The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer

Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)

“…Given the immunologic dysfunction that prevents viral clearance in women who develop cervical cancer, immunologic-based therapies are promising, and currently undergoing investigation is a Listeria monocytogenes -based HPV 16 E7 therapeutic vaccine (ADXS-HPV), autologous T-cell therapy, and the anti-programmed cell death 1 (PD-1) immunomodulators, nivolumab, and pembrolizumab. 28,29 Signal transduction pathways relevant to cervical carcinogenesis that can be targeted include the PI3K/Akt/mTOR pathway, homologous recombination deficiency pathways through which to exploit synthetic lethality, and the Notch binary cell-fate decision pathway. 28,30 Finally, adenoviral-directed gene therapy to reconstitute wild type p53 function or suicide genes, as well as the identification and targeting of cervical cancer stem cells may also represent viable therapeutic options in the future.…”

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

“…Bevacizumab and doublet chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) were adopted as first-line (1L) standard-ofcare therapy for recurrent or metastatic cervical cancer in the past 5 years (4-6). However, nearly all patients relapse after 1L treatment, and single-institution experiences indicate that the percentage of patients who receive a second-line (2L) therapy varies (30%-70%) as many patients die before receiving treatment (7,8).Available 2Lþ therapies for recurrent or metastatic cervical cancer are characterized by low response rates (5,6). Before adoption of bevacizumab plus doublet chemotherapy in 1L, therapies administered in the 2Lþ setting reported response rates in the range of 4.5% to 15%, with median survival of <8 months (9-15).…”

“…Bevacizumab and doublet chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) were adopted as first-line (1L) standard-ofcare therapy for recurrent or metastatic cervical cancer in the past 5 years (4-6). However, nearly all patients relapse after 1L treatment, and single-institution experiences indicate that the percentage of patients who receive a second-line (2L) therapy varies (30%-70%) as many patients die before receiving treatment (7,8).…”

“…Introduction treatment (7), suggesting that prior vascular endothelial growth factor inhibition may negatively impact subsequent treatment response. Data in the third-line setting are further limited, with approximately 60% of patients not receiving third-line treatment and, when treated, response rates of 3% (8). Recently, pembrolizumab (anti-programmed death 1) was granted accelerated approval in the United States for the 2Lþ treatment of patients with programmed death-ligand 1 (PD-L1)positive (combined positive score !1%) recurrent or metastatic cervical cancer (16).…”

Synchronous Cervical Adenocarcinoma and Ovarian Serous Adenocarcinoma—A Case Report and Literature Review

“…These data were also sustained by the study conducted between 2004 and 2014 at the Royal Marsden Hospital, which demonstrated that second line therapy in the setting of advanced and recurrent cervical cancer is associated with poor rates of response; moreover, the authors underlined the necessity of exploring the effectiveness of novel targeted agents and immunotherapy in such cases. Data related in this study are particularly important due to the fact that different and aggressive biological subtypes such as clear cell, adenocarcinoma, and even neuroendocrine uterine cervix carcinomas have been included [23]. As for the cases diagnosed in early stages of the disease, fertility sparing surgery should not be taken into consideration, due to the more aggressive biological behavior of this histopathological subtype.…”