Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study

Pujade-Lauraine, Éric; Fujiwara, Keiichi; Ledermann, Jonathan A.; Oza, Amit M.; Kristeleit, Rebecca; Ray‐Coquard, Isabelle; Richardson, Gary; Sessa, Cristiana; Yonemori, Kan; Banerjee, Susana; Léary, Alexandra; Tinker, Anna V.; Jung, Kyung Hae; Mądry, Radosław; Park, Soo‐Jin; Anderson, Charles; Zohren, Fabian; Stewart, Ross; Wei, Caimiao; Dychter, Samuel S.; Monk, Bradley J.

doi:10.1016/s1470-2045(21)00216-3

Cited by 195 publications

(209 citation statements)

References 22 publications

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“…Evidence of the immunostimulatory effects of chemotherapy has thus provided a rationale for its combination with ICB therapy with a view to further enhance cytotoxic T-cell activity and improve clinical outcomes. Regrettably, phase III trials failed to demonstrate any survival benefit when combining the anti-PDL-1 avelumab with pegylated liposomal doxorubicin chemotherapy in recurrent OC [ 41 ]. Another trial was terminated due to lack of efficacy when combining ICB with carboplatin and paclitaxel in untreated, advanced OC (NCT02718417) [ 42 ].…”

Section: Immunoregulatory Pathways Within the Tmementioning

confidence: 99%

Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment

Johnson

Cummings

Thangavelu

et al. 2021

Cancers

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A lack of explicit early clinical signs and effective screening measures mean that ovarian cancer (OC) often presents as advanced, incurable disease. While conventional treatment combines maximal cytoreductive surgery and platinum-based chemotherapy, patients frequently develop chemoresistance and disease recurrence. The clinical application of immune checkpoint blockade (ICB) aims to restore anti-cancer T-cell function in the tumour microenvironment (TME). Disappointingly, even though tumour infiltrating lymphocytes are associated with superior survival in OC, ICB has offered limited therapeutic benefits. Herein, we discuss specific TME features that prevent ICB from reaching its full potential, focussing in particular on the challenges created by immune, genomic and metabolic alterations. We explore both recent and current therapeutic strategies aiming to overcome these hurdles, including the synergistic effect of combination treatments with immune-based strategies and review the status quo of current clinical trials aiming to maximise the success of immunotherapy in OC.

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Section: Immunoregulatory Pathways Within the Tmementioning

confidence: 99%

Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment

Johnson

Cummings

Thangavelu

et al. 2021

Cancers

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“…Immunotherapy, the second treatment modality, is aimed at restoring the ability of the patient’s immune system to eradicate a tumor and largely focused on reactivation of T lymphocytes ( Rodriguez et al, 2018 ). Although HGSC tumors show high frequencies of functionally exhausted T cells, with high levels of immune checkpoint proteins, responses to immunotherapy for HGSC have not shown clinical benefit ( Rodriguez et al, 2018 ; Kandalaft et al, 2019 ; Zamarin et al, 2020 ; Pujade-Lauraine et al, 2021 ; Webb et al., 2015 ). A deeper understanding of the cell types within the HGSC immune microenvironment could assist in identifying mechanistic biomarkers to select patients likely to derive the most benefit from immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

High-grade serous ovarian tumor cells modulate NK cell function to create an immune-tolerant microenvironment

et al. 2021

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High-grade serous ovarian tumor cells modulate NK cell function to create an immune-tolerant microenvironment Graphical abstract Highlights d Decidual-like NK cells correlate with tumor cell abundance in tubo-ovarian HGSC d Combinatorial NK receptor ligand expression levels differ across tumor compartments d NK cells acquire CD9 from HGSC tumor cells via trogocytosis d CD9 suppresses anti-tumor cytokine production and cytotoxicity in NK-92 cells

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“…In a subgroup analysis, patients with PD-L1 and CD8 expression on tumor cells, and those without primary platinum resistance, tended to gain more from combination therapy. Unfortunately, this also did not reach statistical significance However, this draws attention to the need for a better selection of patients for further research [ 63 ]. The NINJA trial compared nivolumab versus gemcitabine (GEM) or pegylated liposomal doxorubicin (PLD) treatment for patients with platinum-resistant (advanced or recurrent) ovarian cancer.…”

Section: Immunotherapy In Ovarian Cancermentioning

confidence: 99%

Immunotherapy of Ovarian Cancer with Particular Emphasis on the PD-1/PDL-1 as Target Points

Świderska

Kozłowski

Kwiatkowski

et al. 2021

Cancers

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Ovarian cancer is one of the most fatal cancers in women worldwide. Cytoreductive surgery combined with platinum-based chemotherapy has been the current first-line treatment standard. Nevertheless, ovarian cancer appears to have a high recurrence rate and mortality. Immunological processes play a significant role in tumorigenesis. The production of ligands for checkpoint receptors can be a very effective, and undesirable, immunosuppressive mechanism for cancers. The CTLA-4 protein, as well as the PD-1 receptor and its PD-L1 ligand, are among the better-known components of the control points. The aim of this paper was to review current research on immunotherapy in the treatment of ovarian cancer. The authors specifically considered immune checkpoints molecules such as PD-1/PDL-1 as targets for immunotherapy. We found that immune checkpoint-inhibitor therapy does not have an improved prognosis in ovarian cancer; although early trials showed that a combination of anti-PD-1/PD-L1 therapy with targeted therapy might have the potential to improve responses and outcomes in selected patients. However, we must wait for the final results of the trials. It seems important to identify a group of patients who could benefit significantly from treatment with immune checkpoints inhibitors. However, despite numerous trials, ICIs have not become part of routine clinical practice for the treatment of ovarian cancer.

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Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study

Cited by 195 publications

References 22 publications

Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment

Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment

High-grade serous ovarian tumor cells modulate NK cell function to create an immune-tolerant microenvironment

Immunotherapy of Ovarian Cancer with Particular Emphasis on the PD-1/PDL-1 as Target Points

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