bluuebunny/crossref_metadata_2025_split huggingface dataset:
SHR-1701 in combination with platinum-based chemotherapy and BP102 (a bevacizumab biosimilar) for persistent, recurrent, or metastatic cervical cancer: Data from a phase 1b/3 study.
Authors: Liu Jihong , Zhou Yun , Wang Yili , Wang Jing , Wang ShanBing , Li Jin , Wang Xiaohong , Li DaPeng , Wang Li , Liang Fan , Zhou Xianfeng , Wang Linna 
Published: June 2023

5529 Background: Platinum-based chemotherapy (chemo) ± bevacizumab is the standard first-line therapy for cervical cancer, regardless of PD-L1 expression. SHR-1701 is a novel bifunctional fusion protein targeting PD-L1 and TGF-βRII, and shows promising efficacy and controllable safety in pretreated patients (pts) with cervical cancer. This ongoing phase 1b/3 study aims to assess the addition of SHR-1701 to standard first-line therapy. Methods: In the phase 1b part, eligible pts had persistent, recurrent, or metastatic squamous-cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix not previously treated with systemic chemo for recurrence or metastasis and not amenable to curative treatment. Prior chemo-radiotherapy was permitted for recurrence, if mono-chemo was used as sensitizer. Pts were given SHR-1701 (30 mg/kg), paclitaxel (175 mg/m2), cisplatin (50 mg/m2) / carboplatin (AUC 5), and BP102 (15 mg/kg) every 3 weeks. The primary endpoints were safety and ORR. Results: From Feb 26 to Aug 12, 2022, 31 pts were enrolled. Median age was 55 years (range, 27-71). 24 (77.4%) had squamous-cell carcinoma, and 7 (22.6%) had adenocarcinoma. 20 (64.5%) had metastatic disease, 7 (22.6%) had recurrent cervical cancer, and 4 (12.9%) had persistent cervical cancer. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 25 (80.6%) pts, with the most common being decreased neutrophil count (n=16, 51.6%), decreased white blood cell count (n=12, 38.7%), and anemia (n=8, 25.8%). TRAEs led to discontinuation of any study agent in 8 (25.8%) pts; of note, only 2 (6.5%) pts discontinued SHR-1701 due to TRAEs (grade 3 infusion reaction and grade 3 immune-mediated rash). No treatment-related deaths occurred. Efficacy outcomes are summarized in Table. ORR was 77.4%, with 4 CRs and 20 PRs; responses were ongoing in all 24 responders. DCR was 93.5%. Shrinkage in target lesions was observed in 30 (96.8%) pts. PFS rate at 6 months reached 93.5%. Conclusions: SHR-1701 plus platinum-based doublet chemo and BP102 provided a manageable safety profile and potent antitumor activity in pts with persistent, recurrent, or metastatic cervical cancer, supporting the subsequent randomized, double-blind, placebo-controlled phase 3 part. Clinical trial information: NCT05179239 . [Table: see text]
Efficacy and safety of combining PD-1 blockage and human papillomavirus vaccine for patients with relapsed/refractory advanced cervical cancer.
Authors: Wang Buhai , Gu Juan J , Wu Yuechao , Zeng Yichun , Liang Yichen , Liu Liqin , Wu Yinxia , Huang Yuxiang , Li Qiuxian , Chen Caiyue 
Published: June 2023

5530 Background: The prognosis for patients with relapsed/refractory advanced cervical cancer is dismal with a 5-year survival rate of 17%. Limited treatment options were available including platin based therapy, antiangiogenic therapy and immune therapy. Immune checkpoint blockage with anti-programmed cell death 1 (PD-1) antibodies had an overall response rate of 17% among a minority of patients. Recently a phase II study showed human papillomavirus (HPV) 16 vaccination amplified PD-1 antibodies in incurable HPV16 positive cancer with an ORR of 33%. But the study enrolled majority were oropharyngeal cancer patients (92%). Here, we designed and conducted phase II clinical trial to assess the efficacy and safety of combining anti-PD-1 antibody and HPV vaccination for patients with relapsed/refract cervical cancer. Methods: In this single-arm, single-center phase II clinical trial, patients with relapsed/refract cervical cancer were registered (NCT04096911) and enrolled from Dec, 2019 to Dec, 2022 in Department of Oncology, Northern Jiangsu People's Hospital, Yangzhou, China. All patients received prior radiation therapy and had at least one or more lines of therapies. Duration of follow up for censored patients was 36 months. The recombinant human papillomavirus quadrivalent vaccine (0.5ml) was given subcutaneously on day 0, third month, and 6th month. Anti-PD-1 antibody, 200mg was given intravenously every 3 weeks starting on day 1 for up to 2 years. Results: As of Dec 21, 2022, thirteen patients were enrolled