bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of the anti–PD-L1 monoclonal antibody socazolimab for recurrent or metastatic cervical cancer: Results from the phase I dose-escalation and expansion study.
Authors: An Jusheng , Guiling Li , Tang Jie , Li Benjamin Xiaoyi , Xiong Hui Hua , Qiu Hui , Luo Lin , Wang Li , Wang Danbo , Zhou Qi , Xu Qin , Song Hong Lin , Zhang Yun Yan , Zhang Hong Ping , Ng Rachel , Zhao Zewei , Dai Xiang Rong , Li Yu Jie , Sun Yuanjue , Wu Lingying 
Published: June 2022

5526 Background: The study (NCT03676959) is an open-label, phase I study investigating the safety and efficacy of the recombinant, fully human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody socazolimab for recurrent or metastatic cervical cancer. 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. Primary endpoints of the dose-expansion phase were safety and overall response rate (ORR) of the 5mg/kg dose. Efficacy was assessed by a third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as the evaluation standard. Pharmacokinetics and pharmacodynamics were also studied. Results: One hundred four patients were enrolled. Twelve patients were included in the dose-escalation phase, with one complete and two partial responses in the 5mg/kg treatment group. Ninety-two patients (5mg/kg) were enrolled in the dose-expansion phase, with 54 patients (59.3%) expressing baseline PD-L1-positive tumors. ORR was 15.4% (95% CI, 8.7 to 24.5%). Median PFS was 4.44 months (95% CI, 2.37 to 5.75 months), and the median OS was 14.72 months (95% CI, 9.59 to NE months). ORRs for PD-L1-positive and PD-L1-negative patients were 16.7% and 17.9%, respectively. Treatment-related grade 3 to 4 adverse events occurred in 7.7% of patients. No treatment-related deaths had occurred. Conclusions: Our study demonstrates that socazolimab has remarkable 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 monoclonal antibodies. Clinical trial information: NCT03676959. [Table: see text]
SPECT-defined, active bone marrow–sparing, volumetric-modulated arc therapy reduces the incidence of acute hematologic toxicity in patients with locally advanced cervical cancer who receive chemoradiotherapy.
Authors: Wang Shan Bing , Liu JiaPei , Jia Yuming , Lei Kaijian 
Published: June 2022

5527 Background: Acute haematologic toxicity is the most common side effect of chemoradiotherapy in patients with locally advanced cervical cancer.We are aim to test the efficacy of defined active bone marrow sparing volumetric-modulated arc therapy reduces grade 3 or higher (grade 3+) acute haematologic toxicity for patients with locally advanced cervical cancer treated with chemoradiotherapy. Methods: This was a prospective, single-center, open label, randomized clinical trial that enrolled locally advanced cervical cancer.Patients were randomized to 99mTc sulfur colloid SPECT-defined active bone marrow sparing volumetric-modulated arc therapy group (ABMS group) or control group.The control group received weekly cisplatin concurrently with volumetric-modulated arc therapy(VMAT),followed by high-dose-rate intracavitary brachytherapy. The active bone marrow sparing volumetric-modulated arc therapy group additionally received 99mTc sulfur colloid SPECT-defined active bone marrow dose constrain. The primary endpoint was the incidence of grade 3 or higher (grade 3+) acute haematologic toxicity. Secondary objectives included acute gastrointestinal toxicity, planning Target Volume (PTV) coverage and dosimetric parameters of organs at risk(OARs). Results: A total of 148 patients with Federation of Gynaecology and Obstetrics(FIGO) stage IB-IIIB fromJanuary 2017 to April 2019 were randomized，and 146 were treated(74 in ABMS group and 74 in control group). The median follow-up was 20.0 months.The incidence of grade 3 or higher (grade 3+) acute haematologic toxicity in the ABMS group was 29.7%,significantly lower than the 48.6% incidence in the control group(p = 0.03).The incidence of grade 3+ neutropenia (ABMS group：20.3%,control group:36.5%;p = 0.04), Grade 3+ leukopenia (ABMS group：25.7%,control group:44.6%;p = 0.02) and Grade 3+ lymphopenia (ABMS group：4.1%,control group:14.9%;p = 0.04) were significantly differences between the two group.The were no differences in Grade 3+ anemia (ABMS group：1.4%,control group:5.5%;p = 0.37) and Grade 3+ acute gastrointestinal toxicity(ABMS group：1.4%,control group:1.4%;p = 1.00) between the two group.The number of patients completing five cycles of cisplatin in the ABMS group was 88.5%,,significantly higher than the 75% in the control group(p = 0.02).There were no differences in PTV coverage and dosimetric parameters of OARs between the two group. Conclusions: SPECT-defined active bone marrow sparing VMAT signifificantly reduced grade 3+ acute haematologic toxicity,and improved chemotherapy delivery compared with control group. Clinical trial information: ChiCTR-IOR-16010214.
