Li Wang

Camrelizumab Plus Famitinib versus Camrelizumab Alone and Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Cancer: A Randomized, Phase II Study

PURPOSE To compare camrelizumab (an anti-PD-1 monoclonal antibody) plus famitinib (a multitarget receptor tyrosine kinase inhibitor) versus camrelizumab and chemotherapy in recurrent or metastatic cervical cancer (R/M CC). METHODS Patients with pretreated R/M CC were randomly assigned to receive camrelizumab (200 mg intravenously once every 3 weeks) plus famitinib (20 mg orally once daily), camrelizumab, or investigator's choice of chemotherapy. The primary end point was comparison of objective response rate (ORR) per blinded independent central review (BICR) for camrelizumab-famitinib versus camrelizumab in the intention-to-treat population. RESULTS Overall, 105, 54, and 35 patients received camrelizumab-famitinib, camrelizumab, and chemotherapy, respectively. As of April 21, 2023, ORR per BICR was significantly improved with camrelizumab-famitinib compared with camrelizumab (41.0% [95% CI, 31.5 to 51.0] v 24.1% [95% CI, 13.5 to 37.6]; difference, 16.9% [95% CI, 2.1 to 31.7]; one-sided P = .0181). Per investigator, ORR with camrelizumab-famitinib was 42.9% (95% CI, 33.2 to 52.9), notably higher than 22.2% (95% CI, 12.0 to 35.6) with camrelizumab and 14.3% (95% CI, 4.8 to 30.3) with chemotherapy. Median progression-free survival per investigator was prolonged with camrelizumab-famitinib than camrelizumab and chemotherapy (8.1 months [95% CI, 6.2 to 12.4] vs 4.1 months [95% CI, 2.1 to 5.1] and 2.9 months [95% CI, 2.0 to 6.2]). Median overall survival with camrelizumab-famitinib, camrelizumab, and chemotherapy, as of October 19, 2023, was 20.2 months (95% CI, 15.3 to not reached [NR]), 14.9 months (95% CI, 12.6 to NR), and 13.9 months (95% CI, 7.4 to 20.0), respectively. Eighty-nine (84.8%), eight (15.1%), and 18 (60.0%) patients who received camrelizumab-famitinib, camrelizumab, and chemotherapy, respectively, experienced grade ≥3 treatment-related adverse events. CONCLUSION Camrelizumab plus famitinib improved antitumor activity while exhibiting a manageable safety profile in patients with pretreated R/M CC, potentially offering a novel treatment option.

Clinical response and safety of apatinib monotherapy in recurrent, metastatic cervical cancer after failure of chemotherapy: a retrospective study

To observe the safety and short-term efficacy of apatinib in the treatment of recurrent, metastatic cervical cancer in patients who have already received more than two kinds of comprehensive treatment. Forty-eight patients with recurrent or metastatic cervical cancer after radiotherapy or surgery who received apatinib between June 2016 and June 2017 were involved in this study. These patients experienced progression after first-line or second-line chemotherapy. There were 38 patients with cervical squamous cell carcinoma, 8 with adenocarcinoma, and 2 with adenosquamous carcinoma. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and evaluated. All patients had complete follow-up records, and the median follow-up time was 14.5 months (5.5-20.5 months). Among the 48 patients, 14.58% achieved a partial response and 52.08% achieved stable disease. The overall response rate and disease control rate were 14.58% and 66.67%, respectively. The median time that the 48 patients received oral apatinib was 8.2 months. The median PFS was 4.6 months (95% confidence interval [CI]=3.31-5.26) and OS was 13.9 months (95% CI=8.37-17.96). The main apatinib-related adverse reactions were leukopenia (37.5%), neutropenia (41.67%), hemorrhage (37.5%), hypertension (33.33%), proteinuria (12.5%), fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1-2, and no drug-related death occurred. Apatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients.

Efficacy and Safety of the Anti–PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study

Abstract Purpose: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti–programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer. Patients and Methods: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1–positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%–24.5%]. Median PFS was 4.44 months (95% CI, 2.37–5.75 months), and the median OS was 14.72 months (95% CI, 9.59–NE months). ORR of PD-L1–positive patients was 16.7%, and the ORR of PD-L1–negative patients was 17.9%. No treatment-related deaths occurred. Conclusions: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti–PD-1/PD-L1 mAbs.

HPV‐Induced MiR‐21 Promotes Epithelial Mesenchymal Transformation and Tumor Progression in Cervical Cancer Cells through the TGFβ R2/hTERC Pathway

