Clinical trial NCT05153603: Outcomes of First-line Olaparib Mono-maintenance therapy-a Multicenter, Retrospective Study Using Data From Real-world Clinical Setting
Official title: Outcomes of First-line Olaparib Mono-maintenance Therapy in Newly Diagnosed Ovarian Cancer Patients With tBRCA Wild-type Tumors: a Realworld Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Ovarian Neoplasms
Keywords: tBRCA， olaparib
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2021-12-10
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 1-yr PFS rate
timeFrame: 12 months after date of first dose
Secondary outcomes:
measure: 2-yr PFS rate
timeFrame: 24 months after date of first dose
measure: Median PFS
timeFrame: Median time from date of first dose until disease progression
measure: mTFST
timeFrame: 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
measure: post-progression treatment after first progression
timeFrame: The proportion of patients receiving each treatment after first progression
measure: Reason for olaparib dose adjustment, dose interruptions, and dose discontinuations
timeFrame: The proportion of olaparib dose adjustment, dose interruptions, and dose discontinuations
measure: Reason for use of concomitant therapy
timeFrame: The proportion of concomitant therapy
Other outcomes:
Locations:
Study officials:
affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
name: Zhong-qiu Lin, MD, PhD,Professor
role: STUDY_CHAIR
affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
name: Jing Li, MD, PhD,Professor
role: PRINCIPAL_INVESTIGATOR
References: