Metastatic Cervical Cancer Patients Research Articles

Addition of Bevacizumab to Chemotherapy and Its Impact on Clinical Efficacy in Cervical Cancer: A Systematic Review and Meta-Analysis

Background and Objectives: Cervical cancer is the third leading cause of cancer-related mortality in females. One of the most successful therapeutic modalities to date is suppressing vascular endothelial growth factor (VEGF)-mediated angiogenesis. Bevacizumab is a monoclonal antibody that targets VEGF-A. The outcomes for cervical cancer patients treated with bevacizumab in combination with platinum-based chemotherapy have been explored in several studies. This study aimed to assess the impact of bevacizumab on progression-free survival (PFS) and overall survival (OS) in patients with metastatic cervical cancer. Materials and Methods: This systematic review was registered in PROSPERO (CRD42023456755). Following PRISMA guidelines, a comprehensive literature search on PubMed and Google Scholar identified 28 studies meeting the inclusion criteria. The outcomes of interest were PFS and OS. The statistical analysis computed hazard ratios (HRs) with 95% confidence intervals (CIs). The study also included a subgroup analysis by cervical cancer stage. Results: The pooled analysis revealed that bevacizumab-based therapy significantly improved both PFS with HR 0.77 (95% CI: 0.58–0.96; p < 0.01; I2 = 58%) and OS with HR 0.63 (95% CI: 0.45–0.89; p < 0.01; I2 = 41%) in cervical cancer patients. Subgroup analysis by stage of cervical cancer demonstrated better efficacy of bevacizumab in metastatic stage IVB cervical cancer patients indicated by HR for PFS (0.69, 95% CI: 0.54–0.79; p < 0.01) and HR for OS (0.57, 95% CI: 0.46–0.73; p < 0.01). Conclusions: Bevacizumab exhibits a significant increase in PFS and OS, underscoring the efficacy of anti-angiogenesis therapy in cervical cancer, particularly in stage IVB metastatic cervical cancer patients.

Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers

BackgroundImmunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear. MethodsWe retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC. Clinical outcomes including tumor response and patient survival were assessed. Kaplan-Meier curves with the log-rank test were employed to compare survival data. Cox regression analysis was utilized to investigate prognostic factors. ResultsA total of 65 R/M CC patients treated with immune checkpoint inhibitors were eligible for analysis. We found that immunotherapy combined with palliative radiotherapy showed a significant positive correlation with complete response (OR = 6.31; 95 %CI: 1.74–22.91; p = 0.005). The 36-month progression-free survival (PFS) rate (73.7 % vs 33.8 %, p = 0.0048) and 36-month overall survival (OS) rate (85.7 % vs 38.7 %, p = 0.0043) were also prominently increased. We further demonstrated that patients prolonged 36-month PFS rate (69.9 % vs 15.2 %; p < 0.001) and 36-month OS rate (64.6 % vs 39.7 %; p = 0.032) when they had more than 4 cycles of immunotherapy. Meanwhile, our findings showed that patients with only recurrence had longer 36-month OS rate (77.7 % vs 44.4 % vs 40.1 %; p = 0.024) compared to those with only metastasis and both. We also observed that patients with squamous carcinoma had higher 2-year PFS rate (57.9 % vs 14.6 %; p = 0.042) than those with other pathological subtypes (adenocarcinoma, adenosquamous carcinoma and neuroendocrine carcinoma). ConclusionsThe combination of immunotherapy and palliative radiotherapy increased complete response rates and improved survivals in recurrent or metastatic cervical cancer patients.

