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Keynote 158 cervical cancer11/5/2023 10,11 At the time of writing, there is no evidence that further treatments after first line improve OS compared with best supportive care. 9 In 2014, the addition of bevacizumab to cisplatin–paclitaxel chemotherapy showed an improvement of OS, with 16.8 months in the bevacizumab chemotherapy arm compared with 13.3 months in the chemotherapy alone arm (hazard ratio, 0.77 95% confidence interval, 0.62–0.95 p=0.007), leading the bevacizumab regimen to become the new standard first-line therapy in the metastatic setting. 8 In the recurrent setting, carboplatin–paclitaxel demonstrated non-inferiority compared with cisplatin–paclitaxel doublet in patients pretreated with cisplatin. 7,8 When associated with cisplatin, paclitaxel demonstrated the same efficacy but less toxicity compared with topotecan, gemcitabine or vinorelbine. 6 Cisplatin-based chemotherapy, alone or in association with paclitaxel, represents the gold standard first-line treatment for persistent, recurrent or metastatic CC, with an overall response rate (ORR) of 13% in monotherapy and 36% in platinum-based doublet. 5 In cases of relapsed or de novo metastatic CC, the prognosis remains poor, with an overall survival (OS), at diagnosis, ranging from 5 to 16 months. 4 However, the risk of recurrence is 11–22% and 28–64% for early and locally advanced stages, respectively. 3 Early-stage disease, which consists of stages from I to IIA, can usually be managed by surgery alone whereas locally advanced stages, including stages from IIB to IVA, are usually treated by cisplatin-based chemoradiotherapy. 1 Patients diagnosed in the metastatic stage have a poor prognosis, with a 5-year survival rate of only 17%. 2 Nevertheless, the worldwide incidence of CC is still significant, with approximately 604,000 new cases per year. Thanks to the introduction of specific vaccination and screening programmes for HPV, mortality has decreased by 75% in industrial countries over the past 50 years. 1ĬC is mainly attributable to human papillomavirus (HPV) infection. 1 Indeed, worldwide 341,831 women die each year because of this disease, with a mortality rate that varies across different countries, with, for example, less than two per 100,000 in Western countries such as Australia and New Zealand to more than 22 per 100,000 in Africa. KeywordsĬervical cancer, immune checkpoint inhibitors, anti-PD1, anti-PD-L1, pembrolizumab Article:Ĭervical cancer (CC) remains one of the most frequent cancers in women, representing the fourth cause of neoplasia in women in terms of incidence, and has a high lethality rate. We also aim to address some outstanding questions and discuss the next steps in immunotherapy for CC. This article reviews the promising outcomes of the KEYNOTE-826 phase III trial, which evaluates the addition of pembrolizumab to chemotherapy in patients with PD-L1-positive disease and recurrent, persistent or metastatic cancer of the cervix, leading to an improvement of progression-free survival and overall survival. The pathogen-induced nature of the disease, the involvement of genes regulating the immune response and the high grade of immune infiltration provide the rationale to evaluate anti-programmed death-(ligand)1 (PD-1) immune checkpoint inhibitors in CC. Most cases of cervical carcinoma are related to HPV infection. Cervical cancer (CC) still has a high incidence despite screening programmes and access to human papillomavirus (HPV) vaccination, with a poor prognosis in the advanced setting.
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