EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer

Oaknin, Ana; Monk, Bradley J.; Vergote, Ignace; Melo, Andréia Cristina de; Kim, Yong‐Man; Lisyanskaya, Alla S.; Samouëlian, Vanessa; Kim, Hee Seung; Gotovkin, Evgeniy A.; Damian, Fernanda; Chang, Chih‐Long; Takahashi, Shunji; Li, Jingjin; Mathias, Melissa; Fury, Matthew G.; Ivanescu, Cristina; Reaney, Matthew; LaFontaine, Patrick R.; Lowy, Israel; Harnett, James; Chen, Chieh-I; Tewari, Krishnansu S.

doi:10.1016/j.ejca.2022.03.016

Cited by 19 publications

(7 citation statements)

References 20 publications

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“…Interestingly objective responses were seen also in patients with PD-L1 expression of less than 1%. The good safety profile of cemiplimab was consistent with that previously reported for the other ICIs in other tumor types ( 14 ). Importantly, only 8.7% of patients receiving cemiplimab discontinued treatment for any grade of immune-related adverse events (irAE)s.…”

Section: Introductionsupporting

confidence: 89%

Complete and early response to cemiplimab associated to severe immune toxicity in advanced cervical cancer: a case report

Passarelli,

Pisano,

Coppola

et al. 2023

Front. Immunol.

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Cervical cancer (CC) is the second most commonly diagnosed cancer and the third leading cause of cancer death among females. The options of treatment for recurrent/advanced CC are limited and patients experiencing recurrence after first line platinum-based chemotherapy have a poor prognosis. In this context, immune checkpoint inhibitors (ICI)s antagonizing PD-1 and programmed death-ligand 1 (PD-L1) have profoundly changed the treatment scenario and outcomes in CC in the first or subsequent lines both as monotherapies or in combination with chemotherapy or other ICIs. Herein, we report the clinical case of a 74-year-old woman with metastatic CC with negative tumor PD-L1 expression who having disease progression after first-line of systemic treatment with platinum, thus undergoing to anti-PD-1 namely cemiplimab. The patient achieved a surprising, fast and complete metabolic response to cemiplimab immediately discontinued after only two cycles due to the onset of rare and severe immune-related adverse events (irAE)s such cardiovascular toxicity and hypertransaminasemia. Despite this, thirteen months later, the patient remains disease-free despite cemiplimab was withdrawn.

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Section: Introductionsupporting

confidence: 89%

Complete and early response to cemiplimab associated to severe immune toxicity in advanced cervical cancer: a case report

Passarelli,

Pisano,

Coppola

et al. 2023

Front. Immunol.

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“…Although PD‐L1 is expressed in 34.4%−96% of CCa tissues, the objective response rate was only 18% (95% CI, 11 to 28) among cemiplimab‐treated patients with PD‐L1 expression in ≥1% of cells and merely 11% (95% CI, 4 to 25) among those with PD‐L1 expression in <1% of cells. [ 12 ] The results of these trials suggest that a small subset of PD‐L1‐positive patients benefit from PD‐1/PD‐L1 inhibitor therapy, underscoring the need for combinatorial approaches involving blockade of the PD‐L1 pathway for cancer therapy. Moreover, these observations emphasize the importance of developing strategies to modulate the TIME and identifying novel therapeutic targets to improve immunotherapy outcomes.…”

Section: Introductionmentioning

confidence: 99%

NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer

Chen,

Hao,

Liu

et al. 2023

Advanced Science

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Immunotherapy has recently emerged as the predominant therapeutic approach for cervical cancer (CCa), driven by the groundbreaking clinical achievements of immune checkpoint inhibitors (ICIs), such as anti‐PD‐1/PD‐L1 antibodies. N4‐acetylcytidine (ac4C) modification, catalyzed by NAT10, is an important posttranscriptional modification of mRNA in cancers. However, its impact on immunological dysregulation and the tumor immunotherapy response in CCa remains enigmatic. Here, a significant increase in NAT10 expression in CCa tissues is initially observed that is clinically associated with poor prognosis. Subsequently, it is found that HOXC8 activated NAT10 by binding to its promoter, thereby stimulating ac4C modification of FOXP1 mRNA and enhancing its translation efficiency, eventually leading to induction of GLUT4 and KHK expression. Moreover, NAT10/ac4C/FOXP1 axis activity resulted in increased glycolysis and a continuous increase in lactic acid secretion by CCa cells. The lactic acid‐enriched tumor microenvironment (TME) further contributed to amplifying the immunosuppressive properties of tumor‐infiltrating regulatory T cells (Tregs). Impressively, NAT10 knockdown enhanced the efficacy of PD‐L1 blockade‐mediated tumor regression in vivo. Taken together, the findings revealed the oncogenic role of NAT10 in initiating crosstalk between cancer cell glycolysis and immunosuppression, which can be a target for synergistic PD‐1/PD‐L1 blockade immunotherapy in CCa.

