bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dostarlimab for primary advanced or recurrent (A/R) endometrial cancer (EC): Outcomes by blinded independent central review (BICR) of the RUBY trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).
Authors: Powell Matthew A. , Hietanen Sakari , Coleman Robert L. , Monk Bradley J. , Zub Oleksandr , O'Malley David M. , Gilbert Lucy , Podzielinski Iwona , Angioli Roberto , Chase Dana Meredith , Bauerschlag Dirk , Black Destin , Thijs Annemarie , Sharma Sudarshan , Gold Michael A. , Ring Kari L , He Zangdong , Stevens Shadi , Slomovitz Brian M. , Mirza Mansoor R. 
Published: June 2023

5503 Background: RUBY (NCT03981796) evaluated the efficacy and safety of the anti–programmed death 1 (PD-1) dostarlimab + standard of care (SOC) carboplatin paclitaxel (CP) versus CP alone in A/R EC. The primary endpoint of PFS by investigator assessment (INV) per RECIST v1.1 was significantly longer with dostarlimab+CP than placebo (PBO)+CP in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H; HR 0.28; 95% CI 0.162–0.495) and overall populations (HR 0.64, 95% CI 0.507–0.800). Here we present secondary efficacy endpoints by BICR. Methods: RUBY is a phase 3, global, randomized, double-blind, multicenter, PBO-controlled study. Patients (pts) with primary advanced stage III or IV or first recurrent EC were randomized 1:1 to receive dostarlimab 500 mg, or PBO, plus carboplatin AUC 5 and paclitaxel 175 mg/m2 Q3W (6 cycles), followed by dostarlimab 1000 mg, or PBO, monotherapy Q6W for up to 3 y. Secondary endpoints by BICR assessment per RECIST v1.1 were PFS, ORR, DOR, and DCR in the overall and dMMR/MSI-H populations. Results: 494 pts were randomized (245:dostarlimab+CP; 249:PBO+CP); 47.8% had recurrent disease, 18.6% and 33.6% had primary stage III and IV disease, respectively. PFS by BICR was longer with dostarlimab+CP than PBO+CP in the dMMR/MSI-H (HR 0.29; 95% CI 0.158–0.543) and overall populations (HR 0.66; 95% CI 0.517–0.853; Table). Consistent benefits were seen with dostarlimab+CP for ORR, DCR, and DOR by BICR in the dMMR/MSI-H and overall populations (Table). Safety was previously reported. Conclusions: Dostarlimab+CP showed clinically meaningful improvement in BICR-assessed PFS in the dMMR/MSI-H and overall populations compared with CP alone. The HRs for PFS per BICR and per INV were consistent, which supports the reliability of PFS by INV in EC trials. Benefits were seen in all BICR-assessed endpoints, which were consistent with INV. Dostarlimab+CP represents a new SOC for pts with primary A/R EC. Clinical trial information: NCT03981796 . [Table: see text]
Randomized controlled phase III trial of weekly paclitaxel ± ofranergene obadenovec (VB-111) for platinum-resistant ovarian cancer (OVAL Study/GOG 3018).
Authors: Arend Rebecca Christian , Monk Bradley J. , Shapira-Frommer Ronnie , Secord Angeles Alvarez , Herzog Thomas J. , Tewari Krishnansu Sujata , Ledermann Jonathan A. , Rachmilewitz Minei Tamar , Buyse Marc E. , Haggerty Ashley , Alvarez Edwin A , Amit Amnon , Muller Carolyn , Casado Herraez Antonio , Holman Laura L. , Cohen Joshua , Huang Marilyn , Yachnin Adelya , Harats Dror , Penson Richard T. 