723P A phase II study of cadonilimab plus chemotherapy in persistent recurrent/ metastatic cervical cancer patients who failed previous immuno/chemotherapy

723P A phase II study of cadonilimab plus chemotherapy in persistent recurrent/ metastatic cervical cancer patients who failed previous immuno/chemotherapy

Clinical efficacy and safety of cadonilimab immunotherapy in patients with advanced cervical cancer: A retrospective study.

e17519 Background: For patients with recurrent or metastatic cervical cancer, especially those with negative PD-L1 expression, there is a lack of effective treatment and often indicate poor prognosis. A multicenter retrospective study was conducted to evaluate the safety and antitumor activity of cadonilimab in recurrent or metastatic cervical cancer patients. Methods: Patients with metastatic or recurrent cervical cancer, who underwent treatment of cadonilimab at Shenzhen People’s Hospital and Huazhong University of Science and Technology Union Shenzhen Hospital. All patients received immunotherapy of cadonilimab at a dose of 10mg/kg of body weight with/without the combination of chemotherapy/bevacizumab/ radiotherapy. Cadonilimab were repeated every 3 weeks until disease progression or intolerable toxicity. Antitumor activity and safety were assessed in all patients. Results: Since July 2022 to November 2023. A total of 18 patients (Figo stage IB1-IIIC) with recurrent/metastatic cervical cancer, 3 patients with newly diagnosed advanced cervical cancer (Figo stage IVB stage) were included. With a median follow-up of 7.0 months (IQR 1.9–15.4), the number of treatment cycles for cadonilimab ranged from 3 to 17 cycles, with a median of 7 cycles. 6 patients with PD-L1-positive expression, 5 patients with negative expression, and 10 patients were unknown. 8 patients combined of chemotherapy, 7 patients received cadonilimab monotherapy, 4 patients combined of chemotherapy and bevacizumab, 1 patient combined of bevacizumab, 1 patients combined of chemotherapy, bevacizumab and radiotherapy . 2 patients with newly diagnosed advanced disease and 2 patients with recurrent cervical cancer achieved complete response (CR), 11 patients with achieved partial response(PR) and 1 patients were in stable disease(SD). The objective response rate (ORR) was 71.4% (15 of 21 patients). The ORR of patients with the PD-L1-negative expression was 80% (4 of 5 patients).Grade 3–4 treatment-related adverse events occurred in 7 (33.3%) of 21 patients, the most frequent grade 3-4 adverse events were decreased white blood cell count (3 [14.3%]), decreased platelet count (2 [9.5%]) and anemia (2 [9.5%]). Immune-related AEs (irAEs) were all G1-2, and occurred in 2 (9.5%) patients. None of the patients discontinued treatment because of intolerable toxicity. Conclusions: In this study, cadonilimab containing therapies showed promising results in responses and survival outcomes among patients with metastatic or recurrent cervical cancer and have a favorable safety profile. [Table: see text]

31P Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study

31P Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study

Cost-effectiveness of tisotumab vedotin as a second- or third-line therapy for cervical cancer.

To evaluate the cost-effectiveness of tisotumab vedotin to treat recurrent or metastatic cervical cancer in second- or third-line from the U.S. payer perspective. A Markov model with three-state was employed to simulate recurrent or metastatic cervical cancer patients who were administered either tisotumab vedotin or investigator's choice of chemotherapy based on the phase III, open-labeled innovaTV 301 randomized clinical trial. The data on cost and health preferences were collected from the literature. Tisotumab vedotin generated an additional 0.25 quality-adjusted life-years (QALYs) compared to chemotherapy, but at an additional cost of $206,779. This results in incremental cost-effectiveness ratios of $839,107.88 per QALY. The results of the univariate sensitivity analysis indicated that cost of tisotumab vedotin, utility of progressive disease and progression-free survival had the greatest impacts on the outcomes. Probability sensitivity analysis showed that tisotumab vedotin had a 0% chance of being considered cost-effective. Tisotumab vedotin was unlikely cost-effective compared to chemotherapy for recurrent or metastatic cervical cancer patients at a willingness-to-pay threshold of $150,000/QALY from the perspective of a U.S. payer. Lowering the prices of tisotumab vedotin could potentially enhance its cost-effectiveness.