in the trial. The median age was 55 years (range, 52 to 83 years). The overall response rate was 69.2%. Disease control rate was 84.9%. Median duration of response was 7.07 months (95%CI, 1.94 to 15.8 month). Six patients achieved complete response. Median overall survival was 13.96 month. No grade 3 and 4 toxicity occurred. Conclusions: Our study was the first clinical trial using HPV vaccine as therapeutic agent in advance cervical cancer treatment. Up to date, immunotherapy along in cervical cancer had limited response rate less than 20% and the combination therapies was less than 40%. In our study, the overall response of 69.2%, disease control rate of 84.9% and median overall survival of 13.96 months were significantly higher compared with anti-PD-1 antibody alone or any current available regiment combinations in relapsed/refract advance cervical cancer patients. We also found synergistic effect of T cell and B cell plays an important role in our study. It appears neoantigen associated with tumor was easier to initiate immune response in cervical cancer patients. This is the first time to show employing combined immune therapeutic agents only is a novel effective clinical strategy in relapsed/refract advance cervical cancer. Clinical trial information: NCT04096911 .
The value of progression-free survival at three years as a primary endpoint for studies on radiotherapy in patients with locally advanced cervical cancer: Individual patient data from Chinese National Cancer Center and validation from 27 global randomized trials.
Authors: Yang Xi , An Jusheng , Zhang Yuanyuan , Yang Yong , Jia Shuangzheng , Li Wei , Huang Manni , Wu Lingying 
Published: June 2023

5534 Background: A traditional endpoint for locally advanced cervical cancer (LACC) clinical trials is overall survival with five years of follow-up (5-year OS). The use of a shorter-term endpoint could significantly speed the translation of research findings into practice. The primary hypothesis was that PFS with three years of follow-up (PFS36) is an appropriate primary endpoint to replace 5-year OS. Methods: The primary hypothesis was developed from our individual data, was further investigated using phase III randomized controlled trials (RCTs), and then externally validated by phase II trials and retrospective studies up to 2022. Correlation analysis at the treatment-arm level was performed between 2-, 3-, 4-, and 5-year PFS rates and 5-year OS. Correlation analysis was performed using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. The MEDLINE, Embase, and PubMed databases, together with the Cochrane Central Register of Controlled Trials, were searched from January 1, 1999, to February 2, 2023. Articles eligible for inclusion contained complete survival data. Results: A total of 613 patients with histologically confirmed, FIGO 2009 stage IB–IVA cervical cancer who underwent radiotherapy at our institute from January 2010 to December 2013 were eligible. Individual patient data were pooled to explore the correlation between PFS and the OS trend. The recurrence rates for years 1 through 5 were 12.9%, 7.3%, 3%, 2.3%, and 1.8%, respectively. The median recurrence time was 13 months and the median time from recurrence to death was 12.2 months. Within all the recurrence, 47.3% of recurrences occurred during the first year, 71.4% in the first two years, and 85% in the first three years. Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%. In contrast, a 5-year OS rate of 98.2% was observed in patients who achieved PFS36. Further data were extracted from 27 randomized phase III trials on LACC. The trials included 57 arms, with a pooled sample size of 7,692 patients. In trial-level surrogacy, PFS36 (r2, 0.778) was associated with 5-year OS. Sensitivity analysis demonstrated reasonable overall consistency. The correlation between PFS36 and OS was externally validated using independent phase II trials and retrospective data. In total, 23 studies representing 5,174 patients were included. PFS (r2, 0.719) was found to be associated with 5-year OS. Conclusions: A significant correlation was found between PFS36 and 5-year OS in clinical trials on patients with locally advanced cervical cancer. This correlation was found both within patients and across trials. These results suggest that PFS36 is an appropriate endpoint for LACC trials of radiotherapy-based regimens.
A peptide-based human papillomavirus therapeutic vaccine, PepCan, or Candida adjuvant alone in treatment of cervical intraepithelial neoplasia 2/3 (CIN2/3).
