Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial

Schmid, Peter; Yuen, Kobe C.; Gillessen, Silke; Kadel, Edward E.; Rathkopf, Dana E.; Matsubara, Nobuaki; Drake, Charles G.; Fizazi, Karim; Piulats, Josep M.; Wysocki, Piotr J.; Buchschacher, Gary L.; Alekseev, Boris; Mellado, Begoña; Karaszewska, Bogusława; Doss, Jennifer F.; Rasuo, Grozdana; Datye, Asim; Mariathasan, Sanjeev; Williams, Patrick; Sweeney, Christopher J.

doi:10.1038/s41591-021-01600-6

Cited by 131 publications

(114 citation statements)

References 60 publications

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“…The phase III IMbassador 250 trial was the first study to investigate an immunotherapy combination with atezolizumab plus enzalutamide vs. enzalutamide alone in 759 mCRPC patients who progressed on abiraterone and were ineligible for or refused a taxane regimen [ 37 ]. This study did not meet the primary endpoint of improved overall survival in unselected patients (stratified HR 1.12, 95% CI 0.91–1.37, p = 0.28).…”

Section: Immune Checkpoint Inhibitors In Castration-resistant Prostat...mentioning

confidence: 99%

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Rebuzzi

Rescigno

Catalano

et al. 2022

Cancers

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In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs.

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Section: Immune Checkpoint Inhibitors In Castration-resistant Prostat...mentioning

confidence: 99%

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Rebuzzi

Rescigno

Catalano

et al. 2022

Cancers

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“…In turn, these activate a cGAS/STING-mediated interferon response [ 36 ]. However, the inconsistency surrounding clinical outcomes in patients bearing cancers with DDR alterations and treated with immune checkpoint inhibitors questions its relevance as a biomarker [ 37 , 38 ].…”

Section: Immune Response and The Role Of The Microenvironment In Pros...mentioning

confidence: 99%

“…In the IMbassador250 phase 3 clinical trial, a combination of PD-L1 inhibitor atezolizumab and enzalutamide was compared to enzalutamide alone in patients with mCRPC who had progressed on abiraterone and docetaxel or were not candidates for a taxane regimen (NCT03016312). The combination of atezolizumab and enzalutamid did not show an OS improvement (15.2 months (95% CI: 14.0, 17.0) vs. enzalutamide alone (16.6 months (95% CI: 14.7, 18.4), requiring early termination of the study [ 38 , 141 ]. In line with previous findings, low effector T cell and macrophage signatures, as well as reduced MHC class I and immune checkpoint signatures were observed in the majority of patients.…”

Section: Immunotherapeutic Treatment Approachesmentioning

confidence: 99%

“…This is of such interest because loss of PTEN activity is known to be associated with an immunosuppressive milieu (see above). The addition of atezolizumab could potentially reverse this [ 38 ].…”

Section: Immunotherapeutic Treatment Approachesmentioning

confidence: 99%

“…A perceived setback was the phase 3 results on atezolizumab and enzalutamide showing no OS benefit for the “‘intention to treat” population, and thus requiring early termination of the trial. Nonetheless, important findings on potential biomarkers show that there are PCa patients who will benefit from immunotherapy [ 38 ]. In addition, long-term analyses of ipilimumab have recently demonstrated two to three times higher survival rates at 3 years, despite an initially negative result of the trial.…”

Section: Future Directionsmentioning

confidence: 99%

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Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

Amsberg

Alsdorf

Karagiannis

et al. 2022

IJMS

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Immunotherapeutic treatment approaches are now an integral part of the treatment of many solid tumors. However, attempts to integrate immunotherapy into the treatment of prostate cancer have been disappointing so far. This is due to a highly immunosuppressive, “cold” tumor microenvironment, which is characterized, for example, by the absence of cytotoxic T cells, an increased number of myeloid-derived suppressor cells or regulatory T cells, a decreased number of tumor antigens, or a defect in antigen presentation. The consequence is a reduced efficacy of many established immunotherapeutic treatments such as checkpoint inhibitors. However, a growing understanding of the underlying mechanisms of tumor–immune system interactions raises hopes that immunotherapeutic strategies can be optimized in the future. The aim of this review is to provide an overview of the current status and future directions of immunotherapy development in prostate cancer. Background information on immune response and tumor microenvironment will help to better understand current therapeutic strategies under preclinical and clinical development.

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Recent Progress on Nanomaterial‐Facilitated Electrochemical Strategies for Cancer Diagnosis

Yuan

Lin

Liu

et al. 2023

Adv Healthcare Materials

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Cancer is a malignant disease that endangers human life, especially owing to its high fatality rate; therefore, rapid and accurate early screening is needed to effectively improve the survival rate. Compared with traditional cancer detection methods, electrochemical biosensors that recognize cancer biomarkers in blood have the advantages of low invasiveness, fast diagnosis, and low cost. However, there is always a trade‐off between sensitivity and selectivity, which limits the detection of trace amounts of biomarkers produced in the early stages. To address this issue, an increasing number of nanomaterials with simultaneous improvements in both sensitivity and selectivity have recently been reported. In this review, different categories of state‐of‐the‐art electrochemical biosensors and their operating principles are introduced, and their respective advantages and disadvantages are described. Furthermore, the review discusses the existing detection strategies and performance of nanomaterial‐based cancer biosensors for biomarker recognition, providing overall guidance for the material selection of different biomarkers. Finally, the main challenges involving existing electrochemical cancer biosensors are evaluated to present the future development prospects of nanomaterials and detection strategies.

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Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial

Cited by 131 publications

References 60 publications

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

Recent Progress on Nanomaterial‐Facilitated Electrochemical Strategies for Cancer Diagnosis

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