The Role of Radiation Therapy for Metastatic Cervical Cancer

Survival rates for women with metastatic cervical cancer (CC) are low, with limited management options. Radiation therapy (RT) for metastatic disease has led to prolonged survival in other malignancies, however, the data are scarce in CC. Herein, we evaluated the effect of RT for metastatic CC. A total of 58 patients with metastatic CC between September 2019 and January 2023 were retrospectively analyzed. All the patients were treated with platinum-based chemotherapy combined with targeted therapy or immunotherapy followed with or without RT (NRT). The recent efficacy, survival status and prognostic factors were analyzed statistically. Objective response rate (ORR) was 63.6% with one complete and twenty partial responses in RT group (n = 33) and 40.0% with two complete and eight partial responses in NRT group (n = 25), respectively (p = 0.074). Disease control rate (DCR) of the RT and NRT groups were 79.4% vs 80.0%, respectively (p = 0.861). Median follow-up time was 17 months (3-39months). In RT group, 11(33.3%) patients experienced local regional or distant failure and 9 (27.3%) patients were dead. In NRT group, 15(60%) patients had progression and 8 (32%) patients dead. There was no significant difference between the two groups in overall survival (OS); however, RT group displayed superior progression-free survival (PFS) (1-year OS: 72.7% vs. 68.0%, p = 0.460; 1-year PFS: 66.7% vs. 40.0%, p = 0.039). The multivariate analysis showed that RT, immunotherapy, lymph node metastasis only relevant predictor of superior PFS but not OS. In subgroup analysis, patients treated with RT appeared to have a better PFS in some specific cohorts, such as age>45 years (72.0% vs 36.4% P = 0.015), squamous carcinoma histology (71.0% vs 40.9% P = 0.017), metastatic at diagnosis (75.0% vs 47.6% P = 0.012), non-targeted therapy (72.4% vs 43.8% P = 0.040). No significant increase in treatment-related toxicity was observed in the RT group compared with the NRT group. RT provided superior PFS in metastatic CC patients compared to NRT, and well tolerated. Moreover, RT, immunotherapy, lymph node metastasis only were independent significant prognostic factors for PFS. Subgroup analysis showed that combination of RT and chemotherapy obtained favorable PFS in metastatic CC patients with age>45 years, squamous carcinoma histology, metastatic at diagnosis, non-targeted therapy. Studies with a larger sample size and longer follow-up are warranted.

Patient profiles, treatment patterns, and outcomes among persistent, recurrent, or metastatic cervical cancer patients under routine care in the United States

ObjectivePatients with persistent, recurrent, or metastatic cervical cancer have poor prognosis. While recent advances have expanded treatment options, real-world data on treatment patterns and outcomes in this population are lacking. MethodsThis retrospective study identified adult females with persistent, recurrent, or metastatic cervical cancer from the ConcertAI Oncology Dataset who received systemic therapy on or after August 15, 2014. Patients were followed from persistent, recurrent, or metastatic diagnosis through third-line (3 L) therapy, death, end of record, or study end (June 2021). Data collection included patient characteristics, treatment patterns, and clinical outcomes. Kaplan-Meier methods were used for the three most common first-line (1 L) regimens to analyze real-world time on treatment (rwToT), real-world progression-free survival (rwPFS), and real-world overall survival (rwOS). Analyses were stratified by bevacizumab receipt by treatment line. Results307 patients were included (mean [standard deviation] age 51.5 [13.2] years, 70.7% White). 91.2% of patients had metastatic disease, 8.5% had persistent disease, and <1% had recurrent disease. The most common 1 L regimen was carboplatin+paclitaxel+bevacizumab (40.7%) with median (95% confidence interval [CI]) rwToT of 3.5 (2.9–4.4) months. 57.0% of patients proceeded to second line (2 L), and 25.7% went to 3 L. Median (95% CI) rwPFS was 7.2 (6.4–8.1) months, and median (95% CI) rwOS was 16.5 (14.2–19.9) months, from initiation of 1 L. Conclusions1 L regimens received in patients with persistent, recurrent, or metastatic cervical cancer generally followed clinical guidelines, and the rwOS agrees with clinical trials. This study highlights the burden of disease and unmet need for specific treatments in these patients.