Overall survival results from a phase II trial of anlotinib plus sintilimab in patients with recurrent advanced cervical cancer.
Authors: Xu Qin , Chen Chuan-ben , Sun Yang , Huang Zhangzhou , Lin Yibin , Liu Jing , Li Li , Li Zirong , Pan Junping , Chen Ying 
Published: June 2022

5536 Background: The anlotinib (a novel multi-target TKI, inhibiting tumor angiogenesis and proliferative signaling) plus sintilimab (an antibody against PD-1) in patients with advanced cervical cancer trial was a multicenter, single-arm, phase II study (ChiCTR1900023015) that showed promising activity. The results of this trial have been previously reported and here we present updated survival data after a median follow-up of 13.0 months. Methods: Pts who have received at least once platinum-based chemotherapy, recurrent advanced cervical cancer, PD-L1 for CPS≥1, ECOG 0-1 were considered eligible for enrollment. Anlotinib was taken orally (10mg, qd, d1-14, 21 days per cycle), and sintilimab was administered intravenously (200mg, q3w, d1). The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS), safety and biomarkers. Results: Between December 2019 and December 2020, 42 patients with a median age of 53 years (range 36 to 67 years) were enrolled and received study treatment (ITT population and safety population). The data cutoff date was February 10, 2022. The patients were followed up for median duration of 13.0 months (range 0.03 to 24.8 months). In the ITT population, 2 (4.8%) patients achieved CR and 21 (50%) attained PR, the confirmed ORR was 54.8% (95% CI 38.7% to 70.2%). Fourteen (33.3%) patients had SD and the DCR was 88.1% (95% CI 74.4% to 96.0%). In the efficacy-evaluable patients (n = 39), the ORR was 59% (95% CI 42.1% to 74.4%) and the DCR was 94.9% (95% CI 82.7% to 99.4%). The median PFS was 9.46 months (95% CI 8.2 to 11.9) and the 6-month PFS rate was 73.4% (95% CI 60.6% to 89.0%). OS events occurred in 18 patients (42.9%). The median OS was 17.4 months (95% CI 12.4 to not reached). The 12-month OS rate and 24-month OS were 71.8% (95% CI 59.0% to 87.4%) and 49.1% (95% CI 34.5% to 69.9%), respectively. Conclusions: Anlotinib plus sintilimab showed a long-term survival benefit for patients with recurrent advanced cervical cancer. Additional investigations in larger randomized controlled trials are warranted in the future. Clinical trial information: ChiCTR1900023015.
Phase Ib INEOV neoadjuvant trial of durvalumab +/- tremelimumab with platinum chemotherapy for patients (pts) with unresectable ovarian cancer (OC): Final complete resection and pathological response rates.
Authors: Leary Alexandra , De La Motte Rouge Thibault , Lortholary Alain , Asselain Bernard , Alexandre Jerome , Floquet Anne , Savoye Aude Marie , Delanoy Nicolas , Gavoille Céline , You Benoit , D'hondt Veronique , Grenier Julien , Genestie Catherine , Chardin Laure , Pujade-Lauraine Eric ,   GINECO (Groupe d’Investigateurs Nationaux pour l’Etude des Cancers de l’Ovaire et du sein)
Published: June 2022

5557 Background: We have shown that neoadjuvant carboplatin and paclitaxel (NACP) increased tumor infiltrating lymphocytes and PDL1 expression in OC pts. INEOV evaluated NACP with durvalumab (D) +/- tremelimumab (T) in pts with unresectable OC. We previously reported that NACP with D+/-T was feasible and safe but the addition of T did not improve interval debulking surgery (IDS) rates after 3 cycles (C3) (ESMO 2021). Here we provide an update with longer follow up including data on delayed IDS performed after 6 cycles of neoadjuvant treatment. Key secondary endpoints include complete resection (CC0) and complete pathological response rates. Methods: Pts with stage IIIC/IV OC were randomized to NACP + D (1125mg) alone (arm A) or with T (75mg once at C2) (arm B). Interval debulking surgery (IDS) was planned after C3, or delayed after C6. Pts in arm A not operable after C3 crossed over to arm B, pts in arm B crossed over to standard of care (SOC). Pts were assessed for delayed IDS after C6. Complete pathological response (pCR) was defined as no residual tumor cells found on any surgical specimens, or no residual tumor cells on any samples outside the ovary at IDS. Results: Sixty four (N = 64) of 66 pts (IIIC/IV: 70%/30%) randomized were