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Updated: May 30, 2025
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Can we learn from failures? A systematic review of phase III trials in platinum-resistant ovarian cancer
Federica Martorana1, Giuliana Pavone1, Cristiana Sessa2
1Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; Humanitas Istituto Clinico Catanese, Misterbianco, Catania, Italy.
Objective:
This systematic review analyzed phase III trials in platinum-resistant ovarian cancer to understand their poor outcomes and guide future trials.
Methods:
A systematic review adhering to PRISMA guidelines was conducted. PubMed/Medline, Cochrane Library CENTRAL, and EMBASE were searched for randomized phase III trials (2010-January 2024) involving patients with platinum-resistant ovarian cancer.
Results:
Fifteen studies (5,468 patients) were included. Platinum resistance was defined by the interval between last platinum administration and recurrence/progression. Heterogeneity existed in defining platinum-refractory patients. Experimental arms included chemotherapy (4 trials), immune checkpoint inhibitors, anti-angiogenic agents, targeted agents, or antibody-drug conjugates (2 trials each), and others (3 trials). Control arms consistently used single-agent chemotherapy (paclitaxel, gemcitabine, pegylated liposomal doxorubicin, or topotecan). Only four trials had biomarker-selected populations. Most trials (except TRINOVA1, AURELIA, and MIRASOL) showed no progression-free survival benefit. Only MIRASOL had statistically significant overall survival improvement.
Conclusion:
Negative outcomes likely stem from various factors, including inconsistent platinum resistance definitions, inadequate control arm benchmarks, and suboptimal biomarker use. A deeper understanding of tumor biology and its integration into trial design is crucial to enhance drug development in this patient population, aiming for improved efficacy while preserving quality of life.
Insights
Future clinical trials for platinum-resistant ovarian cancer need improved designs. Current phase III trials show poor outcomes due to inconsistent definitions and limited biomarker use, with only one trial demonstrating survival benefit.
Area of Science:
- Oncology
- Clinical Trials
- Ovarian Cancer Research
Background:
- Platinum-resistant ovarian cancer (PROC) presents significant treatment challenges with poor patient outcomes.
- Phase III trials in PROC have yielded limited success, necessitating a review of trial design and execution.
Purpose of the Study:
- To systematically review phase III clinical trials in PROC to identify factors contributing to poor outcomes.
- To provide insights for optimizing future trial designs in PROC.
Main Methods:
- A systematic review following PRISMA guidelines was performed.
- Searched major databases (PubMed/Medline, CENTRAL, EMBASE) for randomized phase III trials from 2010 to January 2024.
- Included 15 trials involving 5,468 patients with PROC.
Main Results:
- Heterogeneity was observed in defining platinum resistance and platinum-refractory status.
- Experimental therapies included chemotherapy, immune checkpoint inhibitors, anti-angiogenic agents, targeted agents, and antibody-drug conjugates.
- Most trials did not show progression-free survival benefit; only MIRASOL demonstrated a statistically significant overall survival improvement.
- Biomarker selection was limited to only four trials.
Conclusions:
- Suboptimal outcomes in PROC trials are linked to inconsistent definitions, inadequate control arms, and poor biomarker utilization.
- Integrating a deeper understanding of tumor biology into trial design is essential for advancing drug development.
- Future strategies must focus on improving efficacy and patient quality of life in PROC treatment.
