Abstract:
OBJECTIVES:To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression. METHODS:In non-randomized phase I expansion cohorts, patients (squamous or non-squamous histology) received cemiplimab 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) or with hfRT during week 2 (combination cohort). Due to insufficient tissue material, PD-L1 protein expression was evaluated in commercially purchased samples and mRNA expression levels were analyzed from The Cancer Genome Atlas (TCGA). RESULTS:Twenty patients enrolled in both cohorts in total; 10 had squamous histology. The most common adverse events of any grade were diarrhea, fatigue, and hypokalemia, occurring in 35%, 25%, and 25%, respectively. Objective response rate was 10% in each cohort; responders had squamous histology. Duration of response was 11.2 months and 6.4 months for the responder in the monotherapy and combination cohort, respectively. Irradiated lesions were not included in the response assessments. In separate archived specimens (N = 155), PD-L1 protein expression in tumor and immune cells was negative (<1%) more commonly in adenocarcinoma than in squamous tumors. PD-L1 mRNA levels were lower in adenocarcinoma than squamous cell tumors (1.2 vs 5.0 mean transcripts per million, respectively) in TCGA. CONCLUSIONS:Cemiplimab has activity in cervical squamous cell carcinoma. The phase I results, combined with results from other anti-PD-1 trials in cervical cancer and our biomarker analyses have informed the design of the ongoing phase III trial, with the primary overall survival hierarchical analyses being done first in patients with squamous histology.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Rischin D,Gil-Martin M,González-Martin A,Braña I,Hou JY,Cho D,Falchook GS,Formenti S,Jabbour S,Moore K,Naing A,Papadopoulos KP,Baranda J,Fury W,Feng M,Stankevich E,Li J,Yama-Dang NA,Yoo SY,Lowy I,Mathias M,Furydoi
10.1016/j.ygyno.2020.08.026subject
Has Abstractpub_date
2020-11-01 00:00:00pages
322-328issue
2eissn
0090-8258issn
1095-6859pii
S0090-8258(20)33827-0journal_volume
159pub_type
杂志文章abstract:OBJECTIVE:Difficulties in detecting cervical adenocarcinoma early are well known. We report a detailed pathology review of cervical adenocarcinoma subtypes, comparing growth patterns and appearance of non-neoplastic epithelium to inform possible clues for disease progression and early detection. METHODS:This analysis ...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2006.03.049
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVES:High grade undifferentiated uterine sarcomas (HGUS) are rare, aggressive malignancies. Data regarding management are limited. We aimed to describe disease stage, response to treatment, and survival outcomes among patients with HGUS at our institution. METHODS:We identified all patients with HGUS who receive...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.06.030
更新日期:2012-10-01 00:00:00
abstract:BACKGROUND:Cervical cancer on the mucosal surface of a pedunculated cervical leiomyoma has not been reported. CASE:A 54-year-old woman who had a bulky protruding cervical tumor with a history of a vaginal bleeding was diagnosed as having squamous cell cancer of the cervix. She received a total of 45 Gy (1.8 Gy daily u...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.12.021
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVE:A prospective psychological evaluation study of familial ovarian cancer screening (PsyFOCS) is underway in partnership with the UK Familial Ovarian Cancer Screening Study (UK FOCSS Phase 2). One of the aims of PsyFOCS is to examine factors associated with withdrawal from the UK FOCSS prior to the onset of 4-m...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2011.09.015
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to profile cervical squamous cell carcinoma in elderly patients undergoing radiation therapy and to study the treatment outcome and side effects of therapy. MATERIALS AND METHODS:A retrospective analysis was carried out from the records of 380 patients with squamous cell carcino...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1999.5722
更新日期:2000-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the long-term outcomes of young early stage cervical cancer patients wishing to preserve their childbearing potential. METHODS:Data of young (aged <40 years) patients with early stage cervical cancer were prospectively collected. All patients with stage IA2, IB1 and IB2 cervical cancer were inclu...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2019.04.007
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Patients who undergo pelvic floor resection as treatment for recurrent cancer following radiation therapy have increased rates of complications, particularly if permanent prosthetic mesh is used for reconstruction. Human acellular dermal matrix (HADM), commonly used for reconstruction in other torso location...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2007.08.063
更新日期:2007-12-01 00:00:00
abstract:OBJECTIVE:Based on previous studies, standard gynecological screening consisting of annual transvaginal ultrasonography (TVU) was added with endometrial sampling in women with Lynch syndrome (LS). The aim of this study was to evaluate the additional value of endometrial sampling in detecting (pre)malignancies of the en...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2013.05.032
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:Previous studies by the Gynecologic Oncology Group have demonstrated a 7% response rate with bolus etoposide as second-line therapy in nonsquamous cell carcinoma of the cervix. Prolonged oral etoposide, which exploits the schedule dependency of this agent, has demonstrated increased activity in squamous carci...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/s0090-8258(03)00079-9
更新日期:2003-05-01 00:00:00
abstract::To determine the effects of neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma Stage IB2 (tumor diameter > 4 cm), we reviewed 52 surgically treated patients diagnosed between January 1987 and December 1993. There were 20 patients treated with preoperative neoadjuvant chemotherapy and 32 treated by ...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1006/gyno.1997.4645
更新日期:1997-05-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to determine the prevalence and types of complementary and alternative medicine (CAM) usage by women with gynecologic cancer in an outpatient midwestern university practice. METHODS:Any patient with a gynecologic cancer seen in the outpatient clinic of the gynecologic oncology divis...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6515
更新日期:2002-03-01 00:00:00
abstract:OBJECTIVE:The purpose of this study is to evaluate the significance of the c-Met/hepatocyte growth factor receptor expression in invasive cervical carcinoma. METHODS:Ninety-Four patients with FIGO stage 1B disease, treated primarily with surgery, were studied immunohistochemically. Of the cases, 67 were squamous carci...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/s0090-8258(02)00073-2
