A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)–only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer

Kristeleit, Rebecca; Давиденко, Ірина; Shirinkin, Vadim; El-Khouly, Fatima; Bondarenko, Igor; Goodheart, Michael J.; Gorbunova, Vera; Penning, C A; Shi, Jack G.; Liu, Xiangdong; Newton, Robert; Zhao, Yufan; Maleski, Janet; Leopold, Lance; Schilder, Russell J.

doi:10.1016/j.ygyno.2017.07.005

Cited by 85 publications

(59 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No objective responses were detected, although stable disease for ≥16 weeks was observed in 7/52 patients (106). A randomized Phase 2 study compared epacadostat versus tamoxifen treatment in 42 patients with biochemically recurrent-only epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer, where epacadostat was found to be well tolerated but showed no difference in efficacy (107). …”

Section: Discovery and Preclinical Development Of Ido1 Inhibitorsmentioning

confidence: 99%

Discovery of IDO1 Inhibitors: From Bench to Bedside

et al. 2017

View full text Add to dashboard Cite

Small molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) are emerging at the vanguard of experimental agents in oncology. Here pioneers of this new drug class provide a bench-to-bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds – indoximod, epacadostat and navoximod – that were first to be evaluated as IDO inhibitors in clinical trials. As ‘immunometabolic adjuvants’ to widen therapeutic windows, IDO inhibitors may leverage not only immuno-oncology modalities but also chemotherapy and radiotherapy as standards of care in the oncology clinic.

show abstract

Section: Discovery and Preclinical Development Of Ido1 Inhibitorsmentioning

confidence: 99%

Discovery of IDO1 Inhibitors: From Bench to Bedside

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In human patients, epacadostat monotherapy was not effective (163,164), while combined administration with PD-1 or cytotoxin T-lymphocyte-associated protein 4 (CTLA-4) inhibitors showed promising clinical activity in phase I/II studies (165)(166)(167)(168). Unfortunately, a recent trial with combined administration of epacadostat with pembrolizumab found no superiority over pembrolizumab alone (169).…”

Section: Immune Tolerance Related To Indoleamine 23-dioxygenase 1 Acmentioning

confidence: 99%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

View full text Add to dashboard Cite

Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.

show abstract

“…The National Comprehensive Cancer Network (NCCN) guidelines for OC suggest that biochemical recurrent patients may: 1) enroll in a clinical trial; 2) delay treatment until clinical relapse; 3) receive immediate platinum-based recurrence therapy; or 4) undergo best supportive care (25). Thus, several studies aimed to investigate low-toxicity agents to delay the appearance of measurable disease in these patients (26). However, no e cacy agent was con rmed until now.…”

Section: Discussionmentioning

confidence: 99%

Apatinib in treating clinical and biochemical recurrent ovarian cancer

Wang

Huang

Лонг

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Apatinib, a small molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), exerts antiangiogenic effects. Taken orally, apatinib shows clinical activity in the treatment of recurrent or platinum-resistant ovarian cancer (OC) as monotherapy or in combination with other chemotherapeutic agents. We investigated the efficacy of apatinib in recurrent OC and preliminarily evaluated the clinical activity of apatinib in biochemical-only recurrent OC patients. Results: We retrospectively analyzed clinical material of 41 recurrent patients who had received apatinib monotherapy or apatinib plus chemotherapy between June 2016 and August 2018. Apatinib was administered at a 500 mg daily dose. Response was determined according to measurable disease or serum carbohydrate antigen (CA)-125 levels. Progression-free survival (PFS) was estimated by Kaplan-Meier method. All patients were evaluable, 19 (46.34%) had biochemical relapse and 22 (53.66%) had clinical relapse. The objective response rate (ORR) and disease control rate (DCR) in the overall population were 31.71% and 78.05%, respectively. The median PFS was 7 months (95% confidence interval 5.43-8.57). In patients with biochemical relapse only, the median PFS was 6 months, with ORR of 26.32% and DCR of 89.47%. Conclusions: Apatinib is a well-tolerated and effective agent in patients with recurrent OC and has the potential to delay clinical progression in patients with asymptomatic biochemical relapse.

show abstract

A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)–only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer

Abstract: This first report of immunotherapy evaluation in biochemical-only relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found no significant difference in efficacy between epacadostat and tamoxifen. Epacadostat was generally well tolerated.

Cited by 85 publications

References 33 publications

Discovery of IDO1 Inhibitors: From Bench to Bedside

Discovery of IDO1 Inhibitors: From Bench to Bedside

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Apatinib in treating clinical and biochemical recurrent ovarian cancer

Contact Info

Product

Resources

About