Published: June 2023

5505 Background: Ofranergene obadenovec (ofra-vec, VB-111) is a nonreplicating adenoviral vector with a murine pro-endothelin 1 (PPE-1-3X) promoter and pro-apoptotic Fas-tumor necrosis factor receptor 1 (TNFR1) chimeric transgene thought to have a dual mechanism of action: vascular disruption and immune activation. Methods: This is a randomized, placebo-controlled, double-blind, multi-center randomized phase III trial (ClinicalTrials.gov identifier: NCT03398655) of ofranergene obadenovec combined with paclitaxel vs paclitaxel with placebo for the treatment of patients with recurrent platinum resistant ovarian cancer (PROC). Patients were randomly assigned 1:1 to receive IV VB-111 1x1013 viral particles (VPs) every 8 weeks with weekly IV paclitaxel 80 mg/m2 or placebo with paclitaxel until disease progression. The dual primary endpoints were overall survival (OS) and progression free survival (PFS) as assessed by Blinded Independent Central Review (BICR). Results: Between December 2017 and March 2022, 409 patients were randomized at 86 clinical sites in US, Israel, Spain, Poland and Japan. The median PFS was 5.29 months in the VB-111 arm and 5.36 months in the control arm; hazard ratio (HR) 1.03 (CI: 0.83-1.29, p = 0.7823), and median OS with was 13.37 months vs. 13.14 months HR 0.97 (CI: 0.75–1.27 p = 0.8440). Objective response rates (ORR) were similar in both arms: RECIST 1.1 ORR was 28.9% with VB-111 vs. 29.6% with control (CA-125 ORR 41.1% vs 49.4%). In both treatment arms response to CA-125 was a substantial prognostic factor for both PFS and OS. In the VB-111 arm, the HR in CA-125 responders compared to non-responders was for PFS HR 0.2428 (CI: 0.1642-0.3588), and for OS HR 0.3343 (CI: 0.2134-0.5238). Safety profile was consistent with the known safety profile of ofra-vec and was characterized by common transient flu like symptoms such as fever and chills. Conclusions: The addition of ofranergene obadenovec to paclitaxel did not improve PFS or OS. Clinical trial information: NCT03398655 .
Luveltamab tazevibulin (STRO-002), an anti-folate receptor alpha (FolRα) antibody drug conjugate (ADC), safety and efficacy in a broad distribution of FolRα expression in patients with recurrent epithelial ovarian cancer (OC): Update of STRO-002-GM1 phase 1 dose expansion cohort.
Authors: Oaknin Ana , Fariñas-Madrid Lorena , García-Duran Carmen , Martin Lainie P. , O'Malley David M. , Schilder Russell J. , Uyar Denise , Moroney John William , Diaz John Paul , Spira Alexander I. , Garcia-Donas Jesus , Palumbo Michael , Dokainish Hatem , Liu Lin , Berman Craig Jerome , Naumann R. Wendel 
Published: June 2023

5508 Background: Luveltamab tazevibulin (luvelta) is a novel FolRα-targeting ADC with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR of 4) that induces cytotoxic and immunologic cell death. Using site-specific conjugation technology, luvelta is designed to target a broad range of FolRα expressing OC. STRO-002-GM1 is a global phase 1 study evaluating luvelta in patients with relapsed OC. We provide updated data from the initial ovarian expansion cohort. Methods: The study enrolled advanced OC pts who had progressive platinum resistant (PROC) after 1-3 prior lines or platinum sensitive disease after 2-3 prior lines of platinum chemotherapy. Pts were randomized 1:1 to received luveltamab at 4.3 or 5.2 mg/kg given IV every 3 weeks until disease progression. Prophylactic corticosteroid eyedrops were not required/administered. FolRα expression was not required for study entry but was analyzed retrospectively in archival tissue using the FOLR1 IHC assay (Ventana Medical Systems). The scoring paradigm assessed percentage of cells with any intensity expression (TPS). TPS >25% was selected for further analysis. Results: 44 pts were enrolled (23 pts at 4.3 mg/kg and 21 pts at 5.2 mg/kg). For pts with a TPS >25% (n=35), the median prior lines of therapy was 2.5 (range 1-3), 69% had prior bevacizumab treatment, and 83% prior PARP inhibitor treatment. Investigator assessed efficacy data for pts with a TPS >25% are presented in the table. The most common grade ≥ 3 treatment emergent adverse events (TEAEs) included neutropenia (70.5%), arthralgia (18.2%), and anemia (13.6%). G3/4 neutropenia had a higher incidence at 5.2 mg/kg than 4.3 mg/kg (76% vs 65%); most notable for G4 neutropenia (52% vs 22%). 1 pt at each dose level had febrile neutropenia. TEAEs led to dose delay in 80% of pts with a higher incidence at 5.2 mg/kg (95% vs. 65%). TEAEs led to dose reduction in 61% of pts with a higher incidence at 5.2 mg/kg (76% vs. 48%). 1 pt had a G5 sepsis with G4 neutropenia. Neutropenia, arthralgia and anemia were managed with standard medical treatment and dose reductions. Conclusions: These dose expansion data confirm activity of luvelta at starting doses ranging from 4.3-5.2 mg/kg in recurrent OC with FolRα expression as low as TPS>25% and supports further clinical study in this population. The global phase 2/3 REFRaME registration study will evaluate luvelta in PROC pts with TPS >25%. Clinical trial information: NCT03748186 . [Table: see text]
Final survival analysis of the phase III OVHIPEC-1 trial of hyperthermic intraperitoneal chemotherapy in ovarian cancer after ten year follow-up.
