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4CPS-184 Therapies in endometrial cancer with dna mismatch repair deficient or microsatellite instability: a systematic review
  1. C Moreno Ramos1,
  2. MD Gil-Sierra2,
  3. MDP Briceño-Casado2,
  4. M Reyes Malia3,
  5. E Campos Dávila4
  1. 1Servicio Andaluz De Salud, Farmacia Hospitalaria, Cádiz, Spain
  2. 2Hospital Universitario Jerez De La Frontera, Farmacia Hospitalaria, Jerez De La Frontera, Spain
  3. 3Hospital Infanta Elena, Farmacia Hospitalaria, Huelva, Spain
  4. 4Hospital De La Línea De La Concepción, Farmacia Hospitalaria, La Línea, Spain


Background and Importance Standard therapy for advanced endometrial cancer (EC) pre-treated with platinum-based chemotherapy (PCT) showed limited efficacy. DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) neoplasms are associated with increased PD-1 and PD-L1 expression. Thus, immunotherapy could play an important role in EC with dMMR/MSI-H.

Aim and Objectives To conduct a systematic review of scientific evidence on treatments for EC with dMMR/MSI-H in patients who previously received PCT.

Material and Methods A literature search in PubMed® database was performed to August 2023. Filter ‘clinical trials’ was applied with the following search strategy: [microsatellites instability OR Mismatch Repair Deficient] AND endometrial cancer. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was used in bibliographic review. Inclusion criteria: clinical trials (CTs) involving patients with dMMR, or MSI-H diagnosed with advanced and/or metastatic EC who had previously received PCT. Efficacy endpoints assessed were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Data collected: publication date, study design, stage, median patient follow-up, sample size, therapies, comparator arm and efficacy data.

Results A total of 30 search results were identified. Thirteen CTs met the inclusion criteria. These studies were published between May 2019 and February 2023. Study design: nine non-randomised phase II, two non-randomised phase I, one randomised phase III and one randomised phase Ib/II. Patients with advanced EC were included in 23.1% of CTs, with metastatic disease in 23.1% and both in 53.8%. Median follow-up ranged from six to 42.6 months. Sample size comprised 11 to 130 patients. Therapies analysed were: pembrolizumab, pembrolizumab plus lenvatinib, durvalumab, durvalumab plus tremelimumab, dostarlimab, nivolumab and avelumab. A total of 11 studies had no comparator arm. Pembrolizumab achieved the highest numerical efficacy [OS= 40.0 months (95% CI 25.3-Not Reached); PFS= 23.5 months (95% CI 10.7-NR); ORR= 58% (95% CI 37–78)]. Dostarlimab [OS= NR; PFS= 12.2 months (95% CI not available); ORR= 43.5% (95% CI 34.5–53.4)] and durvalumab [OS= NR; PFS= 8.3 months (95% CI 2.4-NR); ORR= 47% (95% CI 32–63)] presented the next best numerical efficacy. No CTs compared pembrolizumab with dostarlimab or durvalumab.

Conclusion and Relevance The greatest numerical efficacy data were achieved by pembrolizumab, followed by dostarlimab and durvalumab. Nevertheless, CTs with adequate comparisons are needed for reliable data interpretation.

Conflict of Interest No conflict of interest.

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