Advances in immunotherapy for cervical cancer: recent developments and future directions.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
There is an unmet need for novel therapies to improve clinical outcomes for patients with locally advanced, recurrent, or metastatic cervical cancer. Most cases of cervical cancer are driven by infection with human papillomavirus (HPV), which uses multiple mechanisms to avoid immune surveillance. Several classes of agents have been developed that seek to activate the immune system in order to overcome this resistance and improve treatment outcomes. These include immune checkpoint inhibitors, therapeutic vaccines, engineered T cells, and antibody-drug conjugates. Here, we review the immune landscape of cervical cancer and the growing clinical data regarding the use of immunotherapy. Checkpoint inhibitors are the best studied treatments, with encouraging phase II studies available in the definitive setting and recently published phase III data defining a new standard of care for patients with recurrent or metastatic disease. Vaccines and engineered T cells are generally in earlier phases of development but use unique mechanisms of immune activation. It is possible that combination of immunotherapy, with either conventional systemic therapy or multiple immunomodulatory agents, may provide further benefit. We also discuss possible synergies between immunotherapy and radiation therapy, which is frequently used in the management of cervical cancer. Ultimately, immunotherapy represents an emerging treatment option for patients with cervical cancer. It is an appropriate component of first-line treatment in the recurrent or metastatic setting and may soon be incorporated into definitive management of locally advanced disease.
10.1136/ijgc-2021-002492
Meta-analysis of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.
European journal of obstetrics, gynecology, and reproductive biology
BACKGROUND:Neither improvements in surgical techniques and methods nor advances in radiotherapy equipment and techniques have significantly improved cervical cancer survival rates for quite some time. AIM:By comparing the effectiveness of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer, this study aimed to explore effective treatment methods for locally advanced cervical cancer, and provide a theoretical basis to guide clinical practice. METHODS:A search of PubMed, Embase, Scopus, Web of Science and Cochrane databases was undertaken to identify randomized controlled trials on the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer, where the intervention in the experimental group was neoadjuvant chemotherapy. Based on the inclusion and exclusion criteria, the studies were evaluated for quality according to the Cochrane Quality Rating Scale. Baseline information, intervention information and outcome indicators of the included studies were extracted. Meta-analysis was performed using RevMan 5.4. RESULTS:Significant differences in overall survival [relative risk (RR) 1.63, 95 % confidence interval (CI) 0.69-2.57; p = 0.0007] and complete remission rate (RR 0.37, 95 % CI -0.49 to 1.23; p = 0.041) were found between the two groups. Heterogeneity of the objective response rate showed p < 0.0001 and I = 99 % (I = 99 > 50 % and p > 0.1 for the Q-test suggested strong heterogeneity). The fixed effects model was chosen for the integration statistic [standardized mean difference (SMD) 0.81, 95 % CI -0.21 to 1.83; p = 0.12]; the difference was not significant (p > 0.05). Heterogeneity of the adverse effects of neoadjuvant chemotherapy showed p < 0.0001 and I = 98 % (I = 98 %>50 % and p > 0.1 for the Q-test suggested strong heterogeneity). The fixed effects model was chosen for the integration statistic (SMD -0.023, 95 % CI -0.95 to 0.49; p = 0.53); the difference was not significant (p > 0.05). CONCLUSIONS:The use of neoadjuvant chemotherapy for the treatment of locally advanced cervical cancer improved the objective response rate and the complete remission rate of patients, but failed to improve overall survival and adverse effects.
10.1016/j.ejogrb.2024.04.023
Advances in immunotherapy in cervical cancer.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
Cervical cancer represents a major public health problem, being the fourth most common cancer in incidence and mortality in women worldwide. Patients with recurrent, persistent, or metastatic disease unsuitable for curative therapeutic approaches have a dismal prognosis. Until recently, these patients were only candidates for cisplatin-based chemotherapy plus bevacizumab. However, the introduction of immune checkpoint inhibitors has revolutionized the treatment of this disease, achieving historical overall survival improvements in both the post-platinum and front-line settings. Interestingly, the clinical development of immunotherapy in cervical cancer is currently advancing to the locally advanced setting, although preliminary efficacy outcomes in this setting have been disappointing so far. Moreover, promising data are emerging from early-phase trials on novel immunotherapy approaches, such as human papillomavirus therapeutic vaccines and adoptive cell therapy. This review summarizes the main clinical trials carried out in the field of immunotherapy in the last several years.
10.1136/ijgc-2022-003758
Recent breakthroughs in the management of locally advanced and recurrent/metastatic cervical cancer.
Journal of gynecologic oncology
Cervical cancer continues to be a global threat affecting individuals in resource poor communities disproportionately. The treatment paradigm for this disease is ever evolving with recent innovations propelling oncologic outcomes to a new frontier offering survival benefits for patients struggling with locally advanced disease and metastatic/recurrent carcinoma. Immunologic checkpoint inhibitors and anti-body drug conjugates represent two novel drug classes that have demonstrable activity in this disease, particularly in the first-line and second-line treatment paradigm for recurrence. The tolerability of these novel medicines and associated durable responses underscore regulatory approval by the U.S. Food and Drug Administrations and their implementation in clinic.
