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Immunotherapy in advanced endometrial cancer with microsatellite instability: A systematic review
Cristina Moreno-Ramos1, Manuel David Gil-Sierra2, María Del Pilar Briceño-Casado2
1Subdirección de Farmacia, Servicios Centrales de Extremadura, Mérida, Spain.
Background:
Endometrial cancer with microsatellite instability (MSI) involves 30% of diagnosed cases. There are some uncertainty about second-line treatment, after platinum-based first-line treatment. The aim of this study was to perform a systematic review on the scientific evidence of immunotherapies for endometrial cancer with MSI.
Methods:
PubMed and Embase databases were searched up to May 28, 2024. We included clinical trials about patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H) diagnosed with advanced and/or metastatic endometrial cancer who had previously received platinum-based chemotherapy. Clinical trials with a dMMR or MSI-H population size of less than 10 patients were discarded. Efficacy results in overall survival, progression-free survival and objective response rate were used to determine the most interesting drugs. A safety analysis of therapies was developed.
Results:
Fifty-four studies were found in a systematic search. Fourteen clinical trials were selected. The following drugs were evaluated: pembrolizumab monotherapy, pembrolizumab plus lenvatinib, durvalumab, durvalumab-tremelimumab combination, dostarlimab, nivolumab and avelumab. The greatest numerical efficacy effect was achieved by pembrolizumab, followed by pembrolizumab in combination with lenvatinib. The most common adverse events were fatigue and gastrointestinal disorders.
Conclusion:
The efficacy of pembrolizumab and pembrolizumab-lenvatinib regimen appears promising. However, studies with larger sample size, longer follow-up and comparative design with subgroup analysis based on differences in microsatellite repair mechanisms are needed for proper therapeutic positioning.
Insights
Immunotherapies show promise for advanced endometrial cancer with microsatellite instability (MSI). Pembrolizumab, alone or with lenvatinib, demonstrated the greatest efficacy in a systematic review of clinical trials for MSI-H/dMMR patients. Further research is needed for definitive therapeutic positioning.
Area of Science:
- Oncology
- Immunotherapy
- Gynecologic Oncology
Background:
- Microsatellite instability (MSI) is present in 30% of endometrial cancer cases.
- Optimal second-line treatment following platinum-based chemotherapy remains uncertain for MSI endometrial cancer.
Purpose of the Study:
- To systematically review the scientific evidence on immunotherapies as second-line treatment for endometrial cancer with MSI.
- To evaluate the efficacy and safety of various immunotherapeutic agents in this patient population.
Main Methods:
- A systematic search of PubMed and Embase databases was conducted up to May 28, 2024.
- Included were clinical trials of advanced/metastatic endometrial cancer patients with dMMR/MSI-H who received prior platinum-based chemotherapy (minimum 10 patients).
- Efficacy (overall survival, progression-free survival, objective response rate) and safety data were analyzed.
Main Results:
- Fourteen clinical trials involving pembrolizumab, pembrolizumab plus lenvatinib, durvalumab, durvalumab-tremelimumab, dostarlimab, nivolumab, and avelumab were selected.
- Pembrolizumab, followed by the combination of pembrolizumab and lenvatinib, showed the greatest numerical efficacy.
- Fatigue and gastrointestinal disorders were the most frequently reported adverse events.
Conclusions:
- The combination of pembrolizumab and lenvatinib shows promising efficacy for endometrial cancer with MSI.
- Larger, comparative studies with longer follow-up and subgroup analyses are necessary for definitive therapeutic guidance.