Authors: Aronson Lot , Lopez-Yurda Marta I. , Koole Simone N , Schagen van Leeuwen Jules H , Schreuder Henk , Hermans Ralph , de Hingh Ignace H.J.T. , Van Gent Mignon D.J.M. , Arts Henriëtte J.G. , van Ham Maaike , Van Dam Peter , Vuylsteke Peter , Aalbers Arend , Verwaal Victor , Van de Vijver Koen , Aaronson Neil K , Sonke Gabe S. , Van Driel Willemien 
Published: June 2023

5509 Background: The randomized, phase 3 OVHIPEC-1 trial (NCT00426257) investigated the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. OVHIPEC-1 previously demonstrated improved recurrence-free and overall survival after 4.7 years of follow-up. Here, we report the final survival outcomes after ten years of follow-up. In addition, we report new data on the subsequent anti-cancer treatments given after disease progression. Methods: Patients were randomized to receive interval cytoreductive surgery with or without HIPEC, after receiving three cycles of neo-adjuvant carboplatin and paclitaxel. Randomization was performed at the time of surgery when either complete (no visible disease) or optimal cytoreduction (residual tumor measuring <10mm in diameter) was anticipated. All patients received an additional three cycles of adjuvant systemic chemotherapy. We analyzed survival according to the intention-to-treat principle using stratified log-rank tests and Kaplan-Meier methods. Subsequent lines of therapy were compared between arms. Results: At a median follow-up of 10.1 years, 114 of 123 patients (92.7%) who underwent surgery alone and 109 of 122 patients (89.3%) who had surgery-plus-HIPEC experienced recurrence, progression, or death from any cause. Median recurrence-free survival was 10.7 months in the surgery group compared to 14.3 months in the surgery-plus-HIPEC group (HR, 0.63; 95% confidence interval [CI], 0.48-0.83; stratified P<0.001). One hundred and eight patients (87.8%) in the surgery group have died as compared to 100 patients (82.0%) in the surgery-plus-HIPEC group. Median overall survival was 33.3 versus 44.9 months (HR, 0.70; 95% CI, 0.53-0.92; stratified P=0.011), respectively. Subsequent anti-cancer therapies, including chemotherapy (platinum and non-platinum based), secondary surgery, poly (ADP-ribose) polymerase (PARP) inhibitors and bevacizumab, were received by 104 patients (84.6%) in the surgery group and 100 patients (82.0%) in the surgery-plus-HIPEC group. The median number of subsequent systemic treatment lines was 2 (IQR 1-3) in both arms. Conclusions: This study provides the first long-term survival analysis of HIPEC in ovarian cancer and confirms the benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. No imbalance in subsequent therapy after disease recurrence was found that could explain the improved overall survival after HIPEC. Clinical trial information: NCT00426257 .
A phase II basket trial of dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART) SWOG S1609: The vulvar cancers.
Authors: Chae Young Kwang , Othus Megan , Patel Sandip Pravin , Edwards Robert P. , Scalici Jennifer Michelle , Chung Liam Il-Young , McLeod Christine , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles David , Kurzrock Razelle 
Published: June 2023

5517 Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have proven to be effective in several malignancies but their potential role in various rare solid cancers is yet to be established. The efficacy of immunotherapy in vulvar cancer patients has not been explored. This study presents the first results of ipilimumab and nivolumab in vulvar cancers (cohort 35) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint was objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)); progression-free survival (PFS), overall survival (OS), stable disease (SD) > 6 months, and toxicity are secondary endpoints. Results: Sixteen evaluable patients (median age, 55.5 years) were analyzed. 14 cases were of squamous cell carcinoma histology and 2 were of poorly differentiated carcinoma. ORR was 18.8% (3/16, 25% when including one unconfirmed PR). There was 1 CR (SCC; PFS of 465 days) and 2 PR (both SCC; one with 57% regression with PFS of 1022 days, another with 53% regression with PFS of 501 days). Of note, there was one SCC patient with unconfirmed PR that showed 69% regression with PFS of 209 days. Overall clinical benefit rate (CBR; no progression > 6months) was 31.3% (5/16). The median PFS was 2.2 months, 6-month PFS 33%, 1-year PFS 20%. The median OS was 7.6 months, 6-month OS 62%, 1-year OS 44%. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n = 4 each). Grade 3-4 adverse events occurred in 25% of patients (n = 4). There was 1 grade 3-4 adverse event (6.7%) that led to discontinuation, and 1 (6.7%) grade 5 death adverse event. Conclusions: Ipilimumab plus nivolumab in vulvar cancers resulted in an ORR of 18.8% and CBR of 31.3%, with durable responses seen. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies exploring the role of immunotherapy in vulvar cancers are warranted. Clinical trial information: NCT02834013 .
