Browsing Over 107 Presentations
35P - Racial Disparities in Diagnosis, Histological Type,Treatment and Survival in Ovarian Cancer Patients in the US from 1992 to 2018: SEER-based Analysis.
- Eman I. Zin Eldin (Menoufia, Egypt)
Abstract
Background
Ovarian malignancies are the 7th diagnosed malignancy and the 8th cause of death in females worldwide. Ovarian cancer includes a great heterogeneous group of neoplasms that differs in histological type, pathological stage, risk factors, prognosis, and treatment. Racial disparities in incidence, treatment, and mortality in cancers exist globally. With Surveillance, Epidemiology, and End Results (SEER) program in place, detection of these disparities would be feasible. herein racial disparities in ovarian cancer are analyzed.
Methods
Using SEER*Stat 8.3.9 program and then Case listing session and extracting data from Incidence - SEER Research Data, 13 Registries, Nov 2020 Sub (1992-2018). Patients with malignant behavior and known age diagnosed between 1992 to 2018 and site recode ICD-O-3 WHO 2008(ovary) were included; patients with incomplete data were excluded. Descriptive analysis and Kaplan Miere survival are done using IBM SPSS Statistics 25.
Results
46854 patients were included in the analysis, Non-Hispanic (NH) white race was 69.9% of them followed by the Hispanic group represents 11.8%. There was a great association between races and histology; eta was 0.06, Most predominant histological type was non-invasive low-grade serous carcinoma by 22.9%,20.7%,18.9% in NH white, Hispanic, NH black respectively. 2nd most predominant was Serous tubal intraepithelial carcinoma in NH American Indian/Alaska Native and NH Asian or Pacific Islander by 24.0% and 18.8% respectively. Kaplan Meier analysis revealed the best median survival time of 78 months (95%CI 70.89:85.12, SE 3.63) in NH Asian or Pacific Islander group, followed by Hispanic (All Races) with 56 months (95%CI 52.09:59.91, SE 1.99). The worst survival time was noticed in Non-Hispanic Black with a median survival time of 27 months (95%CI 24.95:29.05 SE 1.04). Log Rank p-value =0.001. Regarding Racial association with staging; eta was 0.04 and distant stage was predominant in all races 68.0%,68.7%,57.7%,67.1%,62.6% for NH White, NH Black, NH Asian or Pacific Islander, NH American Indian/Alaska Native, Hispanic (All Races) respectively.
Conclusions
Our analysis goes along with present literature regarding racial disparities.
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
16P - The role of IL-8 gene polymorphism (845 T/C) in the development of cervical intraepithelial neoplasia
- Tatyana Abakumova (Ulyanovsk, Russian Federation)
Abstract
Background
IL-8 gene polymorphisms are involved in the carcinogenesis of many malignant neoplasms, but their role in the development of cervical cancer (CC) has not been fully elucidated. The aim of the study was to evaluate the relationship between the presence of IL-8 gene polymorphism (845 T/C) and the development of severe cervical intraepithelial neoplasia (CIN) and cervical cancer.
Methods
The study included 21 patients with CIN III and stage Ia FIGO cervical cancer and 20 healthy women (control). The study was conducted in accordance with the requirements of the USU Ethics Commission (No. 9 dated September 15, 2016). We determined the level of IL-8 (CJSC Vector-Best-Volga, Russia) using ELISA in neutrophil lysate and serum. For the analysis of SNP IL-8 845 T/C (rs2227532), the samples were genotyped by PCR with restriction enzyme analysis using Vsp I endonuclease (SibEnzyme, Russia). The digested PCR products were separated by electrophoresis in 1.5% agarose gel. Statistical processing was carried out using Statistica 13 (StatSoft).
Results
We found that the -845C* allele was more common in the group with cervical lesions (76.2%) than in the control group (10%) (chi-square=18.223, p=0.001). The risk of developing CIN increased in the presence of the -845C* allele (OR=28.8, 95% CI 4.892-169.546, p=0.038). The level of IL-8 in neutrophils in CIN (p=0.015) was lower than that in the control. At the same time, the level of IL-8 in neutrophils and serum in CIN is not associated with the frequency of occurrence of the -845T* and -845C alleles.