Prognostic impact of adding bevacizumab to carboplatin and paclitaxel for recurrent, persistent, or metastatic cervical cancer

ObjectiveRecent randomized phase III trial has shown significant benefit in overall survival (OS) for patients with advanced cervical cancer by adding bevacizumab to conventional chemotherapy. The aim of this study was to evaluate the prognostic impact for Japanese recurrent, persistent, or metastatic cervical cancer patients where bevacizumab was added to paclitaxel plus carboplatin. Materials and methodsA retrospective analysis was performed on 90 patients with recurrent, persistent, or metastatic cervical cancer mainly treated by paclitaxel plus carboplatin between 2005 and 2019 at our hospital. Data for the following clinicopathological variables were analyzed: (1) bevacizumab use; (2) histology; (3) disease presentation; (4) performance status; (5) prior chemotherapy containing platinum agent; (6) pelvic disease; (7) prior pelvic radiotherapy; (8) location of target lesions. Survival analysis was performed using Kaplan–Meier curves, log-rank tests, Wilcoxon tests, and Cox proportional hazards models combined with propensity score matching. ResultsAdding bevacizumab to paclitaxel plus carboplatin showed significantly increased complete response to compared with that of non-users. In a Cox regression hazard model, bevacizumab use tended to show better OS though without statistically significance. After propensity score matching, adding bevacizumab to paclitaxel plus carboplatin showed a significant better OS by univariate analysis using Wilcoxon test, not by log-rank test. ConclusionAdding bevacizumab to paclitaxel plus carboplatin showed a limited prognostic impact for recurrent, persistent or advanced cervical cancer patients in the real world. Further effective second-line treatments are needed to prolong OS of patients with recurrent, persistent or advanced cervical cancer.

Real-world treatment pattern and drop-off among recurrent or metastatic cervical cancer patients: A US community oncology-based analysis (304)

Objectives: Recurrent or metastatic cervical cancer (r/mCC) treatment pattern and data on subsequent therapy utilization following first-line (1L) are limited. Additionally, there is no current real-world data on the proportion of eligible second-line (2L) patients who received treatment following progression on chemotherapy doublet +/- bevacizumab. These data are needed to inform clinical trials and treatment algorithms as new therapies become available for the r/mCC patient population, which historically has had poor outcomes characterized by poor overall survival under conventional treatments. Methods: An observational study was conducted among women with r/mCC who initiated 1L systemic therapy within the US Oncology Network (USON) between September 2014 and December 2019, with follow-up through December 2020. USON’s electronic health record was used to identify eligible patients and abstract data. Patient clinical characteristics, treatment pattern, the proportion of patients receiving 2L therapy, and duration of 1L treatment were evaluated. Results: A total of 262 r/mCC patients were identified (mean age: 53 years). Over half of patients (n=143, 55%) had an ECOG performance status score of ≤1, with most patients (72%) having undergone prior radiation or surgery, and histology subgroups generally represented reflective of that reported in the literature for cervical malignancy. Most patients received chemotherapy doublet + bevacizumab (n=174, 66%) or chemotherapy doublet alone (n=62, 24%) as their 1L systemic therapy. The median treatment duration was 4.1 months (0.03-38.4 months). A total of 125 patients (48%) received 2L therapy. In 2L, there was no clear treatment of choice, including cytotoxic monotherapy (n=40), combination therapy (n=39), and pembrolizumab monotherapy (n=35). Of note, a substantial number of patients discontinued 1L for any reason but did not receive 2L treatment, including those progressing on 1L (n=31, 12%), and after discontinuing 1L for other reasons (n=23, 9%). Conclusions: In this real-world retrospective observational study, most patients received the current standard of care systemic therapy in the 1L for treatment of r/mCC. However, less than half of patients received subsequent treatment after completing 1L. Of the patients who received 2L therapy, there was no single clear choice of therapy for patients. As novel and more effective therapies become available, more r/mCC patients needing subsequent treatment may benefit from these emerging options. Objectives: Recurrent or metastatic cervical cancer (r/mCC) treatment pattern and data on subsequent therapy utilization following first-line (1L) are limited. Additionally, there is no current real-world data on the proportion of eligible second-line (2L) patients who received treatment following progression on chemotherapy doublet +/- bevacizumab. These data are needed to inform clinical trials and treatment algorithms as new therapies become available for the r/mCC patient population, which historically has had poor outcomes characterized by poor overall survival under conventional treatments. Methods: An observational study was conducted among women with r/mCC who initiated 1L systemic therapy within the US Oncology Network (USON) between September 2014 and December 2019, with follow-up through December 2020. USON’s electronic health record was used to identify eligible patients and abstract data. Patient clinical characteristics, treatment pattern, the proportion of patients receiving 2L therapy, and duration of 1L treatment were evaluated. Results: A total of 262 r/mCC patients were identified (mean age: 53 years). Over half of patients (n=143, 55%) had an ECOG performance status score of ≤1, with most patients (72%) having undergone prior radiation or surgery, and histology subgroups generally represented reflective of that reported in the literature for cervical malignancy. Most patients received chemotherapy doublet + bevacizumab (n=174, 66%) or chemotherapy doublet alone (n=62, 24%) as their 1L systemic therapy. The median treatment duration was 4.1 months (0.03-38.4 months). A total of 125 patients (48%) received 2L therapy. In 2L, there was no clear treatment of choice, including cytotoxic monotherapy (n=40), combination therapy (n=39), and pembrolizumab monotherapy (n=35). Of note, a substantial number of patients discontinued 1L for any reason but did not receive 2L treatment, including those progressing on 1L (n=31, 12%), and after discontinuing 1L for other reasons (n=23, 9%). Conclusions: In this real-world retrospective observational study, most patients received the current standard of care systemic therapy in the 1L for treatment of r/mCC. However, less than half of patients received subsequent treatment after completing 1L. Of the patients who received 2L therapy, there was no single clear choice of therapy for patients. As novel and more effective therapies become available, more r/mCC patients needing subsequent treatment may benefit from these emerging options.

