An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in germline  BRCA -mutated ( gBRCA m) platinum-sensitive relapsed (PSR) ovarian cancer (OC)

Drew, Yvette; Jonge, Maja de; Hong, Sook Hee; Park, Y.H.; Wolfer, Anita; Brown, Jennifer R.; Ferguson, Michelle; Gore, Martin; Álvarez, Ricardo H.; Gresty, Christopher; Angell, Helen K.; Meyer, Keith; Learoyd, Maria; Tang, Minhong; Lanasa, Mark C.; Herbolsheimer, Pia; Domchek, Susan M.

doi:10.1016/j.ygyno.2018.04.555

Cited by 115 publications

(98 citation statements)

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“…To our knowledge to date, limited clinical data are available from 3 active PARP inhibitor and PD-1 and/or PD-L1 blockade combination trials demonstrating early clinical activity in subsets of patients with recurrent ovarian cancer. A 72% response rate (RR) has been reported for durvalumab and olaparib in patients with germline BRCA-mutant, platinum-sensitive ovarian cancer 28 ; a 25% RR has been reported for niraparib and pembrolizumab in patients with platinum-resistant ovarian cancer 29 ; and a 14% RR has been reported for durvalumab and olaparib in heavily pretreated patients with ovarian cancer, predominantly composed of those with platinum-resistant BRCA wildtype disease. 30 In support, several phase 3 randomized trials of multipathway modulation (immune checkpoint inhibitor with or without PARP inhibition with or without VEGF inhibition) currently are being investigated in the frontline setting for ovarian cancer.…”

Section: Novel Combinations Targeting the Tumor And Tumor Microenviromentioning

confidence: 99%

New strategies in ovarian cancer treatment

Lee

Minasian

Kohn

2019

Cancer

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Insights from basic science dissecting carcinogenesis in the fallopian tube and ovary have led to a deeper understanding of the origin, molecular characteristics, and types of ovarian cancers. This logically then has led to the development of novel approaches to treat ovarian cancer. Increasingly, novel agents are being developed to target the different growth pathways. The identification of molecular markers associated with different histopathologies has resulted in newer clinical trial designs to capture both clinical and translational endpoints. Unique molecular characteristics in DNA damage and repair pathways and unique cell surface markers have driven new drug development, yielding promise for both patients with platinum-sensitive and platinum-resistant ovarian cancers. Specific examples described include the histology-selective mutations, such as ARID1A in clear cell and endometrioid ovarian cancers; the rationale for using cell cycle checkpoint inhibitors when there already is a p53-mediated loss of cell cycle checkpoint regulation or combinations of agents that will both induce neoantigen formation and unleash immune modulators; and techniques to enhance the therapeutic delivery of known agents. A systematic and thoughtful approach to combining agents in clinical trials is needed so that irrespective of the trial outcomes, the results inform both clinical and translational endpoints.

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Section: Novel Combinations Targeting the Tumor And Tumor Microenviromentioning

confidence: 99%

New strategies in ovarian cancer treatment

Lee

Minasian

Kohn

2019

Cancer

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“…Some preclinical models have demonstrated the upregulation of PD-L1 after exposure to PARPi. 28 The same combination was studied in a population of 32 patients, with the majority of patients with platinum-resistant disease recurrences (83%) achieving an ORR of 14%. 26,27 This biological observation has been tested clinically in 3 phase 2 studies.…”

Section: Combination Of Cpis and Parpimentioning

confidence: 99%

“…The Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors (MEDIOLA) trial included 32 patients with germ-line BRCA-mutant and platinumsensitive, recurrent ovarian, fallopian tube, or peritoneal cancer who were treated with durvalumab and olaparib and achieved a significant ORR of 63% (19% CR rate) from a chemotherapy-free regimen. 28 The same combination was studied in a population of 32 patients, with the majority of patients with platinum-resistant disease recurrences (83%) achieving an ORR of 14%. 29 Finally, the Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer (TOPACIO)/KEYNOTE-162 trial included 60 pretreated patients with recurrent ovarian, fallopian tube, or peritoneal cancer, 48% of whom had platinum-resistant disease, 27% of whom had platinumrefractory disease, and 24% of whom were not eligible for further platinum treatment.…”

Section: Combination Of Cpis and Parpimentioning

confidence: 99%

Immunotherapy with checkpoint inhibitors in patients with ovarian cancer: Still promising?

González-Martín

Sánchez-Lorenzo

2019

Cancer

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Despite advances in surgery and chemotherapy and the integration of antivascular endothelial growth factor therapy as well as poly(adenosine diphosphate-ribose) polymerase inhibitors into daily clinical practice, epithelial ovarian cancer remains the leading cause of death from gynecological cancer. The incorporation of new therapies with the potential to achieve long-term disease remission is a clear need for patients with ovarian cancer. Immunotherapy with checkpoint inhibitors (CPIs) (antiprogrammed cell death protein 1 [anti-PD-1] or antiprogrammed death-ligand 1 [anti-PD-L1]) has been adopted in several malignancies based on improvements shown with regard to progression-free survival and in particular overall survival. Although there is a solid rationale for the use of CPIs in patients with ovarian cancer, to our knowledge the clinical data presented to date are not very convincing. This article reviews the current data regarding CPIs in patients with ovarian cancer along with the future directions and designs of clinical trials aiming to overcome the low efficacy of CPIs in these individuals. Cancer 2019;125:4616-4622.

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“…The second trial (MEDIOLA) enrolled patients with recurrent platinum-sensitive ovarian cancer with germline BRCA mutations only in second- or later line therapy 46. Treatment started with a 4-week run-in of olaparib monotherapy and then concurrent treatment with PARPi and durvalumab.…”

Section: Immunological Checkpointsmentioning

confidence: 99%

Immunotherapy in ovarian cancer: fake news or the real deal?

Marth¹,

Wieser

Tsibulak

et al. 2019

Int J Gynecol Cancer

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Cancer immunotherapy has emerged as one of the most promising approaches in oncology, and comprises the activation of the immune system to induce tumor immune surveillance or to reverse the tumor immune escape. Different therapeutic strategies for ovarian carcinoma have evolved over the years. Already 30 years ago, the first clinical studies focused on modulating the tumor cytokine network with special attention to interferon-mediated immune responses. With the exploration of specific tumor antigens such as NY-ESO-1, which is expressed in ovarian carcinoma and other malignancies, the development of therapeutic cancer vaccines has been pursued initiating the era of personalized anti-cancer medicine. Almost at the same time, the adoptive transfer of genetically modified autologous tumor-reactive T-cells occurred, but response rates in ovarian carcinoma were disappointing. Today, probably the most promising therapeutic approach in this context is the blockade of immune checkpoints, such as programed cell death protein 1 (PD-1) and one of its ligands (PD-L1) or cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4), which has demonstrated impressive response rates in malignant melanoma and non-small cell lung cancer. Despite increasing availability of treatment approaches that target tumor immune surveillance in ovarian carcinoma, selecting patient groups that particularly benefit from these treatment modalities is clinically challenging as predictive biomarkers are lacking. Here, we summarize different immunotherapy approaches in ovarian cancer and discuss why immunotherapy in ovarian cancer is still in its infancy.

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An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in germline BRCA -mutated ( gBRCA m) platinum-sensitive relapsed (PSR) ovarian cancer (OC)

Cited by 115 publications

References 0 publications

New strategies in ovarian cancer treatment

New strategies in ovarian cancer treatment

Immunotherapy with checkpoint inhibitors in patients with ovarian cancer: Still promising?

Immunotherapy in ovarian cancer: fake news or the real deal?

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