evaluable. After C3, 66% (21/32) of pts in arm A and 59% (19/32) in arm B had IDS. The 11 pts in arm A not candidate for IDS after C3 crossed over to arm B until C6 and 5/11 benefited from delayed IDS. The 13 pts in arm B inoperable at C3 went on to receive SOC (NACP +/- bevacizumab), and 5/13 became eligible for delayed IDS after C6. Overall, IDS was performed in 50 of 64 evaluable pts, and most (45/50) achieved macroscopically complete resection (CC0), so that the overall CC0 rate was 70% (45/64), with no significant difference between arms (CC0 = 75% vs 65% in arm A vs B). Among the 50 pts who had IDS, complete pathological responses were observed in 18% of pts. Conclusions: Taking into account the whole treatment strategy including delayed IDS after 6 cycles of neoadjuvant treatment, we have shown that neoadjuvant CP with D+/- T results in encouraging CC0 (70%) and pCR (18%) rates. However there was no apparent benefit to the addition of T to D. Studies are ongoing to describe the immune features predictive of pCR as well as the impact of treatment on the immune microenvironment. Clinical trial information: NCT03249142.
Identifying disparities in gynecologic cancer: Results and analysis from a patient preference survey.
Authors: Chapman-Davis Eloise , Halla Kimberly J. , Westin Shannon Neville , Salani Ritu , Constanzo Jerfiz D. , Quill Timothy A. , Burn Kathryn , Secord Angeles Alvarez 
Published: June 2022

5561 Background: Health disparities exist in gynecologic cancers, with data revealing lower survival among certain racial/ethnic groups. Studies suggest underrepresented patients of color with gynecologic cancers may not receive guideline-concordant care to adequately manage their disease, including molecular testing. We conducted a patient preferences survey evaluating treatment choices and provider interactions influencing adherence to guideline-based care. Methods: From July 7 to August 18, 2021, a survey was sent to women with gynecologic cancers who participate in the SMART Patients advocacy group. Survey questions covered topics of preparedness to discuss care with provider, biomarker testing specific to gynecologic tumor type, patients’ considerations informing treatment choices, and confidence to work with providers to improve their clinical and survival outcomes. Information regarding cancer diagnosis, stage, race, ethnicity, treatment, and genetic testing was obtained. Survey responses between non-Hispanic White patients (W) versus non-White (NW) underrepresented patients of color were compared and analyzed using descriptive statistics. Results: A total of 89 women with gynecologic cancers (67% ovarian, fallopian tube, and peritoneal; 21% endometrial; 9% vulvar or vaginal; and 2% cervical) participated in the patient survey. Amongst responders, 55% had localized disease while 36% indicated they had metastatic disease, and 9% did not know. Overall, 86.5% were W and 13.5% were NW (Asian, Black/African American, Native American or Pacific Islander, Hispanic, or mixed race). A higher proportion of NW compared to W patients said they were not at all prepared to discuss cost of treatment (18.2% vs 9.5%), treatment options (12.5% vs 4.5%), and side effects of treatment (20% vs 0%) with their provider; 31% of W patients discussed genetic testing and received resources from their provider compared with only 16.7% of NW patients, and a higher proportion of NW compared to W patients (37.5% vs 28.1%) indicated they were not confident in their ability to work with providers to improve their cancer treatment outcome. Conclusions: While a limitation of this study was low participation from diverse populations, the findings indicate that underrepresented NW patients felt less prepared to discuss treatment-related issues compared to W patients. Moreover, a large proportion of all patients with OC were not informed and/or aware about genetic testing, and approximately a third of participants were not confident in their ability to interact with provider to improve their outcomes. The results highlight opportunities to enhance health care provider education and community outreach to reduce gaps in care delivery.
Pharmacokinetic and pharmacodynamic analysis of adavosertib in advanced ovarian cancer.