Real-world treatment drop-off among recurrent or metastatic cervical cancer patients: A US community oncology-based analysis

ObjectiveUnderstanding real-world treatment patterns and proportions of eligible patients in each line of treatment is imperative to inform future clinical trial designs and multi-line treatment algorithm development. MethodsWe conducted a retrospective observational cohort study of adult women who received first-line (1 L) therapy for r/mCC between 01 September 2014 and 31 December 2019, using The US Oncology Network electronic health records and chart review data. Patients were followed to 31 December 2020. Patient demographic and clinical characteristics, treatment patterns, and clinical outcomes were assessed descriptively. ResultsA total of 262 patients with r/mCC met study inclusion criteria (mean age = 53 years). The majority of patients in 1 L received platinum-based chemotherapy doublet plus bevacizumab (66%) or chemotherapy doublet alone (24%). Nearly half the patients (48%) completing 1 L received 2 L therapy. Among these patients, there was no consistent 2 L treatment of choice. Overall median time to treatment discontinuation was 3.5 months from 1 L treatment initiation, and median overall treatment-free interval was 2.1 months from 1 L discontinuation. Besides elevated serum creatinine, abnormal BMI indicated a directional trend for lower likelihood of receiving 2 L. Other predictors may include no prior bevacizumab, worse ECOG, and earlier disease prevention. Conclusions>50% of the patients who initiated 1 L treatment did not receive 2 L therapy, highlighting the need for novel and effective treatment options. As the treatment landscape continues to evolve, we anticipate that more patients will live longer with more treatment options across multiple lines of therapies in the r/mCC setting.

O14-3 Real-world treatment patterns among metastatic cervical cancer patients in Japan

In Japan, there has been an increase in the number of cervical cancer (CC). Patients with recurrent or metastatic CC have limited treatment options. This study described real-world treatment patterns among patients with metastatic CC (mCC) in Japan.

Role of locoregional surgery in treating FIGO 2009 stage IVB cervical cancer patients: a population-based study

ObjectiveWe aimed to analyse the clinical value of primary site surgery in improving the cancer-specific survival (CSS) and overall survival (OS) of initial metastatic cervical cancer patients.DesignA population-based retrospective study.SettingNational...

