This review aims to characterize the most recent targeted and biologic therapies currently being evaluated in the treatment of advanced cervical cancer.Ģ. Current Standard Therapy for Recurrent Cervical Cancer Novel therapies have been developed and are currently being studied in clinical trials to increase options for management in this patient population. However, in the recurrent, progressive, or metastatic setting, there remains an absence of curative therapies. In addition to screening, the development of highly effective vaccinations targeting high risk HPV genotypes, are predicted to be effective at preventing the vast majority of cervical cancer in immunized women in the future. The high-risk HPV E6 and E7 oncoproteins bind natural tumor suppressors – p53 and Rb – to propagate malignant transformation. Persistent HPV infection has been recognized as a prerequisite for the development of invasive cervical cancer for over twenty years. įortunately, the understanding of cervical cancer biology and oncogenesis has evolved. Moreover, nearly three decades passed before the FDA approved a new, targeted therapy for cervical cancer, bevacizumab, to be utilized in addition to a traditional platinum chemotherapy doublet. Indeed, platinum-based chemotherapy in combination with radiation was deemed highly active in the treatment of advanced cervical cancer in late 1990s. Unfortunately, this number has largely been stagnant since 1999, and while screening practices have demonstrated that cervical cancer is largely preventable, this trend suggests a recent lack of progress in the treatment of advanced and/or recurrent disease. Nonetheless, over 4000 women are estimated to die from cervical cancer in the United States in 2019. In the United States, improved screening augmented by implementation of HPV testing in the last two decades has led to a decreased incidence of cervical cancer. Finally, an additional targeted approach being pursued are PARP inhibitors (rucaparib and olaparib are both in phase II) based on earlier study results.Ĭervical cancer is both the fourth most commonly diagnosed and the deadliest cancer in women worldwide. Additional checkpoint inhibitors including nivolumab, durvalumab, atezolizumab, and camrelizumab are in different stages of clinical development for the disease. Another anti-PD1 antibody, cemiplimab also shows potential in this setting, either as monotherapy or combined with radiotherapy, and it is currently being evaluated in a phase III trial. In June 2018, the US FDA approved the anti-PD1 antibody pembrolizumab for recurrent or metastatic cervical cancer with PD-L1 expression that progressed after one or more lines of chemotherapy. As the majority of cervical cancers have a viral etiology, which impairs the immune system, immunotherapy using checkpoint inhibitors and other agents, appears to be a promising approach. In 2014, the anti-VEGF antibody bevacizumab was approved in combination with chemotherapy based on the results of the phase III GOG-240 study. Few effective treatment options exist for persistent, recurrent, or metastatic cervical cancer. Survival decreases markedly for both locally advanced and metastatic disease, and both are associated with a higher risk of recurrence. Early stage cervical cancer has an excellent long-term prognosis, with 5-year survival for localized disease being >90%. While screening programs and HPV vaccination have decreased the incidence of cervical cancer, still over 13,000 cases occur in the United States annually.
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