A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D

Lee, Jung‐Yun; Kim, Jae Weon; Lim, Myong Cheol; Kim, Sung Hoon; Kim, Hee Seung; Choi, Chel Hun; Yi, Ju Yeon; Park, Sang-Yoon; Kim, Byoung-Gie

doi:10.3802/jgo.2019.30.e112

Cited by 20 publications

(13 citation statements)

References 10 publications

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“… 107 The Korean Gynecologic Oncology Group has initiated a phase II study (KGOG 346) of neoadjuvant durvalumab and the CTLA-4 inhibitor tremelimumab together with chemotherapy in stage IIIC and IV ovarian cancer. 108 Patients will continue postoperatively with adjuvant chemotherapy and durvalumab and serial biopsies are incorporated in the trial design in order to study biomarkers of response.…”

Section: Immunotherapy Combinations Beyond Parp Inhibitors and Cellulmentioning

confidence: 99%

<p>Further Understanding of High-Grade Serous Ovarian Carcinogenesis: Potential Therapeutic Targets</p>

Voutsadakis¹

2020

CMAR

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High-grade serous ovarian carcinoma (HGSOC) is the most common type of ovarian cancer and the most lethal gynecologic malignancy due to advanced stage at presentation. Recent years have witnessed progress in the therapy of HGSOC with the introduction of PARP (poly-adenosine diphosphate ribose polymerase) inhibitors and the anti-angiogenic monoclonal antibody bevacizumab to the backbone of chemotherapy or as maintenance therapy after chemotherapy. The improved molecular understanding of ovarian cancer pathogenesis, which has brought these therapies into the clinic, aspires to extend the boundaries of therapies through elucidation of other molecular aspects of ovarian carcinogenesis. This accumulating knowledge has started to be translated to additional targeted therapies that are in various stages of development. These include inhibitors of the function of other proteins involved in homologous recombination deficiency (HRD), such as WEE1 kinase, ATM/ATR kinases and CDK12 inhibitors. Despite disappointing results with immune checkpoint inhibitors monotherapy, harnessing the immune system in HGSOC with combination therapies that promote antigen production and immune cell activation is an avenue being explored. This paper examines arising HGSOC therapies based on molecular understanding of pathogenesis.

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Section: Immunotherapy Combinations Beyond Parp Inhibitors and Cellulmentioning

confidence: 99%

<p>Further Understanding of High-Grade Serous Ovarian Carcinogenesis: Potential Therapeutic Targets</p>

Voutsadakis¹

2020

CMAR

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“…Böhm et al [22] suggested that NAC may enhance patients' immune responses, opening a window of opportunity for immune checkpoint inhibitors for patients with advanced-stage ovarian cancer. Based on these results, we began an ongoing clinical trial examining the benefit of combination therapy with conventional chemotherapy, anti-PD-L1, and anti-CTLA-4 to improve the chemotherapy response in NAC [23]. Patients with a low disease burden after NAC who have had a good response to chemotherapy may consider minimally invasive surgery at the time of IDS.…”

Section: Discussionmentioning

confidence: 99%

Rethinking Radical Surgery in Interval Debulking Surgery for Advanced-Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy

Lee

Nam

Kim

et al. 2020

JCM

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The aim of this study is to evaluate the effects on survival outcomes of the disease burden before interval debulking surgery (IDS), surgical complexity, and residual disease after IDS in advanced-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC). We reviewed the data of 268 epithelial ovarian cancer patients who had received three or four cycles of NAC and undergone optimal resections through IDS. The Kaplan–Meier method and Cox regression analysis were used to assess the effects of disease burden (peritoneal cancer index (PCI)), degree of complexity of surgery (surgical complexity score/s (SCS)), and extent of residual disease. In no residual disease (R0) patients, those with intermediate/high SCS had shorter progression-free survival (PFS; p = 0.001) and overall survival (OS; p = 0.001) than patients with low SCS. An analysis of a subset of patients with R0 and low PCIs showed those with intermediate/high SCS had worse PFS and OS than patients with low SCS (p = 0.049) and OS (p = 0.037). In multivariate analysis, patients with R0 as a result of intermediate/high SCS fared worse than patients whose R0 was achieved by low SCS (PFS hazard ratio (HR) 1.80, 95% CI 1.05–3.10; OS HR 5.59, 95% CI 1.70–18.39). High PCIs at the time of IDS, high SCS, and residual disease signal poor prognoses for patients treated with NAC.

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“…Durvalumab (MEDI4736) is a fully human monoclonal antibody targeting PD-L1 [ 40 ] which improved the OS of patients with advanced NSCLC [ 41 ], advanced urothelial bladder cancer [ 42 ], HNSCC progressed on platinum-based chemotherapy [ 43 ]. Several phase I and phase II studies showed efficacy in triple negative breast cancer [ 44 ] and in advanced-stage ovarian cancer in combination with tremelimumab [ 45 ] or olaparib [ 46 ]. Studies are ongoing.…”

Section: Pd-1 and Pd-l1 Inhibitors In Cancermentioning

confidence: 99%

Is There a Place for PD-1-PD-L Blockade in Acute Myeloid Leukemia?

et al. 2021

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Checkpoint inhibitors were a major breakthrough in the field of oncology. In September 2014, based on the KEYNOTE-001 study, the Food and Drug Administration (FDA) approved pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, for advanced or unresectable melanoma. Up until now, seven PD-1/PD-ligand(L)-1 inhibitors are approved in various solid cancers and hundreds of clinical studies are currently ongoing. In hematology, PD-1 inhibitors nivolumab and pembrolizumab were approved for the treatment of relapsed/refractory (R/R) classic Hodgkin lymphoma, and later pembrolizumab was approved for R/R primary mediastinal large B-cell lymphoma. In acute myeloid leukemia (AML), the combination of hypomethylating agents and PD-1/PD-L1 inhibitors has shown promising results, worth of further investigation, while other combinations or single agent therapy have disappointing results. On the other hand, rather than in first line, these therapies could be useful in the consolidation or maintenance setting, for achieving minimal residual disease negativity. Furthermore, an interesting application could be the use of PD-1/PD-L1 inhibitors in the post allogeneic hematopoietic stem cell transplantation relapse. There are several reasons why checkpoint inhibitors are not very effective in treating AML, including the characteristics of the disease (systemic, rapidly progressive, and high tumor burden disease), low mutational burden, and dysregulation of the immune system. We here review the results of PD-1/PD-L1 inhibition in AML and discuss their potential future in the management of this disease.

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A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D

Cited by 20 publications

References 10 publications

<p>Further Understanding of High-Grade Serous Ovarian Carcinogenesis: Potential Therapeutic Targets</p>

<p>Further Understanding of High-Grade Serous Ovarian Carcinogenesis: Potential Therapeutic Targets</p>

Rethinking Radical Surgery in Interval Debulking Surgery for Advanced-Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy

Is There a Place for PD-1-PD-L Blockade in Acute Myeloid Leukemia?

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