Durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial cancer or endometrial carcinosarcoma: A randomized open-label phase 2 study.
Gynecol Oncol
; 169: 64-69, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36512912
ABSTRACT
INTRODUCTION:
Our understanding of the biologic heterogeneity of endometrial cancer has improved, but which patients benefit from single-agent versus combination immune checkpoint blockade remains unclear.METHODS:
We conducted a single-center, randomized, open-label, phase 2 study of durvalumab 1500 mg (Arm 1) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks (Arm 2) in patients with endometrial carcinoma. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS) at 24 weeks. Patients were stratified by mismatch repair (MMR) status and carcinosarcoma histology. Using a Simon two-stage minimax design, we determined 40 patients per arm would provide 90% power and Type 1 error of 10%.RESULTS:
Eighty-two patients were enrolled; 77 were evaluable for toxicity (Arm 1 38, Arm 2 39) and 75 evaluable for efficacy (Arm 1 37, Arm 2 38). Patient were stratified by MMR status (Arm 1 5, Arm 2 4 were MMR-deficient). The ORR in Arm 1 was 10.8% (one-sided 90% CI 4.8-100%); the ORR in Arm 2 was 5.3% (one-sided 90% CI 1.4-100%). Since the primary endpoint of ORR was not met, 24-week PFS was not compared to historical controls per protocol specification. No new safety signals were identified.CONCLUSIONS:
In these patients with predominantly MMR-proficient endometrial cancer, there was limited response with single-agent and combined immune checkpoint blockade. The pre-specified efficacy thresholds were not met for further evaluation. A deeper understanding of potential mechanisms of resistance to immunotherapy in MMR-proficient endometrial cancer is needed for the development of novel therapeutic approaches.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
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Inibidores de Checkpoint Imunológico
Tipo de estudo:
Clinical_trials
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Guideline
/
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Gynecol Oncol
Ano de publicação:
2023
Tipo de documento:
Article