VP4-2021: EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9: Interim analysis of phase III trial of cemiplimab vs. investigator's choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical carcinoma

Tewari, Krishnansu S.; Monk, Bradley J.; Vergote, Ignace; Miller, Austin; Melo, Andréia Cristina de; Kim, H.S.; Kim, Y.M.; Lisyanskaya, Alla Sergeevna; Samouëlian, Vanessa; Lorusso, Domenica; Damian, Fernanda; Cl, Chang; Gotovkin, E.A.; Takahashi, Shunji; Ramone, Daniella; Pikiel, Joanna; Li, J.; Mathias, Melissa; Fury, Matthew G.; Oaknin, Ana

doi:10.1016/j.annonc.2021.04.009

Cited by 37 publications

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“…These data indicate the potential benefit of inhibiting PD-L1 but also the challenges in providing benefit to patients whose tumors do not express PD-L1. Promising results have also been reported recently with cemiplimab in second-line or later settings in patients with persistent, recurrent, or metastatic cervical cancer ( 39 ).…”

Section: Current Treatment For Persistent Recurrent or Metastatic Cer...mentioning

confidence: 81%

“…Recently reported data from the phase 3 EMPOWER trial of cemiplimab, an anti–PD-1 agent, in patients with recurrent, persistent, or metastatic cervical cancer who had disease progression with prior platinum-based chemotherapy have for the first time showed that anti–PD-(L)1 therapy can produce better outcomes than chemotherapy in this setting ( 39 ). This trial evaluated cemiplimab monotherapy vs investigator choice of single-agent chemotherapy; all patients had received one prior line of therapy, and 40.8% had received more than one prior therapy.…”

Section: Future Treatment Options In Cervical Cancer Targeting Hpv-me...mentioning

confidence: 99%

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The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-β and PD-L1 Pathways

et al. 2022

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Cervical cancer is one of the most common and lethal cancers among women worldwide. Treatment options are limited in patients with persistent, recurrent, or metastatic cervical cancer, with <20% of women living >5 years. Persistent human papillomavirus (HPV) infection has been implicated in almost all cases of cervical cancer. HPV infection not only causes normal cervical cells to transform into cancer cells, but also creates an immunosuppressive environment for cancer cells to evade the immune system. Recent clinical trials of drugs targeting the PD-(L)1 pathway have demonstrated improvement in overall survival in patients with cervical cancer, but only 20% to 30% of patients show overall survival benefit beyond 2 years, and resistance to these treatments remains common. Therefore, novel treatment strategies targeting HPV infection–associated factors are currently being evaluated in clinical trials. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody that blocks PD-L1. Early clinical trials of bintrafusp alfa have shown promising results in patients with advanced cervical cancer.

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Section: Current Treatment For Persistent Recurrent or Metastatic Cer...mentioning

confidence: 81%

Section: Future Treatment Options In Cervical Cancer Targeting Hpv-me...mentioning

confidence: 99%

The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-β and PD-L1 Pathways

et al. 2022

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“…More importantly, overall survival was improved with a hazard ratio of 0.69 (95% CI 0.56–0.84; p < 0.001) in favor of cemiplimab. Median overall survival was 12.0 versus 8.5 months 21 . While PD-L1 targeted therapies are a welcome advance in treatment for these often-young patients, there is a high unmet need for novel therapies with more efficacy and broader applicability.…”

Section: Discussionmentioning

confidence: 95%

Pre-clinical activity of the oral DNA-PK inhibitor, peposertib (M3814), combined with radiation in xenograft models of cervical cancer

Gordhandas

Manning‐Geist

Henson

et al. 2022

Sci Rep

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DNA-dependent protein kinase (DNA-PK) plays a crucial role in repair of DNA double-strand breaks by facilitating non-homologous end-joining. Inhibitors of DNA-PK have the potential to block DNA repair and enhance DNA-damaging agents. Peposertib (M3814) is a DNA-PK inhibitor that has shown preclinical activity in combination with DNA-damaging agents, including ionizing radiation (IR) and topoisomerase II inhibitors. Here we evaluated the activity of peposertib (M3814) in combination with radiation in a mouse xenograft model of HPV-associated cervical cancer. Athymic nude female mice with established tumors derived from HeLa cells injected into the flank were treated with vehicle alone (n = 3), IR alone (n = 4), and peposertib (M38814) in combination with IR (M3814 + IR; n = 4). While IR alone was associated with a trend towards decreased tumor volume compared with untreated, only the M3814 + IR treatment arm was associated with consistent and significant reduction in tumor burden, which correlated with higher levels of γ-H2AX in tumor cells, a marker of double-strand DNA breaks. Our data support further clinical evaluation of the combination of peposertib (M38814) and IR in cervical cancer.

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“…Recurrent or metastatic cervical cancer patients who had progressed after platinum-based CHT were treated with either cemiplimab or the investigators’ choice of CHT. An interim analysis of 608 patients clearly favored cemiplimab treatment with regards to OS (12.0 vs. 8.5 months, p < 0.001), PFS and ORR [ 98 ]. In summary, the current evidence on ICI for cervical cancer is encouraging; however, ORR for ICI monotherapy in patients progressing after platinum-based chemotherapy is still low.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Immunotherapy for Cervical Cancer—A Systematic Review of Clinical Trials

Schmidt

Battista

Schmidt

et al. 2022

Cancers

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Purpose: To systematically review the current body of evidence on the efficacy and safety of immunotherapy for cervical cancer (CC). Material and Methods: Medline, the Cochrane Central Register of Controlled Trials and Web of Science were searched for prospective trials assessing immunotherapy in CC patients in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text articles in English and German reporting outcomes of survival, response rates or safety were eligible. Results: Of 4655 screened studies, 51 were included (immune checkpoint inhibitors (ICI) n=20; therapeutic vaccines n = 25; adoptive cell transfer therapy n=9). Of these, one qualified as a phase III randomized controlled trial and demonstrated increased overall survival following treatment with pembrolizumab, chemotherapy and bevacizumab. A minority of studies included a control group (n = 7) or more than 50 patients (n = 15). Overall, response rates were low to moderate. No response to ICIs was seen in PD-L1 negative patients. However, few remarkable results were achieved in heavily pretreated patients. There were no safety concerns in any of the included studies. Conclusion: Strong evidence on the efficacy of strategies to treat recurrent or metastatic cervical cancer is currently limited to pembrolizumab in combination with chemotherapy and bevacizumab, which substantiates an urgent need for large confirmatory trials on alternative immunotherapies. Overall, there is sound evidence on the safety of immunotherapy in CC.

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VP4-2021: EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9: Interim analysis of phase III trial of cemiplimab vs. investigator's choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical carcinoma

Abstract: Interim analysis of phase III trial of cemiplimab vs. investigator's choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical carcinoma

Cited by 37 publications

References 0 publications

The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-β and PD-L1 Pathways

The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-β and PD-L1 Pathways

Pre-clinical activity of the oral DNA-PK inhibitor, peposertib (M3814), combined with radiation in xenograft models of cervical cancer

Efficacy and Safety of Immunotherapy for Cervical Cancer—A Systematic Review of Clinical Trials

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