Cervical cancer (CC) is a common malignant tumor in women. It ranks first among the malignant tumors of woman reproductive organs and is one of the most important cancers in the world. Current studies suggest that human papillomavirus (HPV) infection, especially high‐risk persistent infection, is the basic cause of cervical precancerous lesions and cervical cancer. MicroRNA‐21 (miR‐21) plays a role similar to oncogenes in the occurrence and growth of malignant tumors and can be developed as a potential target for treating malignant tumors. Recently, the study of the mechanism of malignant invasion and metastasis has made great progress. The current consensus is that the invasion and metastasis of malignant tumors is a complicated biological process with multistep and multigene control; the process of epithelial mesenchymal transition (EMT) may be the initial event of invasion and metastasis of epithelial malignant tumors. EMT means that epithelial cells obtain the characteristics of mesenchymal cells, which has main characteristics such as the loss of epithelial cell characteristics and the achievement of mesenchymal cell features, and then induce epithelial cells to acquire the ability of migration and invasion, and participate in many physiological and pathological processes of human body, including embryogenesis, organ differentiation, tissue inflammation, and wound healing. Research has proved that miR‐21 is associated with the invasion and metastasis of cervical cancer, and its specific mechanism has not been completely clear; EMT exerts a significant effect on the invasion and metastasis of epithelial malignant tumors; we speculate whether miR‐21 regulates the EMT process of cervical cancer cells. ELISA and RT‐PCR studied HPV‐induced cervical cancer cells, and it was found that HPV may induce miR‐21 to pass through the TGF β R2/hTERC pathway which promotes epithelial stromal transformation and tumor progression of cervical cancer cells.

Self-Advocacy Among Women With Uterine Malignancies

Background Self-advocacy plays a crucial role in the mental health and treatment outcomes of oncology patients, particularly those with uterine malignancies. Despite its significance, research on the self-advocacy levels and influencing factors among Chinese patients with uterine malignancies remains limited. Objectives To assess the self-advocacy levels among Chinese patients with uterine malignancies and identify the demographic, psychological resilience, and decision self-efficacy factors that influence self-advocacy. Methods This cross-sectional study was conducted from March 1 to September 1, 2023, involving 220 inpatients with uterine malignancies from three tertiary hospitals in Shandong Province, China. Participants were recruited using convenience sampling and completed the General Information Questionnaire, Female Cancer Survivorship Self-advocacy Scale, Connor–Davidson Resilience Scale, and Decision Self-efficacy Scale. Results The average self-advocacy score among participants was 59.44 ± 10.14. Significant positive correlations were found between self-advocacy, psychological resilience, and decision self-efficacy. The random forest algorithm identified decision self-efficacy, psychological resilience, family average income, type of medical insurance, educational level, and residence as the six most important influencing factors, with the optimal model performance observed when lambda (λ) = 1.191. Multiple linear regression analysis further confirmed that decision self-efficacy, psychologic resilience, family average income, educational level, and residence were significant predictors of self-advocacy. Discussion The self-advocacy levels of Chinese patients with uterine malignancies were relatively low, with decision self-efficacy, psychological resilience, and socioeconomic factors significantly influencing their self-advocacy abilities. Future targeted interventions should focus on enhancing patients’ decision self-efficacy and psychological resilience, thereby guiding them to actively respond and participate in decision-making, ultimately improving self-advocacy among patients with uterine malignancies.

First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial

First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer. ClinicalTrials.gov Identifier: NCT03635489.

Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study

Abstract Purpose: Immune checkpoint inhibitors (ICI) have been a potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC (recurrent and/or metastatic cervical cancer). Patients and Methods: Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab 15 mg/kg every 3 weeks (Q3W) plus chemotherapy), cohort A-10 (cadonilimb 10 mg/kg Q3W plus chemotherapy), and cohort B-10 (cadonilimab 10 mg/kg Q3W plus chemotherapy and bevacizumab). They received the corresponding treatments until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. The primary objective was safety; the secondary endpoints included objective overall response (ORR), duration of response, disease control rate, progression-free survival, and overall survival. This study is registered with ClinicalTrials.gov (NCT04868708). Results: As of February 13, 2023, treatment-related adverse events (TRAE) occurred in 45 (100.0%) patients. Grade ≥3 TRAEs were reported in 33 (73.3%) patients. Immune-related adverse events (irAE) occurred in 29 (64.4%) patients and grade ≥3 irAEs were observed in 9 (20.0%) patients. Seven (15.6%) of 45 patients permanently discontinued cadonilimab treatment due to TRAEs. One death due to hemorrhagic shock occurred in cohort B-10. Among 44 patients who underwent at least one post-baseline tumor assessment, the ORR was 66.7% in cohort A-15, 68.8% in cohort A-10, 92.3% in cohort B-10, and 79.3% in cohorts A-10 and B-10 combined. Conclusions: Cadonilimab combined with standard therapy was acceptable, with encouraging antitumor activity in patients with R/M CC.

A Study of SHR-1210± SHR-1020 Versus Chemotherapy in Patients With Recurrent or Metastatic Cervical Cancer

This is a randomized, open-label, 3-arm Phase 2 study to evaluate the efficacy and safety of SHR-1210 alone or with SHR-1020 versus physician's choice chemotherapy in recurrent or metastatic cervical cancer patients. All enrolled patients will be randomly divided into 3 groups and receive treatment until disease progression, intolerable toxicity，any criterion for stopping the study drug or SHR-1210 treatment for up to 2 years.

A Clinical Study of PD-L1 Antibody ZKAB001（Drug Code） in Recurrent or Metastatic Cervical Cancer

This is a Phase 1, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics(PK) of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system) administered every 14 days in subjects with recurrent or metastatic cervical cancer.