Durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial cancer or endometrial carcinosarcoma: A randomized open-label phase 2 study Journal Article
| Authors: | Rubinstein, M. M.; Doria, E. R.; Konner, J.; Lichtman, S.; Zhou, Q.; Iasonos, A.; Sarasohn, D.; Troso-Sandoval, T.; Friedman, C.; O'Cearbhaill, R.; Cadoo, K.; Kyi, C.; Cohen, S.; Soldan, K.; Billinson, E.; Caird, I.; Jang, D.; Eid, K.; Shah, P.; Guillen, J.; Aghajanian, C.; Zamarin, D.; Makker, V. |
| Article Title: | Durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial cancer or endometrial carcinosarcoma: A randomized open-label phase 2 study |
| 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. © 2022 The Authors |
| Keywords: | adult; controlled study; aged; major clinical study; constipation; fatigue; histopathology; diarrhea; drug efficacy; monotherapy; side effect; comparative study; endometrial cancer; endometrium carcinoma; endometrium cancer; ticilimumab; progression free survival; pain; phase 2 clinical trial; anemia; nausea; randomized controlled trial; creatinine; creatinine blood level; abdominal pain; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; dyspnea; hyperglycemia; hypomagnesemia; pneumonia; pruritus; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; hyperkalemia; hypoalbuminemia; hypokalemia; hyponatremia; mismatch repair; colitis; open study; alkaline phosphatase blood level; leukocyte count; amylase blood level; triacylglycerol lipase blood level; lymphocyte count; amylase; platelet count; hypocalcemia; triacylglycerol lipase; adrenal insufficiency; phase 2; myositis; tremelimumab; international normalized ratio; overall response rate; myocarditis; body weight loss; body weight disorder; activated partial thromboplastin time; human; female; article; durvalumab; endometrial carcinosarcoma |
| Journal Title: | Gynecologic Oncology |
| Volume: | 169 |
| ISSN: | 10956859 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2023-02-01 |
| Start Page: | 64 |
| End Page: | 69 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2022.11.028 |
| PROVIDER: | scopus |
| PUBMED: | 36512912 |
| PMCID: | PMC9925401 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Maria M. Rubinstein -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work