Olaparib treatment (Tx) in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Overall survival (OS) results from the phase II LIGHT study.

Authors

null

Cara Amanda Mathews

Program in Women’s Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University, Providence, RI

Cara Amanda Mathews , Fiona Simpkins , Karen Anne Cadoo , Ying L Liu , Diane M. Provencher , Colleen McCormick , Adam ElNaggar , Alon D Altman , Lucy Gilbert , Destin Black , Nashwa Kabil , James Bennett , Jiefen Munley , Judy Yu , Carol Aghajanian

Organizations

Program in Women’s Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University, Providence, RI, Department of Obstetrics and Gynecology, Jordan Center for Gynecologic Oncology at the Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, Memorial Sloan Kettering Cancer Center, New York, NY, Centre Hospitalier de l'Université de Montréal (CHUM), Division of Gynecologic Oncology, Montréal, QC, Canada, Legacy Gyencologic Oncology, Portland, OR, West Cancer Center and Research Institute, Memphis, TN, CancerCare Manitoba, Research Institute of Oncology and Hematology, University of Manitoba, Winnipeg, MB, Canada, Division of Gynecologic Oncology, McGill University Health Centre, Montreal, QC, Canada, Willis-Knighton Cancer Center, Shreveport, LA, AstraZeneca, Gaithersburg, MD, AstraZeneca, Cambridge, United Kingdom, AstraZeneca, Wilmington, DE

Research Funding

Pharmaceutical/Biotech Company
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Background: LIGHT (NCT02983799) evaluated olaparib Tx in pts with PSR OC in cohorts with known BRCAm and HRD status. We report the final OS analyses. Methods: We conducted anopen-label, non-randomized, multicenter study of pts with PSR OC and ≥1 prior line of platinum-based chemotherapy (CTx). Pts were assigned to one of 4 cohorts: germline (g) BRCAm; somatic (s) BRCAm; HRD +ve (non-BRCAm); and HRD -ve. Genomic instability score (GIS) and gBRCAm status were determined by Myriad myChoice and BRACAnalysis CDx tests, respectively. HRD +ve tumors were defined by a GIS ≥42. Pts received olaparib Tx (starting dose 300 mg bid) until disease progression or unacceptable toxicity. OS was a secondary endpoint and was analyzed at 12 months (mo) after the primary analysis and 18 mo after the last pt was enrolled. Safety was assessed in pts who received ≥1 dose. Results: Data cut-off (DCO) was Aug 27, 2020. Of 272 enrolled pts, 271 received olaparib; of these, 270 had measurable disease at baseline and were included in efficacy analyses (Table). At DCO, 40% of pts had died (maturity) with a median follow-up in censored pts of 26.3 mo. Kaplan–Meier 18-mo OS rates were 86%, 88%, 79%, and 60% in the gBRCAm, sBRCAm, HRD +ve (non-BRCAm), and HRD -ve cohorts, respectively. Platinum-based CTx was the most common first subsequent Tx and was received by 39% pts after olaparib discontinuation. At DCO, the median duration of Tx was 7.4 mo and 244 pts had discontinued treatment, mainly due to disease progression (72%); 5% discontinued due to treatment-emergent adverse events (TEAEs). The only TEAE leading to discontinuation in >1 pt was nausea (2 pts). Serious TEAEs were reported in 25% of pts. The most common serious TEAE was small intestinal obstruction (6%). Three adverse events of special interest occurred, each in 1 pt (<1%): acute myeloid leukemia (post discontinuation), pneumonitis, and pulmonary fibrosis. Conclusions: In the final OS analysis, 18-mo OS ranged from 60–88% across the 4 cohorts. Consistent with the primary analysis, the 18-mo OS rate was highest in the BRCAm cohorts (similar OS in g and sBRCAm); among pts without a BRCAm, 18-mo OS was highest in the HRD +ve cohort. No new safety signals were observed compared with the primary analysis and with prior olaparib studies. Clinical trial information: NCT02983799

OS and subsequent Tx summary.

gBRCAm

(n=75)
sBRCAm

(n=25)
HRD +ve

(non-BRCAm)

(n=68)
HRD -ve

(n=89)
Overall

(N=270)*
Deaths, n (%)
20 (27)
5 (20)
24 (35)
51 (57)
107 (40)
Alive at 18 mo (%) (95% CI)
86.4

(76.2–92.4)
88.0

(67.3–96.0)
78.6

(66.6–86.8)
59.6

(48.6–68.9)
74.3

(68.5–79.1)
Received subsequent Tx, n (%)
27 (36)
8 (32)
38 (56)
50 (56)
128 (47)
Platinum-based CTx as first subsequent  Tx, n (%)
21 (28)
8 (32)
31 (46)
41 (46)
106 (39)

*13 pts with a Myriad test result of failed or missing were included. CI, confidence interval.

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Clinical Trial Registration Number

NCT02983799

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 5515)

DOI

10.1200/JCO.2021.39.15_suppl.5515

Abstract #

5515

Abstract Disclosures