Surrogate endpoints in platinum-resistant recurrent ovarian cancer
DOI: 10.32364/2587-6821-2022-6-6-319-325
A.A. Rumyantsev1, A.S. Tyulyandina1,2, E.R. Israelyan3, M.Yu. Fedyanin1,4,5, S.L. Gutorov1, S.A Tjulandin1
1N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation
2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
3N.I. Pirogov Russian National Research Medical University, Moscow, Russian Federation
4Moscow Clinical Research Center "Kommunarka", Moscow, Russian Federation
5N.I. Pirogov National Medical and Surgical Center, Moscow, Russian Federation
Background: overall survival (OS) is the gold-standard primary end point for cancer clinical trials to evaluate the outcome of therapy. However, in some cases the direct assessment of OS can be inappropriate. Therefore, various surrogate endpoints, such as overall response rate (ORR) and progression-free survival (PFS), are used commonly in clinical trials. Aim: to assess the relevance of mentioned endpoints in platinum-resistant recurrent ovarian cancer.
Patients and Methods: we used PubMed queries to search for all ovarian cancer studies from 01/01/2000 to 07/01/2019. Key inclusion criteria were: 1) recurrent epithelial ovarian cancer, 2) platinum-free interval ≤6 months, 3) standard chemotherapy (CT) without targeted and/or experimental drugs, 4) reported objective response rate, PFS and OS, as well as response assessment criteria. Correlation and linear regression analysis were conducted to identify the relationship between various markers of therapy efficacy. Trials were weighted according to the number of enrolled patients. Statistical analysis of the data was performed using R and RStudio software.
Results: 7156 studies were reviewed, and 157 studies meeting the inclusion/exclusion criteria were selected. PFS and OS data were available in 104 (n=5081) and 99 (n=5089) studies, respectively. The average ORR was 17.2% (non-platinum CT — 13.6%, platinum-based CT — 36.7%; p<0.001), and median PFS was 3.68 months (3.38 and 5.37 months, respectively; p<0.001). A significant correlation was found between ORR and PFS (r=0.62; p<0.001). Linear regression analysis identified 0.5 months increase in median PFS for every 10% increase in ORR (p<0.001). There was no significant correlation between ORR and OS.
Conclusions: the meta-analysis results provide valuable information for understanding the role of surrogate biomarkers in platinum-resistant recurrent ovarian cancer. ORR is a reliable predictor of PFS in this patient population.
Keywords: ovarian cancer, platinum resistance, chemotherapy, surrogate endpoints, systematic review, meta-analysis.
For citation: Rumyantsev A.A., Tyulyandina A.S., Israelyan E.R. et al. Surrogate endpoints in platinum-resistant recurrent ovarian cancer. Russian Medical Inquiry. 2022;6(6):319–325 (in Russ.). DOI: 10.32364/2587-6821-2022-6-6-319-325.
About the authors:
Alexey A. Rumyantsev — Dr. Sc. (Med.), Senior Research Associate, Department of Chemotherapy No. 4 of the N.N. Trapeznikov Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology; 23, Kashirskoe road, Moscow, 115478, Russian Federation; ORCID iD 0000-0003-4443-9974.
Alexandra S. Tyulyandina — Dr. Sc. (Med.), Head of Department of Chemotherapy No. 4 of the N.N. Trapeznikov Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology; 23, Kashirskoe road, Moscow, 115478, Russian Federation; Professor, Oncology Department of the N.V. Sklifosovskiy Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University); 8 Build. 2, Trubetskaya str., Moscow, 119991, Russian Federation; ORCID iD 0000-0002-6104-7473.
Edgar R. Israelyan — Clinical Resident, Department of Oncology, Pirogov Russian National Research Medical University; 1, Ostrovityanov str., Moscow, 117437, Russian Federation; ORCID iD 0000-0002-6666-549X.
Mikhail Yu. Fedyanin — Dr. Sc. (Med.), Senior Research Associate, Department of Chemotherapy No. 2 of the N.N. Trapeznikov Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology; 23, Kashirskoe road, Moscow, 115478, Russian Federation; Head of the Chemotherapy Service, Moscow Clinical Research Center "Kommunarka"; 8, Sosensky stan, Sosenskoye village Kommunarka, Moscow, 108814, Russian Federation; Scientific Consultant, N.I. Pirogov National Medical and Surgical Center; 70, Nizhnyaya Pervomayskaya str., Moscow, 105203, Russian Federation; ORCID iD 0000-0001-5615-7806.
Sergey L. Gutorov — Dr. Sc. (Med.), Leading Research Associate, Department of Chemotherapy No. 4 of the N.N. Trapeznikov Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology; 23, Kashirskoe road, Moscow, 115478, Russian Federation; ORCID iD 0000-0001-5912-1155.
Sergey A. Tjulandin — Dr. Sc. (Med.), Chief Scientific Associate, Department of Chemotherapy No. 2 of the N.N. Trapeznikov Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology; 23, Kashirskoe road, Moscow, 115478, Russian Federation; ORCID iD 0000-0001-9807-2229.
Contact information: Alexey A. Rumyantsev, e-mail: alexeymma@gmail.com.
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 15.03.2022.
Revised 07.04.2022.
Accepted 04.05.2022.
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