Authors: Nakagawa Mayumi , Evans Teresa , Coleman Hannah , Crane Jasmine , Darwish Nadia , Faulkner Jennifer L. , Jones Amy , Kelly Haley , Lieblong Benjamin , Lu Yong-Chen , Nookaew Intawat , Ou Yang , Quick Charles Matthew , Ussery David , Robeson Michael Scott , Shah Sumit , Shibata Takeo , Spencer Horace , Williams Heather , Greenfield William 
Published: June 2023

5538 Background: A non-surgical alternative for treating CIN2/3 would be desirable for women of childbearing age due to a risk of cervical incompetency in subsequent pregnancies following surgical treatments. PepCan consists of four current good manufacturing-grade HPV 16 E6 peptides and a Candida skin testing reagent (Candin, Nielsen Biosciences), because of Candida’s ability to regress common warts in humans, and to promote T cell proliferation and interleukin-12 secretion in vitro. Methods: In this single-center, randomized, double-blind Phase II study (NCT02481414), women with biopsy-confirmed CIN2/3 were treated with PepCan or Candida (1:1). Four intradermal injections were given 3 weeks apart which were followed with two visits 6 months apart. Histological responses (primary endpoint) were assessed using quadrant biopsies, and those whose lesions regressed to no CIN were considered to be responders. Regression rate of each treatment group was compared to that of a historical placebo group following the same treatment schedule. A sample size of 35 per arm had 93% power to test the null hypothesis that π = 0.29 (historical control placebo rate) and detect a difference of 0.31 with a two-sided type I error of 5%. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events Version 4. Results: Of 99 subjects screened, 81 (81.8%) qualified for vaccination, and 80 received at least one vaccination. No dose-limiting toxicity was observed. With the intention-to-treat analysis, PepCan showed 30.8% efficacy (12 of 39, p=0.16) while Candida demonstrated 47.6% efficacy (20 of 42, p=0.0004). Likewise, with the per-protocol analysis, PepCan showed 45.8% efficacy (11 of 24, p=0.06) and Candida showed 62.1% efficacy (18 of 29, p=0.0002). There was no difference between efficacy of PepCan and Candida. Conclusions: PepCan and Candida treatments are safe. Only Candida was effective in inducing histological regression in the intention-to-treat and per-protocol analyses. Candida could become a new treatment for CIN2/3 by eliciting general immune stimulation similar to checkpoint inhibitors. Clinical trial information: NCT02481414 . [Table: see text]
Surgical resection based on ontogenetic cancer field theory for cervical cancer: 10-year updated results of the MMR study.
Authors: Weydandt Laura , Wolf Benjamin , Dornhoefer Nadja , Aktas Bahriye 
Published: June 2023

5539 Background: Previously published findings from our center suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. In the MMR study we aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumor control without the need for adjuvant radiotherapy. Methods: The Leipzig School Mesometrial Resection Study (MMR study) is an ongoing, prospective, single-center, observational cohort study including patients with primary cervical cancer. All study participants undergo either total or extended mesometrial resection (TMMR or EMMR) and therapeutic lymph node dissection. Because this treatment strategy enables surgical removal of all locoregional at-risk tissues, no adjuvant radiotherapy is necessary, even in the presence of established risk factors. The trial is registered at the German Clinical Trials Register, number DRKS00015171. For this updated analysis, we identified patients in our institutional study database with primary cervical cancer staged IB1 – IIA2 according to the 2009 International Federation of Gynecology and Obstetrics staging system. Using the Kaplan-Meier estimator, we calculated recurrence free and overall survival. Results: Between October 16, 1999, and December 16, 2020, 420 patients were treated per protocol and followed up for a median of 136 months (IQR 77-190). The median age was 42 years (IQR 36-51). 329 patients (78.3%) had stage IB1, 58 (13.8%) stage IB2, 24 (5.7%) stage IIA1 and 9 (2.1%) stage IIA2 disease. Patients had either squamous cell (n = 297, 70.7%), adenocarcinoma (n = 104, 24.8%), adenosquamous (n = 18, 4.3%) or other (n = 1, 0.24%) histology. The nodal status was pN0 in 349 (83.1%) patients and pN1 in 71 (16.9%) of the cases. Clinically occult parametrial involvement was present in 47 (11.2%) patients. 10-year overall survival was 90.2% (95% confidence interval [CI] 87.1-93.4) and recurrence-free survival was 90.6% (95% CI 87.8-93.6). Stratified for lymph node status 10-year overall survival was 91.7% (95% confidence interval [CI] 88.5-95) for pN0 and 83.2% (95% confidence interval [CI] 74.6-92.9) for pN1. Recurrence-free survival was 93.8% (95% CI 91.2-96.5) for pN0 and 75.4% (95% CI 65.9-86.3) for pN1. Conclusions: Despite dispense of adjuvant radiotherapy, patients treated with total or extended mesometrial resection with therapeutic lymph node dissection have excellent survival outcomes. Additional multicenter studies are needed to further investigate and confirm our results. Clinical trial information: DRKS00015171 .
