Exploratory hrd and PD-L1 analysis of l-MOCA study: Olaparib maintenance monotherapy in Asian patients with platinum-sensitive relapsed ovarian cancer.

Authors

null

Ding Ma

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Ding Ma , Qing-lei Gao , Jianqing Zhu , Weidong Zhao , Yi Huang , Ruifang An , Hong Zheng , Pengpeng Qu , Li Wang , Qi Zhou , Danbo Wang , Ge Lou , Jing Wang , John Low , Beihua Kong , Rutie Yin , Xing Xie , Jihong Liu , Wei Sun , Rongyu Zang

Organizations

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Tongji Hospital, Tongji Medical College Huazhong University of Science & Technology, Wuhan, China, Cancer Hospital of The University of Chinese Academy of Sciences, Hangzhou, China, Anhui Provincial Cancer Hospital, Hefei, China, Hubei Cancer Hospital, Wuhan, China, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, China, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China, Department of Gynecological Oncology, Chongqing University Cancer Hospital, Chongqing, China, Liaoning Cancer Hospital, Shenyang, China, Gynecology Ward 1, Harbin Medical University Cancer Hospital, Harbin, China, Hunan Cancer Hospital, Changsha, China, Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, Qilu Hospital of Shandong University, Jinan, China, Department of Gynecology and Obstetrics, and Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China, Sun Yat-sen University Cancer Center, Guangzhou, China, Anhui Provincial Cancer Hospital,, Hefei, China, Zhongshan Hospital, Fudan University, Shanghai, China

Research Funding

Pharmaceutical/Biotech Company

Background: Olaparib demonstrated its efficacy to prolong progression-free survival (PFS) in platinum-sensitive relapsed ovarian cancer (PSROC) patients (L-MOCA study). Almost half of OC patients harbor homologous recombination deficiencies (HRD). However, there is lack of the HRD prevalence in Asian PSR population. Meanwhile, Immunological processes play a key role in tumorigenesis and PD-L1 status may hinder an effective antitumor immune response in OC. Herein, we analyzed HRD and PD-L1 status in Asian patients with PSROC, and explored Olaparib response to different HRD status. Methods: In this exploratory analysis of L-MOCA trial, HRD and PD-L1 status were analyzed from patients with PSROC. Residual DNA samples of 193 patients were analyzed for HRD status with a local developed HRD assay (Teddy Laboratory, Shanghai, China, which determines two major components, tBRCA1/2 status and LOH score, HRD positive indicates the presence of a deleterious or suspected deleterious BRCA mutation or LOH score ≥0.4). The remaining formalin fixation and paraffin embedded samples were used for PD-L1 expression analysis by immunohistochemistry with SP263. Descriptive statistics were summarized for HRD status, PD-L1 expression status and PFS by different HRD status subgroups. Results: 193 of 224 patients had residual DNA for HRD test. Patients clinical characteristics were similar between those with and without residual DNA for HRD test, in terms of age (mean age 55.5y Vs 54.2y), FIGO stage (stage III 68.9% Vs 61.3%, stage IV 12.4% Vs 22.65%), and time to disease progression to Last prior Platinum Based Chemotherapy (6-12m: 39.9% Vs 41.9%; > 12m: 59.6% Vs 54.8%). Among 193 patients with HRD test conducted, proportion of HRD+ BRCAm, HRD+ BRCAwt, HRD- and HRD unknown were 37.3%, 28.0%, 14.5% and 20.2%, separately. mPFS of the above subgroups was 20.1 months, 15.8 months, 9.2 months and 16.4 months, respectively (Table1). 200 of 224 patients were available for PD-L1 expression analysis. 184 (92%) with TC<1%, 12 (6%) with TC among 1-25%. These results showed TC expression in all patients were less than 25%, suggesting that ovarian cancer may be an immunologically cold tumor. Conclusions: This is firstly showing the HRD and PD-L1 status in Asian OC patients. The results showed all the PSR patients could benefit from Olaparib treatment, regardless of HRD status. Meanwhile the numerically different mPFS observed across different HRD status subgroups also indicated potential clinical utility of locally developed HRD assay. Clinical trial information: NCT03534453.


HRD+ BRCAm

(N = 72)
HRD+ BRCAwt (N = 54)
HRD- (N = 28)
HRD unknown

(N = 39)
Patients With PFS events, n (%)
36(50.0)*
35(64.8)*
23 (82.1)*
27 (69.2)*
mPFS, months

(95% CI)
20.1 (15.6-NA)
15.8 (6.9-22.1)
9.2 (7.5–13.8)
16.4 (7.5-20.8)

**Calculated based on the number of patients in each subgroup. mPFS, median progression-free survival.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Clinical Trial Registration Number

NCT03534453

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr e17578)

DOI

10.1200/JCO.2022.40.16_suppl.e17578

Abstract #

e17578

Abstract Disclosures

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