Conclusions
The presence of IL-8 gene polymorphism (845 T/C) is associated with CIN.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
36P - Factors associated with platinum resistance in ovarian cancer patients receiving neoadjuvant chemotherapy
- Qinglei Gao (Wuhan, China)
Abstract
Background
Currently, researchers have found that neoadjuvant chemotherapy (NACT) which could enhance the stemness of ovarian cancer cells and induce platinum resistance gene mutations is an independent risk factor for platinum resistance. However, there is little data concerning the potential factors contributing to platinum resistance in patients receiving NACT. Herein, we conducted this real-world retrospective study to explore the factors associated with platinum resistance in NACT population.
Methods
Patients with histologically confirmed advanced ovarian cancer (IIIC-IV) who had received NACT at seven hospitals in China were enrolled from May 2004 to June 2020. Univariate and multivariate logistic regressions were performed with odds ratios (ORs) and 2-tailed 95% confidence intervals (CIs) to analyze the impacts of age, type, grade, stage, CA125 level, number of NACT cycles, and postoperative residual disease (R0, no macroscopic residual disease; R1, the maximum diameter of postoperative residual disease ≤ 1cm; R2, the maximum diameter of postoperative residual disease > 1cm) on platinum resistance. Statistical significance was considered at P < 0.05.
Results
A total of 630 patients with stage IIIC-IV ovarian cancer who received NACT were included in the analysis. 316 (50.2%) patients received no more than two cycles of neoadjuvant chemotherapy. Patients with 1 or 2 NACT cycles had a lower rate of platinum resistance recurrence than patients with more than 2 NACT cycles (26.3% vs 35.4%, P = 0.017). In the univariate analyses, Stage IV and more than 2 NACT cycles were risk factors for platinum resistance (OR = 1.44, P = 0.039; OR = 1.54, P = 0.014). Besides, R1 and R2 were also risk factors for platinum resistance (OR = 1.61, P = 0.017; OR = 2.19, P = 0.001). In the multivariate logistic regression analyses, more than 2 NACT cycles was an independent risk factor for platinum resistance (OR = 1.79, P = 0.005). R1 and R2 were also independent risk factors for platinum resistance (OR = 2.00, P = 0.004; OR = 3.17, P < 0.001).
Conclusions
More than 2 cycles of NACT and residual disease were independent risk factors for platinum resistance in advanced ovarian cancer patients receiving neoadjuvant chemotherapy.
Legal entity responsible for the study
Tongji Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
1P - Comprehensive assessment of gene mutations revealed overlapping responses for PARPi and chemotherapy in ovarian cancer cells
- Alessandra Tozzi (Basel, Switzerland)
Abstract
Background
PARP inhibitors (PARPi) have revolutionized the therapeutic landscape of epithelial ovarian cancer (EOC) treatment, showing outstanding benefits in regards to progression-free survival, especially in patients carrying BRCA1/2 mutations or harboring defects in homologous recombination repair. Yet, it remains uncertain which PARPi to choose and how to select responders by using clinical and molecular characteristics, especially in forefront therapy when platinum sensitivity is unknown.
Methods
Through a systematic literature review and the exploration of publicly available CRISPR-Cas9 library screens and Genomics of Drug Sensitivity in Cancer data, we identified potential genes linked with PARPi response. Using a CRISPR-Cas9 mutagenesis assay, we functionally tested 33 genes for PARPi and carboplatin response in six ovarian cancer (OC) cells lines.
Results
ATM was the only tested gene which induced olaparib sensitivity in a cell line-independent manner. Acquired olaparib sensitivity was also observed upon Cas9-mediated loss of MUS81, NBN, RAD51/B/C, RNASEH2A, PALB2, XRCC1, and XRCC3 in at least 3 out of 6 cell lines. As the major survival benefit of PARPi treatment was reported in chemo-sensitive tumors, we next assessed the effect of top candidate genes on olaparib, niraparib, talazoparib, and carboplatin response. Interestingly, we observed identical effects in a gene- and drug compound-independent manner on acquired drug sensitivity, supporting the strong correlation of cancer cell response to PARPi and chemotherapy. In contrast, we identified CDK12 as an essential gene for cell proliferation/survival in ovarian cancer cells, independent of PARPi and chemotherapy treatment.