Authors: Oza Amit M. , Lheureux Stephanie , Madariaga Ainhoa , Cristea Mihaela C. , Mantia-Smaldone Gina , Olawaiye Alexander , Ellard Susan , Weberpals Johanne I , Wahner Hendrickson Andrea Elisabeth , Fleming Gini F. , Welch Stephen , Dhani Neesha C. , Speers Vanessa , Bowering Valerie , Wang Lisa , Zhang Wenjiang , Chen Eric Xueyu 
Published: June 2022

5579 Background: Adavosertib (AZD-1775) is a potent small molecule inhibitor of Wee-1, currently in clinical development. In a double-blind, placebo-controlled, phase 2 trial (NCT02151292), adavosertib and gemcitabine significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with recurrent platinum-resistant or platinum-refractory high grade serous ovarian cancer (HGSOV) compared to gemcitabine alone. We investigated whether plasma and intra-tumoral adavosertib concentrations correlated with survival in these patients. Methods: Adavosertib was administered orally on Days 1, 2, 8, 9, 15 and 16 at 175 mg per day, and gemcitabine was administered on Days 1, 8 and 15 at 1000 mg/m2 every 28 days. Serial blood samples were collected on Day 1 of cycle 1 after adavosertib administration. Tumor biopsies were taken 1-2 weeks after initiation of study treatments. Plasma and tumor adavosertib concentrations were determined using validated HPLC-MS/MS. Patients were divided into groups with plasma or tumor adavosertib concentrations above or below the biologically active concentration (BAC) of 125 ng/ml (Leijen et al, J Clin Onco 2016). Survival was described using the Kaplan-Meier method. Results: Among 61 HGSOV patients who received adavosertib, plasma samples were available in 47, and tumor samples were available in 31 patients. Among 25 non-HGSOV patients (exploratory cohort), plasma and tumor samples were available in 21 and 17 patients respectively. The mean maximum adavosertib concentration (Cmax) was 355.3 ± 120.9 ng/ml and 358.6 ± 117.9 ng/ml respectively. Cmax was above BAC in all patients. The mean tumor adavosertib concentration was 609.2 ± 1129.2 ng/ml (range: 0.47 – 5501 ng/ml) for HGSOV patients, and 964.2 ± 1611.2 ng/ml (range: 0.22 – 6116 ng/ml) for non-HGSOV patients. There was no correlation between Cmax and tumor adavosertib concentrations. In HGSOV, the median PFS was 5.8 months for patients with tumor concentrations above BAC, and 3.5 months for those with tumor concentrations below BAC (Hazard ratio (HR): 0.46, 95% confidence interval: 0.19 – 1.14, p = 0.06). No difference in PFS was seen in non-HGSOV patients according to tumor adavosertib concentration. Tumor adavosertib concentration did not correlate with OS. Conclusions: Although Cmax was above BAC in all patients, there was a high variability in tumor adavosertib concentrations. In HGSOV, higher tumor adavosertib concentration was associated with a trend towards improved PFS, but not OS. Our results indicate that the current adavosertib dosing regimen may not produce the desired concentrations in tumors for some patients, and further optimization may be needed.
Real-world clinical outcomes in patients with local/regional HER2-low breast cancer: An NCDB analysis.
Authors: Jiang Changchuan , Perimbeti Stuthi , Deng Lei , Wang Qian , Gandhi Shipra , Shapiro Charles L. 
Published: June 2022

558 Background: The development of novel anti-HER2 drugs opens new treatment options, including women with lower expression of HER2. This study aimed to compare local/regional HER2-low and HER2-0 breast cancer outcomes in the real world. Methods: Women diagnosed between 2010 and 2017 with clinical stage I-III breast cancers with low HER2 expression or HER2-zero (0) expression were identified in the National Cancer Database (NCDB), a nationwide oncology outcomes database in the United States. HER2-Low was defined as IHC1+ or 2+/ISH negative, whereas HER2-zero was IHC-0. The primary outcome was overall survival (OS). We performed a multivariable Cox regression model to estimate hazard ratios and adjusted for the following factors: age, race/ethnicity, education, insurance, comorbidities, grade, stage, lymph nodes, type of surgery, the type of cancer center, and if any chemotherapy, any hormonal therapy, and any adjuvant radiation in the first treatment course. Stratification factors were hormone receptor status. Subgroup analyses for those who received neoadjuvant (NAC), adjuvant (AC), and no chemotherapy were performed, and the pathologic complete response (pCR) rates in NAC groups were estimated. Results: 376,199 (68%) women with HER2-low tumors and 177,298 (32%) with HER2-0 tumors were analyzed. 