更新日期:2003-02-01 00:00:00
abstract:PURPOSE:Racial genetic admixture (RGA), a measure to account for ancestral genetic background that correlates with individual's racial classification, could provide insights on causation of racial disparity in endometrial cancer (EC). Our objective is to evaluate the association of RGA with EC outcomes. METHODS:EC pat...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2015.11.018
更新日期:2016-02-01 00:00:00
abstract::The altered expression of histocompatibility leukocyte antigens (HLA) in the development to cervical carcinoma suggests that tumor progression may be related to impaired recognition by host immune defense mechanisms. To investigate whether this phenomenon plays a role in the process of metastasis of cervical cancer, w...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1995.1156
更新日期:1995-06-01 00:00:00
abstract:OBJECTIVE:Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular protein that modulates cell adhesion and growth. It is thought to play a decisive role in tissue remodeling and angiogenesis. Alterations in SPARC expression have been observed in a variety of solid tumors; however, no consistent patter...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2000.5894
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVE:This study analyzed a model for the identification of specific epitopes recognized by autologous tumor-reactive humoral responses of endometrial cancer patients as potential markers for the monitoring of cancer. METHODS:The presence of circulating pro- and mature forms of cathepsin D and antibodies reactive ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6120
更新日期:2001-05-01 00:00:00
abstract::Survival rates were computed for 376 women diagnosed with carcinoma of the uterine cervix between 1964 and 1988. The 5-year survival rate for the entire group was 63%. The effect of age at diagnosis, clinical stage, histopathology, year of diagnosis, and screening program attendance was studied by univariate analysis ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(91)90011-s
更新日期:1991-10-01 00:00:00
abstract:BACKGROUND:Traditionally, hysterectomy is considered definitive therapy for cervical adenocarcinoma in situ (AIS) in women beyond childbearing. CASE:A 45-year-old gravida 2, para 2 patient presented with cervical dysplasia and on pathology review of the large loop excision procedure cervical adenocarcinoma in situ was...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.06.044
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVE:There is a need to find agents with activity in platinum and taxane refractory ovarian cancer to be employed as second-line therapy in the malignancy. Limited clinical trial experience has suggested that gemcitabine possesses activity in this clinical setting. We wished to further define the level of activity...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1016/s0090-8258(03)00399-8
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Malignant struma ovarii is a rare tumor, consisting of a struma ovarii with malignant change. Because of the rarity of the tumor, only a few reports with detailed data of thyroid function of the patient have been published. CASE:Medical and surgical treatments were performed in a case of malignant struma ov...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2000.5966
更新日期:2000-12-01 00:00:00
abstract::Forty-two of sixty-seven patients (62.7%) treated for high-risk metastatic trophoblastic disease achieved and maintained complete remissions. The survival rate was significantly improved in those patients with scores lower than 8 according to a modification of the World Health Organization (WHO) prognostic scoring sys...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(89)90106-6
更新日期:1989-07-01 00:00:00
abstract:OBJECTIVE:Patients with recurrent ovarian cancer were treated intraperitoneally (ip) with a replication-deficient recombinant adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene. Vector delivery was followed by intravenous administration of an antiherpetic prodrug and a topoisomerase I inhibitor....
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1006/gyno.2001.6442
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVE:Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix. As shown in the original Japanese group description, in recent studies, GAS represents a more aggressive disease than the usual-type endocervical adenocarcinoma (UEA). Detailed clinicopathological features of...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2019.01.022
更新日期:2019-04-01 00:00:00
abstract::Tumor specimens from 92 patients with ovarian carcinoma were analyzed for estrogen receptor (ER), progesterone receptor (PR), proliferative fraction, and ploidy. Seventy-one percent of tumors were either ER+ (greater than 5 fmole/mg protein) or PR+ (greater than 10 fmole/mg protein) with 27% of tumors overall being bo...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/s0090-8258(89)80031-9
更新日期:1989-02-01 00:00:00
abstract:OBJECTIVE:Primary objective of this study was to determine prognostic significance of Bohm's histopathological regression score in patients who received neoadjuvant chemotherapy (NACT) for treatment of high grade serous (HGS) tubal & ovarian carcinoma. METHODS:This was a retrospective cohort study of patients who rece...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2018.08.042
更新日期:2018-11-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1997.4877
更新日期:1997-12-01 00:00:00
abstract:OBJECTIVE:In the US, second non-ocular malignancies are the primary cause of death in retinoblastoma survivors with the germline RB1 mutation. Soft tissue sarcomas are one of the most likely malignancies to pose a risk to these patients, with leiomyosarcoma (LMS) being the most common subtype. As our cohort is followed...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2011.10.019
更新日期:2012-02-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1016/j.ygyno.2004.09.038
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to determine the incidence of thrombocytosis in epithelial ovarian carcinoma and examine associations with clinico-pathologic features. Thrombocytosis (platelet counts >400 x 10(9)/l) has been identified as a poor prognostic factor in many cancers. Platelet-secreted factors may...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2003.09.002
更新日期:2004-01-01 00:00:00
abstract::Melanoma represents the second most frequent vulvar malignancy, and yet is still considered to be an uncommon neoplasm. Several varieties of melanoma exist. A patient who was diagnosed with a rare subtype of melanoma as a primary vulvar process is presented here. To date, there is only one other reported case of neuro...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1995.1048
更新日期:1995-02-01 00:00:00