Efficacy and safety of camrelizumab in combination with radiation and chemotherapy for recurrent or metastatic cervical cancer.
Authors: Chen Zhongjie , Yan Bo , Xu Liming , Huang Xin , Li Meng , Wang Jun , Zhu Li , Yuan Zhiyong , Wang Ping 
Published: June 2023

5542 Background: Cisplatin-based concurrent chemoradiation regimens have been suggested to be beneficial in recurrent or metastatic cervical cancer. Immunotherapy has also shown good therapeutic efficacy in recurrent or metastatic cervical cancer. Among them, Pembrolizumab in combination with chemotherapy has been used for first-line treatment of advanced PD-L1-positive cervical cancer. Meanwhile, Camrelizumab has shown good anti-tumor activity and manageable toxicity in patients with locally advanced cervical cancer. The primary objective of this study is to evaluate the efficacy and safety of Camrelizumab in combination with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer. Methods: Patients diagnosed with recurrent or metastatic cervical cancer received Camrelizumab combined with concurrent chemoradiotherapy, radiotherapy:External beam radiotherapy (EBRT) 1.8-2.15 Gy/f, a total of 28 fractions; Brachytherapy: high-risk CTV using image guidance 28 Gy in 4 fractions (18 Gy in 3 fractions for posthysterectomy recurrent patients); chemotherapy regimen used TP regimen (paclitaxel: 175 mg/m2, cisplatin: 75 mg/m2, Q3W 6 cycles); Camrelizumab 200 mg Q3W 6 cycles. The primary endpoint of this trial was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and incidence of adverse reactions. Results: From September 16, 2020 to September 30, 2022, a total of 29 patients were recruited. 27 of these patients completed 6 cycles of planned treatment. 27 patients had a median age of 53 years (33-73 years), ECOG PS 0 (n = 8), ECOG PS 1 (n = 14), ECOG PS 2 (n = 1). The ORR rate was 96.30% (26/27), including 17 patients with CR, 9 patients with PR, and 1 patient with SD Treatment-related AEs were mainly lymphocyte count decreased, anemia, and white blood cell count decreased, with overall safety manageable and no treatment-related deaths. Conclusions: Camrelizumab combined with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer has good efficacy, low side effects and acceptable toxicity. Clinical trial information: NCT04884906 .
Impact of neoadjuvant chemo-immunotherapy on surgical outcomes and time to radiation in triple negative breast cancer.
Authors: Myers Sara P. , Veeravalli Srinivasa Sevilimedu , Jones V. Morgan , Abuhadra Nour , Montagna Giacomo , Plitas George , Morrow Monica , Downs-Canner Stephanie 
Published: June 2023

555 Background: The impact of preoperative chemo-immunotherapy on surgical complications and timing of adjuvant therapy is not well understood. We examined the association between neoadjuvant pembrolizumab plus chemotherapy (NAC+P) compared to neoadjuvant chemotherapy alone (NAC) and treatment delays and postoperative complications in triple negative breast cancer (TNBC). The effect of immune-related adverse events (irAEs) on these outcomes was also compared. Methods: 143 women with stage II-III TNBC treated with NAC+P based on the KEYNOTE 522 (KN522) regimen from 8/2021-9/2022 were compared to 287 consecutive patients who received NAC prior to 7/2021. Baseline characteristics, time to treatments, and surgical complications were compared between KN522 and non-KN522, and among KN522 with/without irAEs using two-sample non-parametric tests. Linear regression evaluated association of irAEs with time to surgery and radiation. Conditional logistic regression identified factors associated with surgical complications among KN522 patients. Results: Age, BMI, race, ASA class, and mastectomy rates were similar among KN522 and non-KN522 patients. Interval from end of neoadjuvant treatment until surgery was one day longer for patients receiving NAC+P (median 32 days (IQR 27, 43) vs. 31 days (26, 37) non-KN522, p = 0.035). Time to radiation did not differ (p = 0.2). Postoperative complications occurred in 26 (9%) non-KN522 vs 12 (8.4%) of KN522 patients (p = 0.7) (Table). 