Immunotherapy and Systemic Therapy in Metastatic/Recurrent Endometrial and Cervical Cancers

Despite advances in the treatment of gynaecological malignancies, both recurrent endometrial and cervical cancers when not amenable to localised therapy (surgery or radiotherapy), remain incurable with limited prognosis and effective treatment options. Chemotherapy remains the standard of care for women with metastatic endometrial or cervical cancers. The addition of bevacizumab to first-line chemotherapy for metastatic cervical cancer patients represents a significant step forward in improving survival. More recently, immunotherapeutic strategies targeting the PD-1/-L1 pathway have shown clinical activity in both endometrial and cervical cancers. The increased understanding of the molecular biology of these cancers is shaping target-specific treatments. Here we summarise current treatment options and results from clinical trials of immunotherapy and other targeted therapies that have already changed, or have the potential to change, clinical practice in metastatic/recurrent endometrial and cervical cancer.

PCN38 A Literature Review Of Recurrent Or Metastatic Cervical Cancer Disease Burden, Treatment Outcomes, And Unmet Needs

We analyzed publicly available data on disease burden, clinical outcomes with novel therapies, and unmet needs for recurrent or metastatic (Rec/Met) cervical cancer (CC) patients. A targeted literature review was conducted in MEDLINE/Embase (January 2010-April 2020) of studies on Rec/Met CC burden and clinical outcomes with therapies including bevacizumab combination therapy (BEVA), pembrolizumab, and topotecan in randomized controlled trials and observational studies. A total of 41 publications, including 32 unique clinical outcomes studies, were descriptively summarized. The global incidence and mortality rates for CC were 13.1/100,000 and 6.9/100,000 women in 2018, respectively. Metastatic CC patients’ mortality was 3 times higher than nonmetastatic CC (58.7% vs 18.5%; years 2005-2010). Sample size was small in most clinical outcomes studies; 63% of the 32 studies had <30 patients. Among all 32 studies, median progression-free survival (mPFS) ranged from 2.0 (pembrolizumab) to 13.1 (BEVA) months and median overall survival (mOS) ranged from 6.4 (topotecan) to 26.0 (BEVA) months. Only 31% (10/32) of the studies reported clinical outcomes by treatment line. In the first-line setting, mPFS ranged from 6.3-12.0 months, mOS ranged from 13.2-21.5 months, and objective response rate (ORR) ranged from 35%-59% with BEVA; mPFS was 7.1 months, mOS was 13.2 months, and ORR was 35% with topotecan. In studies of second or later lines of therapy, mPFS was 4.1 months and mOS was 5.2 months with BEVA; mPFS was 2.0 months, mOS was 11.0 months, and ORR was 11% (17% in PD-L1–positive patients) with pembrolizumab; mPFS was 2.5 months, mOS was 6.4 and 7.3 months, and ORR was 0% with topotecan. Clinical treatment outcomes, including OS, PFS, and ORR, among Rec/Met CC patients are poor and become progressively worse in second and later lines. Innovative treatments are needed to address the unmet needs for Rec/Met CC patients.

PCN292 Economic and Humanistic Outcomes Associated with Treatment of Recurrent or Metastatic Cervical Cancer: A Literature Review

To synthesize the economic and humanistic burden associated with treatment of patients with recurrent or metastatic cervical cancer. A systematic literature review was conducted in Medline and Embase (2010-April 2020) of any published study (real-world studies or clinical trials) of recurrent/metastatic cervical cancer treatments. Articles and abstracts with patient-reported outcome (PRO), cost, or resource utilization were included. Twelve publications were included (11 metastatic/recurrent setting; 1 metastatic setting). Line of therapy was not reported for most publications (not reported, n=10; first-line, n=1; second-line, n=1). Eight publications contained economic outcomes (6 US, 1 UK, 1 South Korea); 4 publications contained humanistic outcomes (4 for chemotherapies, 1 for chemotherapy plus bevacizumab, 1 for chemotherapy plus cediranib). Cisplatin/paclitaxel was cost-effective in a UK Markov model (incremental cost-effectiveness ratio [ICER] £17,974) and 2 US models (ICER $10,928 and $13,654) compared to other chemotherapy regimens. Bevacizumab + chemotherapy was not cost-effective in 4 US models. Adverse event (AE) costs accounted for 55% to 93% of total treatment-related costs depending on the chemotherapy regimen. The Functional Assessment of Cancer Therapy - Cervix (FACT-Cx; n=3), FACT - Neurotoxicity subscale (n=2), Brief Pain Inventory (n=3), and EORTC-QLQ C30 (n=1) were used to measure humanistic outcomes. o difference was found in overall quality of life (QOL) or pain outcomes between bevacizumab/cediranib + chemotherapy versus chemotherapy alone. Physical well-being at baseline was correlated with overall survival outcome. Limited data were found on economic and humanistic outcomes in recurrent or metastatic cervical cancer patients. Data indicate cisplatin/paclitaxel therapy was cost-effective compared to other chemotherapies. Bevacizumab + chemotherapy was not cost-effective despite being recommended as first-line therapy. Overall QOL was not compromised with newer therapies, reflecting benefits from symptom control, although patients experienced more AEs. Novel therapies that can improve economic/humanistic outcomes are needed.