Conclusions
Our data suggest a general mechanism of response to PARPi and chemotherapy as demonstrated by various overlapping gene dependencies. The screen of the genetic status of the genes identified correlated with PARPi sensitivity may allow better stratification of patients with increased benefit to this treatment.
Legal entity responsible for the study
The authors.
Funding
Swiss National Science Foundation (CRSII5_171037), Griesbach-Hallenstein Foundation (Walter Edwin Griesbach Award and Olga Hallenstein Award), Department of Biomedicine, University Hospital Basel and University of Basel.
Disclosure
All authors have declared no conflicts of interest.
17P - Correlation between human papillomavirus clearance and complete response among Mexican patients with locally advanced cervical cancer treated with chemoradiotherapy
- MARIA F. NORIEGA IRIONDO (Monterrey, Mexico)
Abstract
Background
Currently, there is a paucity of data evaluating post-treatment human papillomavirus (HPV) clearance in patients who receive definitive chemoradiotherapy (CRT) for the treatment of locally advanced cervical cancer and its correlation with oncological outcomes.
Methods
We included patients with histopathologically-confirmed locally advanced cervical cancer who were amenable to definitive CRT and brachytherapy. The subjects underwent a pretreatment liquid-based cytology to perform mRNA-based testing for HPV infection. We repeated the HPV testing 6 weeks after the patients completed their treatment. Response to treatment was evaluated with clinical examination, cervical cytology, and a contrasted pelvic MRI.
Results
Over a 6-month period, 23 patients were included in our study. The mean age at diagnosis was 65 years. Regarding clinical stage (CS), 13% of cases were classified as CS IIA1 non-bulky disease, whereas 87% were classified as CS IB2 to IVB disease. HPV infection was reported in 87% of cases, from which 34% presented more than one HPV genotype. The most prevalent HPV genotype was 16 (48%), followed by 72 (13%) and 18 (9%). Sixteen patients completed the treatment protocol and underwent evaluation for clinical response and post-treatment HPV testing. A complete response (CR) was documented in 81% of cases. Of the sixteen evaluable patients, 13 were initially positive for HPV infection; viral clearance was documented in 8 cases (62%). From all patients who achieved HPV clearance, we documented CR in 54% of cases, whereas only 31% of patients who did not achieve HPV clearance presented a CR. After analysis, we did not find a statistically significant correlation between HPV clearance and CR. HPV clearance was neither correlated with the CS at diagnosis.
Conclusions
Despite the high rate of post-treatment HPV clearance reported among our patients with locally advanced cervical cancer, we found no correlation with achieving a CR. The role of HPV clearance in this setting needs to be further evaluated to determine its value in clinical response and other oncological outcomes like disease-free interval or overall survival.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
37P - Obesity and ovarian cancer, a controversial risk factor
- Firas Baidoun (Cleveland, OH, United States of America)
Abstract
Background
Ovarian cancer is the eighth most common malignancy in females and the third most common gynaecological malignancy in the world. It is the leading cause of gynaecological cancer death in the world. Obesity, which is increasing worldwide, is still a controversial risk factor for ovarian cancer and till now there is no consensus on the obesity role on ovarian cancer. Therefore, we investigated the association between obesity and ovarian cancer using a large inpatient database.
Methods
We used the National Inpatient Sample (NIS) database to review female admissions between 2002 and 2015. Patients were grouped based on the presence or absence of obesity using the appropriate ICD-9 codes. We used a multivariate logistic regression to assess the association between obesity and ovarian cancer.
