Phase II study of olaparib + durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC)

Drew, Yvette; Kaufman, Bella; Banerjee, Susana; Lortholary, Alain; Hong, Sook Hee; Park, Y.H.; Zimmermann, Stefan; Roxburgh, Patricia; Ferguson, Michelle; Álvarez, Ricardo H.; Domchek, Susan M.; Gresty, Christopher; Angell, Helen K.; Ros, Vidalba Rocher; Meyer, Keith; Lanasa, Mark C.; Herbolsheimer, Pia; Jonge, Maja de

doi:10.1093/annonc/mdz253.016

Cited by 81 publications

(58 citation statements)

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“…Taken together, the available preclinical and translational data strongly support combining PARP inhibition and ICB, and based on these data, a number of clinical trials are currently ongoing (Table 1). Up to now, data from three different PARP inhibitor/anti-PD-1/L1 combinations are available: olaparib/ durvalumab (98,99), niraparib/pembrolizumab (100,101), and BGB-A317/BGB-290 (102). Both of the first combinations were well tolerated, with toxicities in line with those observed for the relevant agents in monotherapy settings.…”

Section: Combining Parp Inhibition and Checkpoint Blockadementioning

confidence: 88%

Development of PARP and Immune-Checkpoint Inhibitor Combinations

2018

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PARP inhibitors drive increased DNA damage, particularly in tumors with existing defects in DNA repair. This damage not only promotes immune priming through a range of molecular mechanisms, but also leads to adaptive upregulation of programmed death ligand 1 (PD-L1) expression. In this context, PARP inhibition and programmed cell death 1 (PD-1)/PD-L1-targeting antibodies represent a rationale combination. In this review, we detail the basic and translational science underpinning this promising new combination, summarize available clinical data, and discuss the key questions that remain to be addressed during future development. Cancer Res; 78(24); 6717-25. Ó2018 AACR.

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Section: Combining Parp Inhibition and Checkpoint Blockadementioning

confidence: 88%

Development of PARP and Immune-Checkpoint Inhibitor Combinations

2018

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“…The ORR was 71.9% (with 7 CRs), with a median duration of response (DOR) of 10.2 months and a 28-week DCR of 65.6%; median PFS was 11.1 months and median OS was not reached, with 87.0% of patients alive at 24 months [ 38 ].…”

Section: Role Of Immune Check Point Inhibitors In Ovarian Cancer Tmentioning

confidence: 99%

Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors

Nero

Ciccarone

Pietragalla

et al. 2021

Cancers

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Ovarian cancer treatment strategy is mainly based on three pillars: cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. The latter in the last decade has provided a remarkable improvement in progression free patients and, hopefully, in overall survival. In particular, poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors exploit BRCA 1/2 mutations and DNA damage response deficiencies, which are believed to concern up to 50% of high grade epithelial ovarian cancer cases. While these agents have an established role in ovarian cancer treatment strategy in BRCA mutated and homologous recombination deficient patients, an appropriate predictive molecular test to select patients is lacking in clinical practice. At the same time, the impressive results of immunotherapy in other malignancies, have opened the space for the introduction of immune-stimulatory drugs in ovarian cancer. Despite immune checkpoint inhibitors as a monotherapy bringing only modest efficacy when assessed in pretreated ovarian cancer patients, the combination with chemotherapy, anti-angiogenetics, PARP inhibitors, and radiotherapy is believed to warrant further investigation. We reviewed literature evidence on PARP inhibitors and immunotherapy in ovarian cancer treatment.

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“…Based on the efficacy results from a double-blind, placebo-controlled, phase III trial, atezolizumab plus carboplatin and etoposide have been FDA approved for first-line treatment of adult patients with extensive-stage small cell lung cancer [ 34 ]. A combination of poly(ADP-ribose) polymerase (PARP) inhibitors with PD-L1 inhibitor (olaparib + durvalumab) has also been tested, with results showing improved efficacies of combination treatments in germline BRCA-mutated platinum-sensitive relapsed ovarian cancer patients [ 35 ] and patients with relapsed gastric cancer [ 36 ] in the MEDIOLA study. Interestingly, some chemotherapies have been shown to increase the expression of PD-1/PD-L1, hence contributing to immunosuppression and poor responses to chemotherapies alone [ 37 , 38 , 39 ].…”

Section: Types Of Immunotherapy: Their Combinations and Limitationmentioning

confidence: 99%

Immunotherapies and Combination Strategies for Immuno-Oncology

Barbari

Fontaine

Parajuli

et al. 2020

IJMS

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The advent of novel immunotherapies in the treatment of cancers has dramatically changed the landscape of the oncology field. Recent developments in checkpoint inhibition therapies, tumor-infiltrating lymphocyte therapies, chimeric antigen receptor T cell therapies, and cancer vaccines have shown immense promise for significant advancements in cancer treatments. Immunotherapies act on distinct steps of immune response to augment the body’s natural ability to recognize, target, and destroy cancerous cells. Combination treatments with immunotherapies and other modalities intend to activate immune response, decrease immunosuppression, and target signaling and resistance pathways to offer a more durable, long-lasting treatment compared to traditional therapies and immunotherapies as monotherapies for cancers. This review aims to briefly describe the rationale, mechanisms of action, and clinical efficacy of common immunotherapies and highlight promising combination strategies currently approved or under clinical development. Additionally, we will discuss the benefits and limitations of these immunotherapy approaches as monotherapies as well as in combination with other treatments.

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Phase II study of olaparib + durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC)

Cited by 81 publications

References 0 publications

Development of PARP and Immune-Checkpoint Inhibitor Combinations

Development of PARP and Immune-Checkpoint Inhibitor Combinations

Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors

Immunotherapies and Combination Strategies for Immuno-Oncology

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