LINC00636 promotes lymph node metastasis and cervical cancer through targeting NM23.

Background: Metastasis is a major obstacle in treatment of cervical cancer, and long non-coding RNA (lncRNA) mediated regulatory effect on associated genes expression is found to be involved in metastasis. However, its mechanisms have not been fully elucidated.Materials and methods: Specimens from patients with cervical cancer metastasis and non-metastasis were used to screen out candidate non-coding RNAs (ncRNAs) and possible downstream targets. And then, effects were determined in vitro and in vivo through knockdown and overexpression techniques.Results: LINC00636 was significantly higher in serum and solid tumor cells of metastatic cervical cancer patients than non-metastatic patients. And knockdown of LINC00636 significantly suppressed invasion, proliferation of cervical cancer cells. NM23 expression was negatively regulated by LINC00636 and it mediated anti-tumor effects was partially blocked by overexpression of LINC00636.Conclusion: LINC00636 might promote metastasis of cervical cancer cells through inhibiting NM23 expression.

A 70-Gene Signature for Predicting Treatment Outcome in Advanced-Stage Cervical Cancer

Cervical cancer is the fourth most common cancer in women worldwide. The current approaches still have limitations in predicting the therapy outcome of each individual because of cancer heterogeneity. The goal of this study was to establish a gene expression signature that could help when choosing the right therapeutic method for the treatment of advanced-stage cervical cancer. The 666 patients were collected from four independent datasets. The 70-gene expression signature was established using univariate Cox proportional hazard regression analysis. The 70-gene signature was significantly different between low- and high-risk groups in the training dataset (p = 4.24e−6) and in the combined three validation datasets (p = 4.37e−3). Treatment of advanced-stage cancer patients in the high-risk group with molecular-targeted therapy combined with chemoradiotherapy yielded a better survival rate than with only chemoradiotherapy (p = 0.0746). However, treatment of the patients in the low-risk group with the combined therapy resulted in significantly lower survival (p = 0.00283). Functional classification of 70 genes revealed involvement of the angiogenesis pathway, specifically phosphatidylinositol 3-kinase signaling (p = 0.040), extracellular matrix organization (p = 0.0452), and cell adhesion (p = 0.011). The 70-gene signature could predict the prognosis and indicate an optimal therapeutic modality in molecular-targeted therapy or chemotherapy for advanced-stage cervical cancer.

Gls-010, a novel anti-PD-1 mAb in Chinese patients with recurrent or metastatic cervical cancer: Results from a multicenter, open-label and single-arm phase II trial.

