| 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. |
| Authors: |
Liu, Ying L.1,2 (AUTHOR) liuy3@mskcc.org, Mathews, Cara A.3 (AUTHOR), Simpkins, Fiona4 (AUTHOR), Cadoo, Karen A.1,5 (AUTHOR), Provencher, Diane6 (AUTHOR), McCormick, Colleen C.7,8 (AUTHOR), ElNaggar, Adam C.9 (AUTHOR), Altman, Alon D.10 (AUTHOR), Gilbert, Lucy11 (AUTHOR), Black, Destin12 (AUTHOR), Kabil, Nashwa13 (AUTHOR), Taylor, Rosie N.14 (AUTHOR), Barnicle, Alan14 (AUTHOR), Munley, Jiefen Y.15 (AUTHOR), Aghajanian, Carol1,2 (AUTHOR) |
| Source: |
Cancer (0008543X). 1/15/2025, Vol. 131 Issue 2, p1-12. 12p. |
| Subject Terms: |
*OLAPARIB, *BRCA genes, *OVARIAN cancer, *HOMOLOGOUS recombination, *TUMORS, *CLINICAL trials, *OVERALL survival |
| 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. The LIGHT study final overall survival results highlight that olaparib is active in all patients with platinum‐sensitive relapsed ovarian cancer, particularly those with homologous recombination deficiency‐positive tumors. Consistent with the LIGHT primary analysis, the highest overall survival rates were observed in patients with a germline or somatic BRCA mutation. Plain Language Summary: The LIGHT (oLaparib In HRD‐Grouped Tumor types; NCT02983799) study explored the use of olaparib therapy for women with relapsed ovarian cancer. Patients were grouped according to whether their tumor had a BRCA gene mutation (BRCAm) and other genetic changes that impaired the cancer cell's ability to repair DNA damage, known as homologous recombination deficiency (HRD).This final survival analysis showed that 18 months after start of olaparib, more patients with a BRCAm were alive than those without a BRCAm. For patients without a BRCAm, more patients who tested positive for HRD were alive 18 months after start of olaparib than patients who tested negative for HRD. [ABSTRACT FROM AUTHOR] |
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