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“…8 For the first time in years, patients with recurrent or metastatic disease who have already received one line of systemic chemotherapy now have an option for treatment that is superior to traditional chemotherapy and has a safety profile and infusion schedule that allow for an acceptable quality of life. 9 The interest in immunotherapy for this disease has led to further exploration of its use in the frontline setting: in combination with chemotherapy for patients with recurrent and/or metastatic disease and in combination with chemoradiation (CRT) for patients with locally advanced disease. The results of Keynote 826, a multicenter, randomized, double-blind, placebo-controlled trial, led to FDA approval of pembrolizumab in combination with chemotherapy, with or without bevacizumab, for patients with persistent, recurrent, or metastatic cervical cancer whose tumors expressed PD-L1 (combined positive score ≥ 1).…”

Section: Immunotherapy (Table 1)mentioning

confidence: 99%

“…In the overall trial population (including all patients, regardless of their tumor PD‐L1 status), the median overall survival was longer in the cemiplimab group than the chemotherapy group (12.0 vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56–0.84; two‐sided p < .001) 8 . For the first time in years, patients with recurrent or metastatic disease who have already received one line of systemic chemotherapy now have an option for treatment that is superior to traditional chemotherapy and has a safety profile and infusion schedule that allow for an acceptable quality of life 9 …”

Section: Immunotherapy (Table 1)mentioning

confidence: 99%

Section: Immunotherapy (Table 1 )mentioning

confidence: 99%

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Top advances of the year: Cervical cancer

Podwika

Duska

2023

Cancer

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Cervical cancer continues to affect women in the United States and throughout the world despite an effective vaccine against human papillomavirus and cancer screening programs. For the women who develop cervical cancer, surgery, radiation, and chemotherapy have been the mainstays of treatment for years. Recently, novel therapeutics have been developed that offer new treatment opportunities for women living with advanced and/or recurrent disease. Immunotherapy has become an important tool against cervical cancer with the approval of pembrolizumab in the second line for advanced or recurrent disease. Checkpoint inhibitors have recently been approved in the front line for advanced and/or recurrent disease in combination with chemotherapy, and they are being studied in the front line in combination with chemoradiation. Antibody–drug conjugates—specifically tisotumab vedotin (TV)—also have recently received Food and Drug Administration (FDA) approval, and TV is currently being studied in combination with checkpoint inhibitors and with carboplatin. Tumor‐infiltrating lymphocytes have been studied in early‐phase trials and have shown promise in small patient series. Despite these new therapies, there continue to be racial, ethnic, and socioeconomic inequities with respect to access to care, access to and participation in clinical trials, and survival in the United States as well as globally. New FDA guidance requires researchers to work to reduce disparities by including women of more diverse backgrounds in clinical trials. Finally, as progress continues to be made in the treatment of established disease, prevention through vaccination and screening remains paramount. Plain language summary The treatment of cervical cancer remains a significant problem in the United States and especially worldwide. Although early cases can be cured, cervical cancer that has spread remains difficult to treat. The past few years have seen significant advances in new therapies and combinations of therapies for women with advanced or recurrent disease. Although this is excellent news for these women, cervical cancer is a preventable disease through screening with Papanicolaou smears and vaccination with the human papillomavirus vaccine. By improving access to and acceptance of screening and vaccination, we can eradicate cervical cancer in the United States and the world.

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EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer

Cited by 19 publications

References 20 publications

Complete and early response to cemiplimab associated to severe immune toxicity in advanced cervical cancer: a case report

Complete and early response to cemiplimab associated to severe immune toxicity in advanced cervical cancer: a case report

NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer

Top advances of the year: Cervical cancer

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