10.3802/jgo.2024.35.e30
Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: Review of the Literature and Perspectives of Clinical Research.
Gadducci Angiolo,Cosio Stefania
Anticancer research
Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is standard treatment for locally advanced cervical cancer. Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative approach, especially for patients with stage Ib2-IIb disease. This review analyzes the most commonly used combination regimens in this clinical setting and the randomized trials comparing chemo-surgery versus definitive radiotherapy or CCRT. The combination of paclitaxel plus ifosfamide plus cisplatin (TIP regimen) obtained the highest rates of optimal pathological response, associated with elevated hematological toxicity. In a recent phase II study, a dose-dense regimen consisting of weekly paclitaxel plus carboplatin for 9 cycles has achieved optimal pathological response rates similar to those of TIP with better toxicity profile. Further studies are strongly warranted to better define the optimal regimen for the patients selected to receive NACT followed by radical surgery.
10.21873/anticanres.14485
Promising predictive molecular biomarkers for cervical cancer (Review).
International journal of molecular medicine
Cervical cancer (CC) constitutes a serious public health problem. Vaccination and screening programs have notably reduced the incidence of CC worldwide by >80%; however, the mortality rate in low‑income countries remains high. The staging of CC is a determining factor in therapeutic strategies: The clinical management of early stages of CC includes surgery and/or radiotherapy, whereas radiotherapy and/or concurrent chemotherapy are the recommended therapeutic strategies for locally advanced CC. The histopathological characteristics of tumors can effectively serve as prognostic markers of radiotherapy response; however, the efficacy rate of radiotherapy may significantly differ among cancer patients. Failure of radiotherapy is commonly associated with a higher risk of recurrence, persistence and metastasis; therefore, radioresistance remains the most important and unresolved clinical problem. This condition highlights the importance of precision medicine in searching for possible predictive biomarkers to timely identify patients at risk of treatment response failure and provide tailored therapeutic strategies according to genetic and epigenetic characteristics. The present review aimed to summarize the evidence that supports the role of several proteins, methylation markers and non‑coding RNAs as potential predictive biomarkers for CC.
10.3892/ijmm.2024.5374
Advances in management of locally advanced cervical cancer.
The Indian journal of medical research
Globally, cervical cancer has the fourth highest cancer incidence and mortality in women. Cervical cancer is unique because it has effective prevention, screening, and treatment options. This review discusses the current cervical cancer advances with a focus on locally advanced cervical cancer. Topics discussed include diagnostic imaging principles, surgical management with adjuvant therapy and definitive concurrent chemoradiotherapy. Emphasis is given on current advances and future research directions in radiation therapy (RT) with an emphasis on three-dimensional brachytherapy, intensity-modulated RT, image-guided RT, proton RT and hyperthermia.
10.4103/ijmr.IJMR_1047_20
Radiotherapy of cervical cancer.
Chargari C,Peignaux K,Escande A,Renard S,Lafond C,Petit A,Lam Cham Kee D,Durdux C,Haie-Méder C
Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique
External beam radiotherapy and brachytherapy are major treatments in the management of cervical cancer. For early-stage tumours with local risk factors, brachytherapy is a preoperative option. Postoperative radiotherapy is indicated according to histopathological criteria. For advanced local tumours, chemoradiation is the standard treatment, followed by brachytherapy boost, which is not optional. We present the update of the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for cervical cancer.
10.1016/j.canrad.2021.11.009
Global challenges of radiotherapy for the treatment of locally advanced cervical cancer.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
Cervical cancer represents a significant portion of the global cancer burden for women, with low- and middle-income countries carrying the bulk of this burden. Additionally, underserved populations in countries with sufficient resources may have a higher incidence of cervical cancer and poorer outcomes. Concurrent chemoradiotherapy is the standard-of-care treatment for locally advanced cervical cancer, which includes patients with stage IB3 to IVA disease, and it is effective for many patients; however, cervical cancer-related mortality remains high. The critical nature of cervical cancer treatment is underscored by the recent launch of the World Health Organization global initiative to accelerate the elimination of cervical cancer using a triple-intervention strategy of increased vaccination, screening, and treatment. The initiative calls for 90% of all patients diagnosed with cervical cancer to receive the appropriate treatment, but to reach this global goal there are significant barriers related to radiotherapy that must be addressed. We discuss and review evidence of the lack of adherence to guideline-recommended treatment, brachytherapy underutilization, limited access to radiotherapy in low- and middle-income countries, as well as regional limitations within high-income countries, as the major barriers to radiotherapy treatment for locally advanced cervical cancer. We further review ways these barriers are currently being addressed and, in some cases, make additional recommendations to address these issues. Finally, despite receiving recommended treatments, many patients with locally advanced cervical cancer have a poor prognosis. With effective administration of current standards of care, the global community will be able to shift focus to advancing treatment efficacy for these patients. We review several types of therapies under clinical investigation that are additions to concurrent chemoradiotherapy, including immune checkpoint inhibitors, antiangiogenic agents, DNA repair inhibitors, human papillomavirus vaccines, and radiosensitizing nanoparticles.
10.1136/ijgc-2021-003001