Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis Journal Article

   

Authors:	Cadoo, K.; Simpkins, F.; Mathews, C.; Liu, Y. L.; Provencher, D.; McCormick, C.; ElNaggar, A. C.; Altman, A. D.; Gilbert, L.; Black, D.; Kabil, N.; Bennett, J.; Munley, J.; Aghajanian, C.
Article Title:	Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis
Abstract:	Objective: Olaparib treatment resulted in significant improvement in objective response rates (ORRs) and progression-free survival (PFS) over non‐platinum chemotherapy in patients with BRCA1/BRCA2-mutated (BRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) and ≥2 prior lines of platinum-based chemotherapy in the phase III SOLO3 study. LIGHT (NCT02983799) prospectively evaluated olaparib treatment for patients with PSROC and known BRCAm and homologous recombination deficiency (HRD) status. Methods: In this phase II open-label multicenter study, patients with PSROC and ≥1 prior line of platinum-based chemotherapy were assigned to cohorts by presence of germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive tumors without BRCAm, or HRD-negative tumors. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR) and PFS. Tumors were analyzed using Myriad BRACAnalysis CDx and myChoice HRD assays; HRD-positive tumors were defined using a genomic instability score of ≥42. Results: Of 272 enrolled patients, 271 received olaparib and 270 were included in efficacy analyses. At data cut-off, ORRs in the gBRCAm, sBRCAm, HRD-positive, and HRD-negative cohorts were 69.3%, 64.0%, 29.4%, and 10.1%, respectively. DCRs were 96.0%, 100.0%, 79.4%, and 75.3% in each cohort, respectively. Median PFS was 11.0, 10.8, 7.2, and 5.4 months, respectively. The most common (≥ 20%) treatment-emergent adverse events included nausea, fatigue/asthenia, vomiting, anemia, constipation, diarrhea, and decreased appetite. Conclusions: Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was observed in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater efficacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies. © 2022 The Authors
Keywords:	adult; cancer chemotherapy; cancer survival; controlled study; aged; unclassified drug; human cell; major clinical study; genetics; mutation; clinical trial; constipation; fatigue; neutropenia; cancer recurrence; diarrhea; drug dose reduction; drug safety; side effect; treatment; prospective study; ovarian cancer; ovarian neoplasms; homologous recombination; progression free survival; antineoplastic metal complex; ovary cancer; phase 2 clinical trial; neoplasm recurrence, local; anemia; nausea; thrombocytopenia; vomiting; cohort analysis; creatinine; creatinine blood level; pathology; brca1 protein; brca2 protein; tumor antigen; abdominal pain; asthenia; coughing; dizziness; dyspnea; pneumonia; genomic instability; multicenter study; tumor recurrence; ovary tumor; open study; headache; piperazines; piperazine derivative; brca; lung fibrosis; atrial fibrillation; olaparib; dysgeusia; phthalazine derivative; phthalazines; decreased appetite; acute myeloid leukemia; cancer antigen 125; humans; human; female; article; homologous recombination deficiency; ecog performance status; carcinoma, ovarian epithelial; herpesvirus entry mediator ligand
Journal Title:	Gynecologic Oncology
Volume:	166
Issue:	3
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2022-09-01
Start Page:	425
End Page:	431
Language:	English
DOI:	10.1016/j.ygyno.2022.06.017
PUBMED:	35803835
PROVIDER:	scopus
PMCID:	PMC9909678
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85133888646&doi=10.1016%2fj.ygyno.2022.06.017&partnerID=40&md5=6fa6b7950b41916d936125a2e8a37f1b
Notes:	Article -- Export Date: 3 October 2022 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/198296