6032 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Previous Phase I study exhibited favorable result of tolerance, preliminary efficacy and 240mg fixed dose q2w was selected as Recommended Phase II Dose (RP2D). This Phase II clinical trial is aimed to further evaluate the safety and anti-tumor activity of GLS-010 in patients with recurrent or metastatic cervical cancer. Methods: PD-L1 positive (combined positive score (CPS) ≥1) patients with recurrent or metastatic cervical cancer who had received one or more lines of chemotherapy were enrolled and received GLS-010 240mg every 2 weeks. Primary endpoint was the objective response rate (ORR) per RECIST 1.1, secondary endpoints included duration of response (DoR) and safety. Results: From May 16th 2019 to December 24th 2019, 44 pts were enrolled and treated in the study. As of December 24th 2019,the median line of prior systemic chemotherapy was 2(range: 1~4), and 59% (26/44) of pts had received ≥2 previous lines of chemotherapy. The median number of GLS-010 doses was 1.5(range: 1~4). 25 pts received response evaluation per investigator review. With a median follow-up of 2.9 months, 7 of 25 evaluable pts achieved a partial response (PR). The ORR was 28% (95% CI, 12.07-49.39), with 7 pts achieving a PR ( 3 of 7 confirmed), 3 pts achieving stable disease (SD) and 15 pts with progressive disease (PD), 1 of which was assessed as dissociated response with treatment ongoing. Median duration of response had not been reached yet. 33 of 44 patients (75%) experienced one or more treatment-related adverse events (TRAEs) per NCI CTCAE v4.03, most of which were grade 1 or 2. The most common TRAEs were Anaemia (15/44), and 73.3% of them were grade 1 or 2. The most common ≥grade 3 TRAE included Anaemia (4/44). As data cut off, only 1 pt discontinued treatment due to adverse event. Conclusions: GLS-010 showed impressive therapeutic activity and manageable safety profile in Chinese recurrent or metastatic cervical cancer patients. Current evidence support further development of GLS-010 in this and more indications. This trial is still ongoing, and we are looking forward to further results. Clinical trial information: NCT03972722.

Abstract 3330: Circulating HPV DNA as a biomarker for metastatic cervical cancer detection, genotyping and monitoring

Abstract Purpose: Circulating cell-free (cf) human papillomavirus (HPV) DNA is a unique tumor marker for metastatic cervical cancers. We developed a method to genotype and quantify blood circulating HPV DNA in patients with metastatic cervical cancer for patient selection, treatment monitoring, as well as informing data on an experimental T cell therapy. Patients and Methods: we developed a digital droplet (dd) PCR method for HPV genotyping and quantification with cfDNA. In a retrospective study, HPV cfDNA was measured in serum samples from nine metastatic cervical cancer patients received tumor-infiltrating lymphocyte (TIL) immunotherapy. cfDNA data were aligned with the tumor HPV data, drug treatment, and clinical outcome. In a HPV screening, the genotyping and DNA copy number of HPV cfDNA from 47 cervical cancer patients were measured and the allele frequencies were determined in relative to total genomic cfDNA of each patient. Results: The ddPCR assay is highly sensitive, specific, and capable of accurate quantification of both HPV16 and HPV18 cfDNA. In the clinical validation, we detected HPV cfDNA from 19/19 (100%) patients with HPV-positive metastatic and recurrent cervical cancer but not in any of the 45 healthy blood donors. The HPV genotype harbored in the patients’ tumors was correctly identified in 87/87 (100%) sequential patient serum samples. Our data showed the use of HPV cfDNA for pharmacokinetic studies, effectiveness on an investigational therapy, and patient monitoring. In three patients who experienced objective responses, a transient HPV cfDNA peak was detected 2-3 days after TIL immunotherapy and a persistent clearance of HPV cfDNA was observed in only two patients with a complete response (CR). Among the HPV positive cases, the median HPV cfDNA allele frequency is above 30% of genomic single copy genes in these cervical cancer patients. Conclusions: We developed and validated a highly sensitive and specific HPV cfDNA genotyping and quantification method. As a promising non-invasive tumor marker, HPV cfDNA may have value in detecting the efficacy of therapeutic agents and monitoring cervical cancer patients in remission. The cfDNA based HPV genotyping is currently being evaluated for patient selection in an experimental T-cell therapy against a specific HPV antigen. HPV cfDNA may also be a potential biomarker for early diagnosis of cervical cancer. Citation Format: Zhigang Kang, Sanja Stevanović, Christian Hinrichs, Liang Cao. Circulating HPV DNA as a biomarker for metastatic cervical cancer detection, genotyping and monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3330.