Results
We reviewed 50,469,770 admissions of which 4,365,971 (8.7%) were obese. Both groups had a similar median age (54 years) but obese patients were more likely to be black (20% vs. 14%, P<.001), have polycystic ovarian syndrome (PCOS) (0.5% vs 0.1%, P<.001), endometriosis (0.9% vs. 0.7%, P<.001) and be smokers (12% vs 9%, P<.001). Family history of ovarian cancer was similar in both groups. After adjusting for age, BRCA1/BRCA2 mutations, family history, lynch syndrome, smoking, IUD, endometriosis, PCOS, infertility, oral contraceptive pills, and hormone replacement therapy, obese patients were significantly less likely to have ovarian cancer (OR=0.821, 95%CI[0.808-0.835], P< .001) compared with patients without obesity. To further assess the association between obesity and ovarian cancer in pre-menopause vs post-menopause, we did a subgroup analysis based on age, the same trend was observed in both patients younger and older than 50 years.
Conclusions
In our large database study, we found that obesity was associated with lower rate of ovarian cancer and that association was seen in both young and older patients. However, the timeliness of obesity in relation to ovarian cancer cannot be determined through the NIS database and thus further prospective epidemiological studies are warranted.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
2P - Spectrum of BRCA1, BRCA1, ATM and PALB2 alleles in ovarian cancer patients from North Caucasus
- Evgeny Imyanitov (Saint-Petersburg, Russian Federation)
Abstract
Background
North Caucasus hosts several large ethnic groups, which preserved their national identity through the course of history. These populations are likely to have a unique pattern of disease-predisposing alleles reflecting the genetic background of their ancestors.
Methods
This study involved 180 ovarian cancer (OC) patients from Chechnya (n = 68), Kabardino-Balkaria (n = 49), North Ossetia (n = 32), Ingushetia (n = 16) and Dagestan (n = 15). The entire coding sequences of BRCA1, BRCA2, ATM and PALB2 genes were analyzed by next-generation sequencing.
Results
OC patients belonging to various ethnic groups had high frequency of BRCA1/2 mutations ranging from 18% to 33%. There were founder pathogenic alleles detected in Chechens (BRCA1 c.3629_3630delAG; 9 out of 15 BRCA1/2 mutations) and North Ossetians (BRCA2 c.6341delC; 6 out 8 BRCA1/2 mutations). Interestingly, Chechen BRCA1 c.3629_3630delAG allele was not present among patients of Ingush ethnicity, despite these nations are believed to have common roots. BRCA2 Q3299X mutation was repeatedly observed across several ethnic groups. Patients from Kabardino-Balkaria had unusually high frequency of germ-line ATM truncating alleles (3/49, 6%); all 3 ATM mutations were represented by distinct ATM pathogenic variants. There were no instances of PALB2 germ-line mutations.
Conclusions
Genetic analysis of ovarian cancer patients is efficient in revealing ethnicity-specific BRCA1/2 mutations. Contribution of BRCA1/2 pathogenic alleles in OC morbidity is high across various ethnic groups. Founder BRCA1/2 alleles are characteristic for some but not all North Caucasus nations.
Legal entity responsible for the study
The authors.
Funding
This study has been supported by the Russian Science Foundation, grant 21-75-30015.
Disclosure
All authors have declared no conflicts of interest.
18P - The role of BYL719 in PIK3CA-mutated cervical cancer
- Giorgio Bogani (Milano, MI, Italy)
Abstract
Background
Advanced/recurrent cervical cancer has limited therapeutic options, with a median progression-free survival after the failure of systemic treatments ranging between 3.5 and 4.5 months. Here, we reported our preliminary experience in the use of BYL719 (alpelisib) in advanced/recurrent cervical cancer after failure of at least 2 lines of treatment.
Methods
This is a prospective trial testing the role of alpelisib in PIK3CA mutated patients. The Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (Italy) approved this prospective investigation (IRB number 20205720).