Neoadjuvant camrelizumab plus chemotherapy for locally advanced cervical cancer (NACI study): A prospective, single-arm, phase II trial.
Authors: Chen Jing , Li Kezhen , Hu Yingjie , Han Yingyan , Shen Yuanming , Wang Yanzhou , Song Kun , Xia Bairong , Chen Xiaojun , Zou Dongling , Wang Yingmei , Sun Chaoyang , Chen Gang , Ma Ding 
Published: June 2023

5520 Background: First-line treatments for locally advanced cervical cancer (LACC) have limited efficacy and neoadjuvant chemotherapy (NACT) is an emerging approach, however, two-thirds of patients (pts) respond to it and pts without response benefit little. PD-1 inhibitors have shown promising role in recurrent or metastatic cervical cancer. This study aims to evaluate the efficacy and safety of preoperative PD-1 inhibitor camrelizumab combined neoadjuvant therapy for LACC. Methods: The study is designed as a multicenter, open-label, single-arm, prospective phase II study. Pts are enrolled if they had previously untreated LACC (2018 FIGO staged IB3, IIA2 and IIB/IIIC1r (tumor size > 4cm). Eligible pts will receive neoadjuvant chemo-immunotherapy (NACIT), defined as one cycle of cisplatin (75-80 mg/m2, iv) plus nab-paclitaxel (260 mg/m2, iv) NACT and subsequent two cycles of camrelizumab (200mg, iv) combined NACT. Either surgery or concurrent chemoradiotherapy are conducted according to the response as per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. The primary endpoint was objective response rate (ORR), and the secondary endpoints were pathological complete remission (pCR) rate, rate of postoperative adjuvant treatment, event-free survival, overall survival and safety. Results: From Dec 1, 2020 to Feb 1, 2023, 83 pts were enrolled, and 78 pts were evaluated for response. The ORR was 100% (95%CI, 95.38 to 100), with 14 (17.95%) complete response (CR) and 64 (82.05%) partial response. Regarding the pathological findings of 76 pts who underwent radical surgery, 30 (39.47% (95%CI, 28.44 to 51.35)) pts achieved pCR, while 17 (22.37%) needed postoperative adjuvant treatment as indicated in NCCN guideline, of who 14 had positive pelvic nodes, positive surgical margin, and/or positive parametrium and the other three met Sedlis criteria. RECIST CR was significantly associated with pCR ( P = 0.016). Pre-treatment PD-L1 expression (Combined Positive Score) was a predictive biomarker for RECIST CR ( P = 0.036) but not for pCR ( P = 0.078) in these evaluated patients. Grade 3 or 4 treatment-related adverse events occurred in 35 (44.87%) pts during NACIT; the most common were lymphocytopia (25.64%), neutropenia (12.82%) and leucopenia (8.97%). Conclusions: NACIT for LACC demonstrated extremely high ORR and pCR rate with manageable toxicity profile, and greatly reduced the need of postoperative adjuvant therapy. Clinical trial information: NCT04516616 .
The Normal Risk Ovarian Screening Study (NROSS): Twenty-one year update.
