A Novel, Personalized Drug-Screening System for Platinum-Resistant Ovarian Cancer Patients: A Preliminary Clinical Report

Abstract

Purpose

With this study, we intended to construct a personalized drug-screening system for platinum-resistant ovarian cancer patients by consulting a patient’s medical history, data derived from gene mutation detection, and drug screening results derived from mini-PDX (patient-derived xenograft) models. We also aimed to evaluate the efficacy and safety of our system.

Patients and Methods

We selected 12 patients with platinum-resistant ovarian cancer who were treated at our hospital from January 2018 to December 2019 to design a single-arm clinical trial. The subsequent chemotherapeutic plans were selected according to a personalized drug-screening system that circulating tumor DNA (ctDNA) testing and the establishment of mini-PDX models. We then analyzed the patients for clinical benefits side-effects in response to chemotherapy in order to evaluate the clinical effects and safety of our new personalized drug-selection system.

Results

We successfully established an individualized and sensitive drug-screening system for the 12 patients. Mini-PDX models verified that potentially effective drugs were identified for 11 of the patients. Treatment resulted in complete remission (one patient), partial remission (five patients), and stable disease (three patients). The remaining three patients experienced disease progression. The overall clinical-benefit rate was 75.0%. Following treatment, the levels of CA125 levels decreased significantly in seven of the 12 patients. Severe side effects, arising from chemotherapy, were only observed in one case.

Conclusion

Constructing a personalized drug-screening system for platinum-resistant ovarian cancer patients can be used to guide clinical drug selection and improve the clinical-benefit rate for patients.

Trial Registration Number

ChiCTR1800016766 (Chinese Clinical Trial Registry Center).

Keywords:

• drug resistance
• ovarian cancer
• precision medicine
• personalized drug-screening system

Acknowledgments

This research was supported by National Key R&D Program of China:2016YFC1303102 Science and Technology Commission of Shanghai Municipality: 18140902502; 18411963300 Shanghai Health and Medical Development Foundation: 122018BR26; ZYKC201701020 Shanghai Shenkang Hospital Clinical Development Plan: SHDC12018X13 Lianyu Lin’s work on ctDNA tests at the central laboratory of Topgen Bio-Pharm Co, Ltd., sequencing with OncoDrug-SeqTM (Topgen-Biopharm, shanghai, China) was appreciated by all the authors.

Data Sharing Statement

The authors (Yunke Huang, [email protected]; Yu Kang, [email protected]) would share the clinical data with all the researchers, the clinical trial data (including age, medical history, pathological examinations, imaging examination results, mutation detection results, mini-PDX drug sensitivity results, follow-up results, etc) would be uploaded to ResMan (www.medresman.org) right after publication of the article. The clinical protocol would also be attached for reference.

Ethics Approval

The present study was approved by the Ethical Committee of the Obstetrics & Gynecology Hospital of Fudan University (approval number:2016-51-X1).

Consent to Participate

Written informed consent was provided by all participants before enrollment.

Consent to Publication

All the authors agree with the publication of this article.

Disclosure

The authors confirm that there are no conflicts of interest.