Results
From April 2020 to September 2020, 17 consecutive patients with recurrent cervical cancer had next-generation sequencing (NGS). Patients harboring PIK3CA mutation were included in the study. Overall, six patients were included in the study. All patients had been treated with at least 2 previous lines of systemic treatment: 3 patients received >2 prior lines of treatment in the recurrent or metastatic setting; 60% had received prior bevacizumab in combination with chemotherapy. All patients started alpelisib at the daily dosage of 300 mg. Investigator-assessed confirmed objective response rate (ORR) was 33%. The disease control rate (DCR) was 100%. According to RECIST 1.1, two patients had a partial response (PR), and four patients had stable disease (SD). No complete response was observed. The mean duration of response (DOR) was 11.5 (SD 3.75) months; five patients had PR lasting for >9 months. One patient stopped the treatment at 0.82 months due to the onset of a grade 2 adverse event (AE) (skin rash). Grade 3 treatment-related AEs included: lymphoedema (n=1, 20%) and rash (n=1, 20%). No treatment-related grade 4-5 AEs occurred.
Conclusions
Alpelisb seems associated with promising anti-tumor activity in cervical cancer patients harboring PIK3CA mutation. Further prospective trials are needed to assess the safety and effectiveness of alpelisib in PIK3CA-mutated pre-treated cervical cancer.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
38P - Impact of 1-year COVID-19 pandemic in patients with ovarian carcinoma treated with chemotherapy based on a GLOBAL DATA NETWORK
- Luis M. Manso Sanchez (Madrid, Spain)
Abstract
Background
The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Patients with ovarian cancer (OC) have been affected by a delay in diagnosis, surgery, and chemotherapy treatment (Jacome LS et al. Cancer Manag Res. 2021).
Methods
Here we have obtained a comprehensive overview of the impact of COVID-19 in patients with OC on a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCOs) all over the world. Descriptive statistics were used, and survival analyses were conducted using the Kaplan-Meier method.
Results
Through propensity score matched analyses of 74 global HCOs from 14 countries[AM1] we found that the number of new diagnoses of OC was reduced between the period from March 2020 to March 2021 (n=10.453) compared to 1-year prior to the COVID-19 pandemic (n=11.449), RR 0.91 [95%CI 0.88–0.9], p< 0.0001. SARS-CoV-2 infection in patients with OC treated with chemotherapy (n=710) was associated with worse overall survival than in patients without chemotherapy (n=1.770), HR 0.33 [95%CI 0.23-0.48], p< 0.0001.The risk of inpatient hospitalisation due to COVID-19 infection was higher in patients receiving chemotherapy vs no chemotherapy, RR 0.50 [95%CI 0.43-0.59], p < 0.0001. Overall, there was a very low rate of invasive mechanical ventilation utilization, with no differences in its use detected between those patients undergoing chemotherapy (n=24) and those who did not (n=18), RR 0.75 [95%CI 0.41-1.37), p=0.347.
Conclusions
This study highlights the necessity of extending preventive measures worldwide to protect vulnerable OC patients from SARSCoV-2 infection and promote intensive vaccination strategies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
3P - Identification of novel biomarkers of response to ATR inhibitors in ARID1A mutant ovarian clear cell carcinoma.
- James R. Stewart (London, United Kingdom)
Abstract
Background
Ovarian clear cell carcinoma (OCCC) is characterised by a high prevalence of ARID1A mutations and chemotherapy resistance. We previously found that loss of ARID1A causes ATR inhibitor (ATRi) sensitivity, which led to the phase II ATARI clinical trial (NCT04065269). We aim to identify novel genetic determinants of ATRi response in ARID1A-mutant OCCC.
Methods
A genome wide CRISPR knockout (CRISPRn) screen was performed in OCCC TOV21G cells. CRISPR prime gene-editing was used to introduce PPP2R1A p.R183 mutations. In vitro and in vivo ATRi sensitivity was assessed in PPP2R1A isogenic models. Cell cycle analysis was performed via flow cytometry. Phospho-proteomic profiling was performed using mass spectrometry.
