Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis Journal Article

   

Authors:	Liu, Y. L.; Mathews, C. A.; Simpkins, F.; Cadoo, K. A.; Provencher, D.; McCormick, C. C.; ElNaggar, A. C.; Altman, A. D.; Gilbert, L.; Black, D.; Kabil, N.; Taylor, R. N.; Barnicle, A.; Munley, J. Y.; Aghajanian, C.
Article Title:	Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis
Abstract:	Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS). Methods: In this phase 2, open-label, noncomparative study, patients with PSROC and one or more prior line of platinum-based chemotherapy were assigned to cohorts by BRCAm and HRD status. OS was a secondary end point. Tumors were analyzed using Myriad BRACAnalysis CDx and MyChoice CDx assays; HRD-positive tumors were defined using a genomic instability score of ≥42. Results: Of 272 enrolled patients, 271 received olaparib and 270 met the inclusion criteria for the efficacy analysis. At data cutoff, 18-month OS rates in the gBRCAm, sBRCAm, HRD-positive non-BRCAm, and HRD-negative cohorts were 86.4%, 88.0%, 78.6%, and 59.6%, respectively. No new safety signals were observed. In a post hoc analysis, patients on treatment for >18 months were most frequently present in g/sBRCAm cohorts (31.0%). Conclusions: Olaparib treatment continued to demonstrate benefit across all cohorts. Consistent with the primary analysis, the highest OS rates were observed in the BRCAm cohorts, regardless of g/sBRCAm. In patients without a BRCAm, a higher OS rate was observed in the HRD-positive non-BRCAm than the HRD-negative cohorts. These results highlight the importance of biomarker testing in this treatment setting. © 2025 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
Keywords:	adult; aged; aged, 80 and over; middle aged; survival analysis; gene mutation; major clinical study; overall survival; genetics; mutation; lenalidomide; clinical trial; drug tolerability; fatigue; mortality; bevacizumab; cisplatin; doxorubicin; placebo; drug efficacy; drug safety; gemcitabine; paclitaxel; topotecan; outcome assessment; follow up; prospective study; prospective studies; ovarian neoplasms; dna damage; homologous recombination; carboplatin; progression free survival; ovary cancer; phase 2 clinical trial; neoplasm recurrence, local; breast cancer; anemia; prevalence; cohort analysis; relapse; brca1 protein; brca2 protein; cancer therapy; docetaxel; abdominal pain; asthenia; lung embolism; myelodysplastic syndrome; genomic instability; multicenter study; tumor recurrence; ovary tumor; carcinoma; platinum; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; double stranded dna break; piperazines; drug therapy; piperazine derivative; chromosome analysis; atrial fibrillation; brca1 protein, human; antiviral resistance; olaparib; non small cell lung cancer; cytochrome p450 2d6; phthalazine derivative; phthalazines; brca mutation; acute myeloid leukemia; seroconversion; fallopian tube; endoplasmic reticulum stress; high throughput sequencing; enzalutamide; brca2 protein, human; niraparib; rucaparib; very elderly; humans; human; female; article; medical dictionary for regulatory activities; poly(adp-ribose) polymerase inhibitors; homologous recombination deficiency; ovarian epithelial
Journal Title:	Cancer
Volume:	131
Issue:	2
ISSN:	0008-543X
Publisher:	Wiley Blackwell
Date Published:	2025-01-15
Start Page:	e35707
Language:	English
DOI:	10.1002/cncr.35707
PUBMED:	39817648
PROVIDER:	scopus
PMCID:	PMC11736996
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85214977493&doi=10.1002%2fcncr.35707&partnerID=40&md5=94e1741d30615bcfd2d6ac6bc1f2fa93
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Ying L. Liu -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/222137