A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma.

Rubinstein, Maria M.; Caird, Imogen; Zhou, Qin; Iasonos, Alexia; Friedman, Claire F.; Cadoo, Karen A.; Konner, Jason; O’Cearbhaill, Roisin E.; Tew, William P.; Zamarin, Dmitriy; Grisham, Rachel N.; Kyi, Chrisann; Soldan, Krysten; Lichtman, Stuart M.; Ligresti, Louise; Schweber, Sarah J.; Singh, Jasmeet; Troso-Sandoval, Tiffany A.; Aghajanian, Carol; Makker, Vicky

doi:10.1200/jco.2019.37.15_suppl.5582

Cited by 27 publications

(21 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[46][47][48] The interim results of an ongoing phase II study of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) versus durvalumab alone in recurrent endometrial cancer previously treated with platinum-based therapy were reported for 56 enrolled patients. 49 Observed ORRs were modest for both arms (14.8% of patients treated with durvalumab monotherapy and 11.1% of patients treated with combination durvalumab with tremelimumab). Additional early-phase trials are evaluating the combination of nivolumab with ipilimumab (anti-CTLA-4; NCT03508570 and NCT02982486) therapy in advanced endometrial cancer.…”

Section: Combination Immunotherapymentioning

confidence: 87%

A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer

Green

Feinberg

Makker

2020

American Society of Clinical Oncology Educational Book

Self Cite

View full text Add to dashboard Cite

Approximately 30% of primary endometrial cancers are microsatellite instability high/hypermutated (MSI-H), and 13% to 30% of recurrent endometrial cancers are MSI-H or mismatch repair deficient (dMMR). Given the presence of immune dysregulation in endometrial cancer as described, immune checkpoint blockade (ICB) has been explored as a therapeutic mechanism, both as monotherapy and in combination with cytotoxic chemotherapy, other immunotherapy, or targeted agents. In MSI-H or dMMR advanced endometrial cancers, PD-1 inhibitors dostarlimab and pembrolizumab have shown response rates of 49% and 57%, respectively, whereas PD-L1 inhibitors avelumab and durvalumab have shown response rates of 27% and 43%, respectively. In microsatellite stable (MSS) or PD-L1–positive advanced endometrial cancers, modest activity of PD-1 inhibitors nivolumab and dostarlimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab has been seen, with response rates ranging from 3% to 23%. Based on substantial activity in a phase Ib/II study, the U.S. Food and Drug Administration (FDA) granted lenvatinib and pembrolizumab combination therapy accelerated approval in 2019 for the treatment of advanced endometrial cancer that is not MSI-H or dMMR and has progressed following prior therapy. Although these developments have been highly impactful, a more robust understanding of the molecular and immunologic drivers of response and resistance will be critical to optimally design next-generation studies in endometrial cancer.

show abstract

Section: Combination Immunotherapymentioning

confidence: 87%

A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer

Green

Feinberg

Makker

2020

American Society of Clinical Oncology Educational Book

Self Cite

View full text Add to dashboard Cite

show abstract

“…The included studies were 14 phase I/II clinical trials and 1 randomized phase III trial ( 19 – 33 ). No phase IV trial was found.…”

Section: Resultsmentioning

confidence: 99%

How Immunotherapy Modified the Therapeutic Scenario of Endometrial Cancer: A Systematic Review