Results
A CRISPRn screen in ARID1A mutant OCCC cells identified protein phosphatase 2 (PP2A) complex subunits as ATRi response genes. In OCCC, PPP2R1A missense mutations cause amino acid substitutions at residue p.R183. Characterisation of a cohort of OCCC primary tumours revealed a higher prevalence of structural subunit (PPP2R1A) mutations than previously reported (50%) which frequently co-occurred with ARID1A mutations. ARID1A-mutant OCCC cells with heterozygous PPP2R1A p.R183P or p.R183W mutations displayed enhanced ATRi sensitivity in vitro and in vivo. The most profound cell-cycle defect caused by PPP2R1A missense mutation was an ATRi-induced reduction in active S phase. ATRi exposure in PPP2R1A mutants increased 53BP1 bodies, a mark of residual DNA damage in mitosis. Phospho-proteomic profiling of PPP2R1A mutant OCCC cells revealed the selective increase in phosphorylation of Lysine Deficient Protein Kinase 1 (WNK1) following ATRi exposure, as well as increased phosphorylation of the WNK1 substrate Oxidative Stress Response Kinase 1 (OSR1). Depletion of WNK1 rescued ATRi sensitivity and S phase defects in PPP2R1A mutant cells suggesting a novel role for this kinase.
Conclusions
The ability of PPP2R1A missense mutations to enhance ATRi sensitivity in tumours cells with pre-existing ARID1A mutations suggests that the co-occurrence of these mutations may be better predictors of ATRi sensitivity than either mutation alone. Increased phosphorylation of WNK1 may drive ATRi sensitivity in PPP2R1A mutant cells.
Legal entity responsible for the study
The authors.
Funding
Cancer Research UK.
Disclosure
S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Genmabs; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck Sereno; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Oxcerna; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Shattuk Labs; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Immunogen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Mersana; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche. C. Lord: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: KGaG; Financial Interests, Institutional, Research Grant: Artios; Financial Interests, Personal, Advisory Board: Syncona; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal, Advisory Board: Gerson Lehrman; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Vertex; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Dark Blue Therapeutics; Financial Interests, Personal, Stocks/Shares: Tango; Financial Interests, Personal, Stocks/Shares: Ovibio; Financial Interests, Personal, Stocks/Shares: Enedra Tx; Financial Interests, Personal, Stocks/Shares: Hysplex; Financial Interests, Personal, Stocks/Shares: Tesselate. All other authors have declared no conflicts of interest.
19TiP - SGNTUC-019 Phase 2 basket study of tucatinib and trastuzumab in solid tumors with human epidermal growth factor receptor 2 alterations: uterine and cervical cancer cohorts
- David O'Malley (Columbus, OH, United States of America)
Abstract
Background
The prognosis of locally-advanced unresectable or metastatic (LA/M) cervical and uterine cancer remains poor, with HER2 alterations occurring in 0.5-21% of cervical cancers and 2-80% of uterine cancers, respectively. Tucatinib (TUC), a highly selective HER2 directed TKI, is approved in combination with trastuzumab (Tras) and capecitabine in multiple regions for HER2+ metastatic breast cancer and is being investigated in other HER2+ cancers, including LA/M cervical and uterine cancer. SGNTUC-019 (NCT04579380) is an open-label, international phase II basket study evaluating TUC and Tras in adult patients (pts) with LA/M HER2+ or HER2-mutated solid tumors.
Trial design
SGNTUC-019 will evaluate TUC and Tras in pts with previously treated, LA/M solid tumors that display HER2 overexpression/amplification or activating mutations, including HER2+ cervical and uterine cancer cohorts. Pts will receive TUC 300 mg PO BID and Tras 8 mg/kg IV on Cycle 1 Day 1 and 6 mg/kg q21 days from Cycle 2 Day 1. HER2+ cervical and uterine cancer cohorts will enroll 12 pts each with potential for expansion up to 30 pts. Pts with HER2-mutated cervical, uterine, and other gynecologic cancers may enroll in a pooled cohort of 30 pts with HER2-mutated solid tumor types. Eligible pts must have progressed on or after their last systemic therapy, with prior platinum-based chemotherapy ± bevacizumab required in pts with metastatic cervical cancer. Pts must have ECOG PS ≤1, adequate organ function, and have not received HER2-directed therapy; pts with uterine serous carcinoma may have received prior Tras. HER2 alterations can be demonstrated by HER2 overexpression/amplification in tumor tissue by prior IHC/ISH, or by HER2 amplification/mutation in a prior or on-study NGS assay of ctDNA or prior tissue NGS assay. The primary endpoint is confirmed ORR per investigator. DCR, DOR, PFS, OS, safety, and PK are secondary endpoints. Disease assessments per RECIST 1.1 will occur q6 weeks for 24 weeks, then q12 weeks. QoL will be evaluated q2 cycles using EQ-5D-5L. Enrollment is now open in Europe, the US, and Asia Pacific.
