Outcomes of First-line Olaparib Mono-maintenance therapy-a Multicenter, Retrospective Study Using Data From Real-world Clinical Setting

Outcomes of First-line Olaparib Mono-maintenance Therapy in Newly Diagnosed Ovarian Cancer Patients With tBRCA Wild-type Tumors: a Realworld Study

Four phase III trials in ovarian cancer consistently showed that front-line poly(ADP-ribose) polymerase (PARP) inhibition can significantly improve progression-free survival. Based on these findings, current clinical guidelines recommend the olaparib + bevacizumab combination as a maintenance therapy for ovarian cancer patients with BRCA1/2 wild-type or unknown mutation status who have a complete response (CR)/ partial response (PR) after completing bevacizumab-containing first-line therapy. However, bevacizumab is not a NATIONAL MEDICAL PRODUCTS ADMINSTRATION（NMPA）-approved agent for ovarian cancer patients. In this setting, olaparib mono-maintenance therapy has been implemented among patients with BRCA-wild type tumors in clinical practice in China.

Study Overview

• Status: Not yet recruiting
• Conditions: Ovarian Neoplasms
• Intervention / Treatment: Drug: Olaparib mono-maintenance therapy

Detailed Description

The main objective is to evaluate the outcome of olaparib-based maintenance therapy by proportion of patients alive and progression free at 1 year (1-yr PFS rate) We hypothesize that olaparib monotherapy could be beneficial for tBRCAwt high-grade serous ovarian cancer (HGSOC) patients who are treated with platinum-based first-line chemotherapy.

The secondary objectives are to evaluate the outcomes of olaparib-based maintenance therapy by: 1) 2-yr PFS rate; 2) median PFS; 3) median Time to First Subsequent Therapy or death (mTFST) ; 4) post-progression treatment after first progression; 5) reason for olaparib dose adjustment, dose interruptions, and dose discontinuations; 6) Reason for use of concomitant therapy.

The exploratory objective is to evaluate the status quo of genetic testing, R0 resection and related outcomes.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Zhong-qiu Lin, MD, PhD, Professor; Phone Number: (86) 020-34078521; Email: zhongqiu_lin163@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with HGSOC who started first-line PARPi maintenance therapy from Aug 2018 up to Dec 2020 (the time range could be extended in order to recruit enough eligible subjects as required) will be identified from the electronic medical record system.

Description

Inclusion Criteria:

Patients are eligible to be included in the study only if they met all the following criteria:

• Female Patients must be ≥18 years old at diagnosis.
• Patients with newly diagnosed, histologically confirmed, advanced (FIGO stage III-IV) ovarian cancer, primary peritoneal cancer and / or fallopian-tube cancer and received olaparib from Aug 2018 up to Dec 2020 (the time range could be extended in order to recruit enough eligible subjects as required).
• Patients must have a tumor BRCA testing result which is tBRCAwt, defined as tumor BRCA wild type (patients without evidence of BRCA 1 and/or BRCA 2 deleterious or suspected deleterious mutations).
• Patients who have completed first-line platinum-based chemotherapy and were in clinical complete response (CR) or in partial response (PR).
• Patients who were still in CR or PR before receiving maintenance therapy.
• Patients who received at least one dose of olaparib tablets monotherapy as maintenance therapy within three months after platinum-based chemotherapy and without disease progression.

Exclusion Criteria:

Patients are excluded if any of the following factors were present:

• Patient with multiple primary cancers as reported in EMR.
• Concomitant any anti- cancer therapy (chemotherapy, immunotherapy, hormonal therapy (Hormone replacement therapy (HRT) is acceptable), radiotherapy, biological therapy or other novel agent) during Olaparib maintenance.
• Any previous treatment with PARP inhibitor.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Patients with symptomatic uncontrolled brain metastases.
• Any other concerns related to decreased efficacy and safety of maintenance therapy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Olaparib mono-maintenance therapy group; Olaparib monotherapy in clinical practice and will be conducted in patients with tBRCAwt newly diagnosed high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy following the standard of care from Aug 2018 up to Dec 2020 (the time range could be extended in order to recruit enough eligible subjects as required) at tertiary-referral university hospitals and main cancer centers in China.

Drug: Olaparib mono-maintenance therapy; Olaparib mono-maintenance therapy in patients with newly diagnosed, histologically confirmed, advanced (FIGO stage III-IV) ovarian cancer, primary peritoneal cancer and / or fallopian-tube cancer is defined as drug exposure. At least one dose of olaparib tablets monotherapy as maintenance therapy will be required.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-yr PFS rate	The main objective is to evaluate the outcome of olaparib-based maintenance therapy by proportion of patients alive and progression free at 1 year.	12 months after date of first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-yr PFS rate	The proportion of patients alive and progression free by 2 years by investigator assessed clinical progression	24 months after date of first dose
Median PFS	Median time from date of first dose until disease progression per clinical progression (mPFS) as assessed by the investigator at local site or death due to any cause (if this occurs before disease progression)	Median time from date of first dose until disease progression
mTFST	Median Time to First Subsequent Therapy or death	Median time from date of first dose to the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of treatment or death due to any cause
post-progression treatment after first progression	The proportion of patients receiving each treatment after first progression	The proportion of patients receiving each treatment after first progression
Reason for olaparib dose adjustment, dose interruptions, and dose discontinuations	The proportion of olaparib dose adjustment, dose interruptions, and dose discontinuations	The proportion of olaparib dose adjustment, dose interruptions, and dose discontinuations
Reason for use of concomitant therapy	The proportion of concomitant therapy	The proportion of concomitant therapy

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Study Chair: Zhong-qiu Lin, MD, PhD,Professor, Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Principal Investigator: Jing Li, MD, PhD,Professor, Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): December 10, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: tBRCA， olaparib
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: ESR-20-20889-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No