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
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
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.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2020 ASCO Virtual Scientific Program
First Author: Karen Anne Cadoo
2022 ASCO Annual Meeting
First Author: Sandro Pignata
2020 ASCO Virtual Scientific Program
First Author: Andres Poveda
2023 ASCO Annual Meeting
First Author: Katrin Marie Sjoquist