336,147 (89%) of the HER2-low tumors and 141,528 (79%) of the HER2-0 tumors were HR-positive. Low HER2 expression was associated with longer OS in both HR-positive (adjusted Hazard Ratio (aHR): 0.94, 95%CI 0.93-0.96, p<0.001) and HR-negative diseases (aHR: 0.88, 95%CI 0.85-0.91, p<0.001). HR-positive, HER2-low tumors had statistically significantly better survival than HR-positive, HER2-0 tumors in NAC (aHR 0.84, 95%CI 0.79-0.90, p<0.001) and AC (aHR 0.90, 95%CI 0.85-0.94, p<0.001) groups, but not in the no-chemo group (aHR 1.02, 95%CI 1.00-1.05, p=0.09, p interaction<0.001). In contrast, HR negative, HER2-low tumors had better OS than HR negative, HER2-0 tumors in all subgroups, regardless of receipt or timing of chemotherapy (NAC aHR 0.88, 95%CI 0.83-0.94, p<0.001, AC aHR 0.86, 95%CI 0.81-0.92, p<0.001, No chemo aHR 0.93, 95%CI 0.87-0.99, p=0.03, p interaction=0.06). In NAC groups, HER2-low expression was linked to lower pCR rates in both HR-positive (8.9% vs. 11.2%, p<0.001) and HR-negative (31.2% vs. 34.1%, p<0.001). Conclusions: Local/regional HER2-low breast cancer has better survival than HER2-0 breast cancer, irrespective of its hormone receptor status. The survival advantage was observed in HR-negative disease and only with receipt of chemotherapy in HR-positive breast cancer. Specific therapies, such as trastuzumab deruxtecan, have activity in HER2-low breast cancers, and other therapeutics for HER-2 low diseases should be sought.
Stage 1 results of BrUOG 354: A randomized phase II trial of nivolumab alone or in combination with ipilimumab for people with ovarian and other extra-renal clear cell carcinomas (NCT03355976).
Authors: Dizon Don S. , Robison Katina , MacLaughlan David Shannon Diane , Machan Jason T , Hadfield Matthew James , Marks Eric I , Chudasama Rani , Evans Tarra , Lopresti Mary Lorraine , Safran Emma , Kastura Michaela , Hassinger Faith , Sturtevant Ashlee , Wood Roxanne , Wright Alexi A. , Strenger Rochelle , Matulonis Ursula A. , Bandera Christina , Campos Susana M. , Birrer Michael J. 
Published: June 2022

5598 Background: Clear Cell Carcinoma (CCC) outside the kidney is a rare tumor that can arise from multiple organs, including the ovary, endometrium and cervix. Extra-renal CCC is chemoresistant and has a poor prognosis. Data suggest that CCC of the gynecologic tract resembles the genomic profile of Renal Cell Carcinoma (RCC), which is responsive to immune checkpoint inhibition (ICI) therapy. We are conducting a two-stage phase 2 trial evaluating immunotherapy for extra-renal CCC. The primary objective is to assess overall rate of response (ORR); Progression-Free (PFS), Overall Survival (OS), and correlative biomarker studies are secondary. Here we present the results of Stage 1. Methods: This is a randomized two-stage non-comparative phase II study evaluating nivolumab (240mg IV every two weeks) alone (N) and in combination with ipilimumab (1mg/kg every six weeks, [N+I]) in patients with relapsed extra-renal CCC after at least one prior chemotherapy (no prior ICI), and measurable disease. Treatment was continued until disease progression or unacceptable toxicity. Stage 1 of this trial called for up to 30 volunteers (15 per arm) after which the study was closed. Consideration to reopen to stage 2 called for two or more responses in either arm. Here we present the completion of Stage 1; the release of results was approved by Brown University Oncology Group (BrUOG) Data Safety and Monitoring Committee. Results: Between July 2018 and October 2021, 30 patients were enrolled and 29 were treated (Table). The majority (83%) had CCC of the ovary (n=24). The ORR with N and N+I was 14.2 and 26.7%, respectively. The 6 month PFS rate was 19.1 and 43.8%; median PFS was 2.7 (95%CI 1.3-5.1) and 5.1 months (95%CI 0.9-NR), respectively. Grade ≥3 treatment-related toxicities occurred in 4 (28.6%) on N and 5 (33.3%) on N+I. There were no treatment-related deaths and no new safety signals. One volunteer enrolled on N+I stopped treatment after two years and remains in CR to date. Conclusions: Although sufficient activity was seen in CCC in both arms, the single-agent activity of N is similar to published reports in platinum-resistant epithelial ovarian cancer and decision made not to pursue it further. However, the combination of ipilimumab and nivolumab warrants additional investigation, and the second stage of this study will enroll 14 more patients to receive N+I. Clinical trial information: NCT03355976. [Table: see text]