Authors: Han Chae Young , Lu Karen H. , Bedi Deepak , Bedia Enrique , Bevers Therese Bartholomew , Holman Laura L. , Leeds Leroy , Mathews Cara Amanda , McCann Georgia Anne-Lee , Moore Richard G. , Schlumbrecht Matthew , Slomovitz Brian , Tobias Daniel , Williams-Brown Marian Yvette , Liu Jinsong , Handy Beverly Carol , Lu Zhen , Bedia Jacob , Skates Steven J , Bast Robert C. ,   NROSS
Published: June 2023

5522 Background: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in post-menopausal women at conventional hereditary risk where significantly rising CA125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. Methods: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 women-years in a single arm study ( NCT00539162 ). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was normal ( < 1:2000), women returned in a year. If risk was elevated ( > 1:500), TVS was undertaken immediately and if risk was intermediate, CA125 was repeated in 3 months, risk recalculated, and the participant re-triaged. An average of 2% of participants were referred to TVS annually. Results: Thirty-four patients were referred for operations detecting 15 ovarian cancers and 2 borderline tumors with 12 in early stage (I-II). In addition, 7 endometrial cancers were detected with 6 in early stage. Thus, the positive predictive value (PPV) of the NROSS trial was 50% (17/34) for detecting ovarian cancer and 74% (25/34) for any cancer, far exceeding the minimum acceptable study endpoint of 10% PPV. As 4 ovarian cancers and 2 borderline tumors were diagnosed within a year of each participant’s last normal risk, the sensitivity for detecting ovarian and borderline cancer was 74% (17/23) and 70% of ROCA-detected cases (12/17) were in stage I-II. NROSS screening reduced incidence of late stage (III-IV) disease by 34% compared to the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) control arm and by 30% compared to US SEER values. Results of our NROSS trial contrast dramatically with those of the recently reported UKCTOCS that showed only a modest 14% early-stage shift, underlying a lack of reduction in mortality. Across multiple randomized trials of mammography, those trials that demonstrated at least a 20% late-stage incidence reduction had a significant mortality reduction, whereas those with less of a stage shift did not. Conclusions: An elevated ROCA, characterized by a significantly rising CA125, prompted referral of 2% of participants to TVS each year and required only 2 operations to detect each case of ovarian cancer, indicating that CA125 used in this way is adequately specific for effective screening. While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV and marked stage shift support further development of this strategy. Clinical trial information: NCT00539162 .
Active bone marrow-sparing to reduce the incidence of grade 3+ acute hematologic toxicity in patients with locally advanced cervical cancer who receive chemoradiotherapy: A single-center prospective randomized controlled trial.
Authors: Wang ShanBing , Liu JiaPei , Lei Kaijian 
Published: June 2023

5524 Background: Acute haematologic toxicity is the most common side effect of chemoradiotherapy in patients with locally advanced cervical cancer .We aim to test the efficacy of single-photon emission computed tomography-defined active bone marrow-sparing volumetric-modulated arc therapy in reducing grade 3+ acute hematologic toxicity (HT) in locally advanced cervical cancer patients treated with chemoradiotherapy. Methods: This was a prospective, single-center, open label, randomized clinical trial that enrolled locally advanced cervical cancer patients. Participants were randomized to the 99mTc sulfur colloid SPECT-defined ABMS VMAT (ABMS group) or control group, who received weekly cisplatin concurrently with volumetric-modulated arc therapy followed by high-dose-rate intracavitary brachytherapy. The ABMS group additionally received SPECT-defined ABM dose constraints. The primary endpoint was the incidence of grade 3+ acute hematologic toxicity.Secondary objectives included acute gastrointestinal toxicity, planning Target Volume (PTV) coverage, dosimetric parameters of organs at risk (OARs), progression-free survival (PFS), overall survival (OS). Results: A total of 192 FIGO stage IB-IIIB patients were randomized treated (96 each in the ABMS control groups). The median follow-up was 24.0 months. The incidence of grade 3+ acute hematologic toxicity in the ABMS group was significantly lower than that in the control group (32.3% vs 53.1%, p<0.01). The number of patients completing five cycles of cisplatin was 88.5% in the ABMS group and 75% in the control group, and the difference was significant (p=0.02). There were no significant differences in the mean dose to 95%, 97% and 99%of the PTV between the ABMS group (45.1 Gy, 44.6 Gy, and 43.3 Gy, respectively) and the control group (45.4 Gy, 44.8 Gy, and 43.6 Gy). There were no differences in dosimetric parameters of OARs ,acute gastrointestinal toxicity, 2-year PFS or 2-year OS between the two groups. Patients in the control group had nonsignificantly worse 2-year distant metastasis than patients in the ABMS group (17.8% vs. 11.1%, p=0.19). Conclusions: ABMS VMAT significantly reduced grade 3+ acute HT and improved chemotherapy delivery compared with the control treatment. We found weak evidence of the effect of ABMS VMAT on distant metastasis. Clinical trial information: ChiCTR-IOR-16010214 .