Maiorano

Maiorano²,

Cormio³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundEndometrial cancer (EC) represents the sixth most common female tumor. In the advanced setting, the prognosis is dismal with limited treatment options. Platinum-based chemotherapy represents the actual standard of care in first-line chemotherapy, but no standard second-line chemotherapy is approved, with less than 1/4 of patients responding to second-line chemotherapy. In the last 10 years, immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many solid tumors.MethodsThe review was conducted according to the PRISMA guidelines. We searched EMBASE, MEDLINE, Cochrane Database, and conference abstracts from international societies, up to November 2021. Clinical trials employing ICIs in advanced EC, written in English, were included. Reviews, letters, and commentaries were excluded. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety (number and grade of treatment-related adverse events [TRAEs]) were evaluated.Results15 studies, for a total of 1,627 patients, were included: 14 non-randomized phase I/II trials and 1 randomized phase III trial. Anti-PD1 (pembrolizumab, nivolumab, dostarlimab) and anti-PD-L1 agents (avelumab, atezolizumab, durvalumab) were administered as single agents; pembrolizumab and nivolumab were combined with the tyrosine-kinase inhibitors (TKI) lenvatinib and cabozantinib, respectively; and durvalumab was associated with anti-CTLA4 tremelimumab. 4 studies selected only MSI patients. Single agents determined an ORR from 26.7% to 58% among MSI patients, from 3% to 26.7% among MSS patients. DCR ranged from 53.5% to 88.9% in MSI, 31.4% to 35.2% in MSS patients. The combination of TKI and ICIs determined 32% to 63.6% of ORR in all-comers, 32%–36.2% in MSS patients. 54.2% to 76% of patients developed TRAEs. The combination of ICIs and TKI achieved a higher toxicity rate than single agents (≥G3 TRAEs 88.9%).ConclusionICIs represent an effective option for pretreated advanced EC patients with a tolerable profile. Given the encouraging results in MSI patients, every woman diagnosed with EC should be investigated for MS status. In MSS women, the combination of ICIs and TKI is more effective than monotherapy, notwithstanding safety concerns. PD-L1 cannot predict ICI response, whereas other biomarkers such as MSI and tumor mutational burden seem more accurate. Ongoing randomized trials will further clarify the role of these therapeutic options.Systematic Review RegistrationPROSPERO, CRD42021293538.

show abstract

“…CTLA-4 is an immune regulator expressed on regulatory T cells that prevents binding of CD28 and inhibits activation of cytotoxic T cells, which offers a second pathway to activate immune response to tumor cells ( Di Tucci et al, 2019 ). At a planned interim analysis, durvalumab alone and combined with tremelimumab produced modest responses (ORR 14.8% and 11.1%, respectively) in MSS and MSI-H patients ( Rubinstein et al, 2019 ). Phase III trials are summarized in Table 6 ( ClinicalTrials.gov ).…”

Section: Emerging Agents and Clinical Trialsmentioning

confidence: 99%

“…Durvalumab is also being studied in combination with the CTLA-4 inhibitor tremelimumab ( Rubinstein et al, 2019 ). CTLA-4 is an immune regulator expressed on regulatory T cells that prevents binding of CD28 and inhibits activation of cytotoxic T cells, which offers a second pathway to activate immune response to tumor cells ( Di Tucci et al, 2019 ).…”

Section: Emerging Agents and Clinical Trialsmentioning

confidence: 99%

Emerging Treatment Options for Advanced or Recurrent Endometrial Cancer

Halla¹

2022

JADPRO

View full text Add to dashboard Cite

Endometrial cancer is the most common cancer of the female reproductive organs. The American Cancer Society estimates that there will be over 65,950 new cases diagnosed in 2022. According to the National Comprehensive Cancer Network (NCCN) Guidelines, response rates in the front-line setting are approximately 40% to 62%. Prior to the recent U.S. Food and Drug Administration (FDA) approvals of immunotherapy, there had been no standard of care for women after failing front-line carboplatin and paclitaxel. In May 2017, the FDA approved single-agent pembrolizumab in microsatellite instability high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer patients following failure of systemic therapy. Then, in September 2019, the FDA approved pembrolizumab and lenvatinib for women who are not MSI-H or are MMR-proficient. This approval was based on KEYNOTE-146 and Study 111. Among 94 non–MSI-H women, 80% of those treated with pembrolizumab and lenvatinib had tumor shrinkage, and 38.3% had objective response by RECIST 1.1 as assessed by an independent radiology committee. The median duration of response was not reached, with 69% being progression free at 6 months. Grade 3/4 treatment-related adverse events (AEs) occurring in > 20%, including fatigue, hypertension, and gastrointestinal AEs. With supportive care, early identification, and intervention, the side effect profile was manageable, with only 21% discontinuing treatment due to AEs.

show abstract

A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma.

Cited by 27 publications

References 0 publications

A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer

A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer

How Immunotherapy Modified the Therapeutic Scenario of Endometrial Cancer: A Systematic Review

Emerging Treatment Options for Advanced or Recurrent Endometrial Cancer

Contact Info

Product

Resources

About