Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer.

Autor:	Coffman LG; Magee-Womens Research Institute, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA.; Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, and., Orellana TJ; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Liu T; Division of General Internal Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA., Frisbie LG; Department of Integrative Systems Biology and., Normolle D; Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Griffith K; Center for Cancer Data Sciences, Rogel Cancer Center, and., Uppal S; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA., McLean K; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA., Berger J; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Boisen M; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Courtney-Brooks M; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Edwards RP; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Lesnock J; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Mahdi H; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Olawaiye A; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Sukumvanich P; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Taylor SE; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA., Buckanovich R; Magee-Womens Research Institute, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA.; Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, and.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2022 Sep 22; Vol. 7 (18). Date of Electronic Publication: 2022 Sep 22.
DOI:	10.1172/jci.insight.160573
Abstrakt:	BACKGROUNDNew therapeutic combinations to improve outcomes of patients with ovarian cancer are clearly needed. Preclinical studies with ribociclib (LEE-011), a CDK4/6 cell cycle checkpoint inhibitor, demonstrate a synergistic effect with platinum chemotherapy and efficacy as a maintenance therapy after chemotherapy. We tested the safety and initial efficacy of ribociclib in combination with platinum-based chemotherapy in recurrent ovarian cancer.METHODSThis phase I trial combined weekly carboplatin and paclitaxel chemotherapy with ribociclib, followed by ribociclib maintenance in patients with recurrent platinum-sensitive ovarian cancer. Primary objectives were safety and maximum tolerated dose (MTD) of ribociclib when given with platinum and taxane chemotherapy. Secondary endpoints were response rate (RR) and progression-free survival (PFS).RESULTSThirty-five patients were enrolled. Patients had a mean of 2.5 prior lines of chemotherapy, and 51% received prior maintenance therapy with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab. The MTD was 400 mg. The most common adverse events included anemia (82.9%), neutropenia (82.9%), fatigue (82.9%), and nausea (77.1%). The overall RR was 79.3%, with a stable disease rate of 18%, resulting in a clinical benefit rate of 96.6%. Median PFS was 11.4 months. RR and PFS did not differ based on the number of lines of prior chemotherapy or prior maintenance therapy.CONCLUSIONThis work demonstrates that the combination of ribociclib with chemotherapy in ovarian cancer is feasible and safe. With a clinical benefit rate of 97%, this work provides encouraging evidence of clinical efficacy in patients with recurrent platinum-sensitive disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03056833.FUNDINGThis investigator-initiated trial was supported by Novartis, which provided drugs and funds for trial execution.
Databáze:	MEDLINE
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