AEs) occurred during concurrent therapy (n = 35 events) than during maintenance (n = 9 events). The most frequent AEs included anemia (82.9%), neutropenia (82.9%), fatigue (82.9%), nausea (77.1%), hypertension (62.9%), and thrombocytopenia (40.0%).
In the overall population, response rate was 79.3%, and was similar among patients with and without previous maintenance therapy (82% PARP inhibitor vs 78% without; 83% bevacizumab vs 78% without); and among patients with 1 previous line of chemotherapy versus those with >1 previous line (83% vs 76%). Overall PFS was 11.4 months and was comparable among patients with and without previous maintenance therapy (10.1 vs 14.4 months; P = .07).
Preliminary results of this phase 1 study showed encouraging safety and tolerability of ribociclib, both concurrently with platinum and taxane chemotherapy and as maintenance therapy, with encouraging antitumor activity in patients with recurrent platinum-sensitive ovarian cancer.
Source: Coffman L, Orellana T, Normolle D, et al. Phase I trial of ribociclib (LEE-011) with platinum-based chemotherapy in recurrent platinum sensitive ovarian cancer. Gynecol Oncol. 2021;162(suppl_1):S69.