Clinical trial identification
NCT04579380.
Legal entity responsible for the study
Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA.
Funding
Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA.
Disclosure
D. O'Malley: Financial Interests, Personal and Institutional, Research Grant, Consultancy: AbbVie; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Agenus; Financial Interests, Personal, Other, Consultancy: Ambry; Financial Interests, Personal, Other, Consultancy: Arquer; Financial Interests, Personal and Institutional, Research Grant, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celsion; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Clovis; Financial Interests, Personal, Other, Consultancy: Corcept; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: Elevar; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Genentech/Roche; Financial Interests, Personal and Institutional, Research Grant, Consultancy: GOG Fnd; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Immunogen; Financial Interests, Personal and Institutional, Research Grant: Inc. Research; Financial Interests, Personal and Institutional, Research Grant: InVentiv Health; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Iovance; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Janssen; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Johnson & Johnson; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Mersana; Financial Interests, Personal, Other, Consultancy: Myriad; Financial Interests, Personal, Other, Consultancy: Novartis Novocure; Financial Interests, Personal, Other, Consultancy: Regeneron; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Rubis; Financial Interests, Personal, Other, Consultancy: SDPOnc; Financial Interests, Personal, Other, Consultancy: Seagen Inc.; Financial Interests, Personal, Research Grant, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Inxmed; Financial Interests, Personal and Institutional, Research Grant: Ajinomoto; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Cerulean; Financial Interests, Personal and Institutional, Research Grant: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: Ergomed; Financial Interests, Personal and Institutional, Research Grant: GenMab; Financial Interests, Personal and Institutional, Research Grant: Ludwig Cancer Research; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: New Mexico CCA; Financial Interests, Personal and Institutional, Research Grant: Novocure; Financial Interests, Personal and Institutional, Research Grant: PRA Int'l; Financial Interests, Personal and Institutional, Research Grant: Regeneron; Financial Interests, Personal and Institutional, Research Grant: SDPOnc; Financial Interests, Personal and Institutional, Research Grant: Seagen Inc.; Financial Interests, Personal and Institutional, Research Grant: Serono; Financial Interests, Personal and Institutional, Research Grant: Stemcentrx; Financial Interests, Personal and Institutional, Research Grant: Tarveda; Financial Interests, Personal and Institutional, Research Grant: Tesaro/GSK; Financial Interests, Personal and Institutional, Research Grant: Tracon Pharma; Financial Interests, Personal and Institutional, Research Grant: VentiRx; Financial Interests, Personal and Institutional, Research Grant: Yale University; Financial Interests, Personal, Invited Speaker: Sorrento; Financial Interests, Personal, Other, Consultancy: Takeda; Financial Interests, Personal, Other, Consultancy: Tesaro/GSK; Financial Interests, Personal, Other, Consultancy: Toray. F.J. Jin: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Ownership Interest: Merck; Financial Interests, Personal, Other, Travel Expenses: Merck. J.D. Ramos: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc. Q. Tan: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc.; Financial Interests, Personal, Other, Travel Expenses: Seagen Inc. B.J. Monk: Financial Interests, Personal, Other, Consultant: Agenus; Financial Interests, Personal, Other, Consultant: Akeso Bio; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, Consultant: Aravive; Financial Interests, Personal, Other, Speaker/Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Bayer; Financial