Cervical cancer - Emerging treatments

Novel antibody-drug conjugates

Several novel antibody-drug conjugates in development show promise against targets such as trophoblast cell surface antigen 2 (Trop-2), B7-H4, nectin cell adhesion molecule 4 (Nectin-4), and the AXL receptor. Sacituzumab govitecan (a Trop-2 targeted conjugate) and bulumtatug fuvedotin (a Nectin-4 targeted conjugate) have undergone phase 1 and 2 trials, and further trials are in progress.[223][224][225]

Novel agents targeted against PIK3CA mutations

PIK3CA mutations are present in up to 36% of advanced or recurrent tumours.[226] In a first-in-human phase Ia study, alpelisib, an oral phosphatidylinositol 3-kinase (PI3K)-alfa selective inhibitor, demonstrated a tolerable safety profile and preliminary activity in patients with PIK3CA-altered solid tumours, including cervical cancer.[227]

Axalimogene filolisbac

Axalimogene filolisbac (a live attenuated Listeria monocytogenes-based immunotherapy that generates T cells against human papillomavirus E7-transformed cells) has shown promise in early clinical trials in patients with persistent, recurrent, or metastatic cervical cancer.[228][229][230][231] The US Food and Drug Administration (FDA) has granted fast-track designation to axalimogene filolisbac for adjuvant therapy of high-risk, locally advanced cervical cancer. A European marketing application for axalimogene filolisbac for cervical cancer was withdrawn in July 2018 due to a lack of adequate data to support the application, rather than for safety reasons.

Cadonilimab

Combination therapy, targeting both programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), has the potential to augment treatment effect. The PD-1/CTLA-4 bi-specific antibody, cadonilimab, has been approved for use in patients with relapsed or metastatic cervical cancer in China.[232] One phase 3 trial of cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer demonstrated improved progression-free survival and overall survival compared with platinum-based chemotherapy with or without bevacizumab. The median progression-free survival for the cadonilimab group was 12.7 months versus 8.1 months for the placebo group. The median overall survival was not reached for the cadonilimab group (median follow-up of 25.6 months) compared with 22.8 months for the placebo group.[233]

Adoptive T-cell therapy with tumour-infiltrating lymphocytes

Preliminary results from a phase 2 study suggest that adoptive T-cell therapy with tumour-infiltrating lymphocytes (TIL) selected for human papillomavirus E6- and E7-oncogene reactivity (HPV-TIL) can induce durable, complete regression of metastatic cervical cancer.[234] The FDA has granted breakthrough therapy designation to autologous TIL immunotherapy LN-145 for the treatment of recurrent, metastatic, or persistent cervical cancer.

Neoadjuvant and adjuvant chemotherapy

Meta-analysis suggests that intensive neoadjuvant chemotherapy plus surgery is associated with some impact on survival compared with surgery alone. However, methodological challenges to the analysis and the lack of clinical codification has prevented it becoming a standard approach.[235] Neoadjuvant chemotherapy plus surgery does not appear to offer a survival advantage over chemoradiotherapy for patients with stage IB2-IIB cervical cancer.[236][237] Adjuvant chemotherapy is being investigated in international clinical trials for patients with high-risk or advanced stage disease. [ ]