55/144 (38%) of KN522 patients experienced 74 irAE; 42 (76%) required treatment. Pembrolizumab was held in 21 (38%) and discontinued permanently in 17 (31%). One KN522 patient experienced a fatal irAE (pneumonitis). Older age (coeff. 0.38, 95% CI 0.06-0.70, p = 0.02) and ASA class 4 (coeff. 53, 95% CI 14-92, p = 0.009) were associated with delays to surgery but irAE was not (p = 0.070). Neither presence of irAE (coeff. 6.8, 95% CI -0.74-14, p = 0.081) or number of irAEs (coeff. 4.1, 95% CI -1.2-9.3, p = 0.13) were associated with time to radiation. IrAEs were not associated with surgical complications (p = 0.5). Conclusions: Postoperative complications or delays to surgery or adjuvant radiation were similar in patients treated with NAC+P compared to NAC. IrAEs were not associated with delays to surgery or adjuvant radiation or postoperative complications. [Table: see text]
Real-world data from a multi-center study: Insights to the efficacy and safety in patients with ovarian cancer (OC) received niraparib as first-line (1st-L) maintenance therapy (MT).
Authors: Zhao Minmin , Shen Yang , Zhou Ying , Chen Bingwei , Wu Xin , Miao Pengcheng , Jiang Zhi , Zhu Tao , Xu Xizhong , Zhang Bei , Yuan Donglan , Zhang Yang , Sun Wei , He Aiqin , Zhao Min , Hou Wenjie , Shao Zhuyan , Jia Meiqun , Zhu Yanling , Chen Jun 
Published: June 2023

5551 Background: Niraparib has significantly extended PFS as 1st-L MT OC in PRIMA/PRIME. Due to the more complex in treatment and status of the patients (pts) in clinal practice, more real-world data is needed to verify the efficacy and safety of Niraparib. Meanwhile, exploring the link between clinical characters and PFS, may to establish a clinical model to predict Niraparib benefits. Methods: This is a retrospective multicentric study recruiting OC pts received Niraparib as 1st-L MT from fourteen hospitals throughout China from Jan. 2019 to Dec. 2021. The database lock-time was on Dec. 31st, 2022. The pts’ basic characters, especially biomarkers, KELIM scores, etc. were recorded. Survival analyses were conducted using the Kaplan-Meier method and log-rank test, and 95% CI were calculated. The primary endpoint was PFS, and secondary endpoints included time to treatment discontinuation (TTD), time to first subsequent therapy (TFST) and safety. The exploratory endpoint was to establish a clinical prediction model of Niraparib benefits. Results: 199 pts’ data were analyzed. The median(m) follow-up at the time of the data cutoff was 14.93 months (mos) (12.17, 39.47). Baseline characteristics were shown in Table. MPFS was not reached (NR) (29.80 to not be estimated, NE), with maturity 29.64%, and PFS rate at 6, 12, 18, 24mos was 89.4%, 79.5%, 68.3%, 64.5% respectively, showing the efficacy of Niraparib. MPFS (95% CI) in subgroups were as follows: BRCAwt 23.83mos (23.83 to NE); HRD negative 15.63mos (12.6 to NE); KELIM＜1 NR (15.33 to NE); BRCA1/2m, HRD positive and KEILM≥1 subgroups were all NR yet, due to the no longer enough follow-up time and low data maturity. Multivariate analysis found that pts with <65 years, BRCA1/2m, HRD positive, KELIM＞1, and R0 after primary cytoreductive surgery were likely to have longer PFS. The rate of grade ≥3 thrombocytopenia was 19.1%. Treatment discontinuation occurred in 11 (5.5%) pts due to TEAEs. The clinical prediction model for probability of progression was established from 149 pts (training dataset): Score = 0.612 Age ＞65 + 0.3889 BMI≤23.90 + 0.097 FIGOIV + 0.191ChronicN +1.398 Surgery resultR1/R2 +2.552 BRCAwt . The probability of disease progression received Niraparib in 6, 12 and 18m can be obtained by mapping the score to the nomogram. Conclusions: The efficacy and safety of Niraparib in this study are consistent with the results in PRIME. The clinical predictive model established in this database needs more data to be matured and verified. [Table: see text]