Interests, Personal, Other, Speaker/Consultant: Clovis; Financial Interests, Personal, Other, Speaker/Consultant: Eisai; Financial Interests, Personal, Other, Consultant: Elevar; Financial Interests, Personal, Other, Consultant: EMD Merck; Financial Interests, Personal, Other, Consultant: Genmab/Seagen; Financial Interests, Personal, Other, Consultant: GOG Foundation; Financial Interests, Personal, Other, Consultant: Gradalis; Financial Interests, Personal, Other, Consultant: ImmunoGen; Financial Interests, Personal, Other, Consultant: Karyopharm; Financial Interests, Personal, Other, Consultant: Iovance; Financial Interests, Personal, Other, Consultant: Macrogenics; Financial Interests, Personal, Other, Speaker/Consultant: Merck; Financial Interests, Personal, Other, Consultant: Mersana; Financial Interests, Personal, Other, Honorarium: Novartis; Financial Interests, Personal, Other, Consultant: Novocure; Financial Interests, Personal, Other, Consultant: Myriad; Financial Interests, Personal, Other, Consultant: OncoC4; Financial Interests, Personal, Other, Consultant: Pieris; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Puma; Financial Interests, Personal, Other, Consultant: Regeneron; Financial Interests, Personal, Other, Speaker/Consultant: Roche/Genentech; Financial Interests, Personal, Other, Consultant: Sorrento; Financial Interests, Personal, Other, Speaker/Consultant: Tesaro/GSK; Financial Interests, Personal, Other, Consultant & Investigator: US Oncology Research; Financial Interests, Personal, Other, Consultant: VBL.
39P - Longitudinal Increases in Albumin-Adjusted Serum Calcium Predict Ovarian Cancer
- Gary Schwartz (Grand Forks, ND, ND, United States of America)
Abstract
Background
Screening methods for ovarian cancer are urgently needed. Previously, we showed that women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin (Schwartz et al, 2020, Gynecol Oncol 2020:159:264-269). These changes could be useful in screening. We asked, prior to their diagnosis, are women with ovarian cancer more likely to show a positive slope in their in albumin-adjusted serum calcium (a-asc)?
Methods
This is a population-based case-control study based in Sioux Falls, SD. Cases were women with epithelial ovarian cancer. Controls are women without a diagnosis of cancer. Patients with a history of cancer and/or parathyroid disease were excluded. Data are from patients’ Comprehensive Metabolic Panels (CMPs). We calculated albumin-adjusted serum calcium (a-asc) and estimated regression equations of each woman’s a-asc from pre-diagnosis to diagnosis. Data were analyzed by multiple regression, ANCOVA and logistic regression.
Results
We studied 124 cases and 98 controls. Cases were significantly older than controls (64.7 12.9 SD, vs. 41.0 16.8 years). For controls, the first and last a-asc was 9.23 mg/dL, for a slope of 0. For cases, the first and last values of a-asc were 9.28 and 9.37 mg/dL, for a slope of 0.04 mg/dl per year (P<0.001). The probability of cancer for a 0.04 mg/dL/year increase in a-asc increased with age until age 70 and showed a significant dose-response. The Odd Ratio (OR) of ovarian cancer for a 65 yr old woman with a 0.06 mg/dL increase/year was ∼3.0; the OR for a 1 mg/dl increase/year was ∼10. This effect was also seen for early stage tumors and persisted after age-adjustment.
Conclusions
In health, serum calcium levels are tightly regulated and the “expected” slope of a-asc is zero. A significant positive slope of a-asc in women with ovarian cancer, if confirmed by future studies, suggests that an increase in the slope a-asc could help identify women with undiagnosed ovarian cancer. Increases in a-asc were often small and could be easily overlooked. However, a computer algorithm could calculate the slope from patients’ annual records. Women with rising a-asc could be candidates for increased medical surveillance (e.g., transvaginal ultrasonography).
Legal entity responsible for the study
The authors.
Funding
This research was funded by grants from the University of North Dakota School of Medicine & Health Sciences, the Great Plains IDeA-CTR and the Coverys Community HealthCare Foundation (to GGS).
Disclosure
All authors have declared no conflicts of interest.