bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anlotinib combined with carboplatin/paclitaxel and maintenance anlotinib as front-line treatment for newly diagnosed advanced ovarian cancer: A phase II, single-arm, multicenter study (ALTER-GO-010).
Authors: Jiang Yi , Gao Yingchun , Zhou Huaijun , Cai Yulang , Yu Jinjin , Chen Youguo , Xue Jinling , Cheng Wenjun 
Published: June 2023

5575 Background: Several studies have shown that antiangiogenic drug combined with chemotherapy as first-line treatment, followed by antiangiogenic drug maintenance therapy significantly improve outcomes for patients with ovarian cancer. Anlotinib, a highly effective VEGFRs, FGFRs, PDGFRs and c-kit multi-target tyrosine kinase inhibitor, has been approved for multiple tumor types in China. The aim of this single arm, multicentric, phase II study is to investigate the efficacy and safety of using anlotinib combined with carboplatin/paclitaxel as front-line treatment for advanced ovarian cancer patients. Methods: Eligible patients with FIGO stage III–IV primary epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and ECOG PS 0-1 undergo primary cytoreductive surgery or interval debulking surgery, will receive 6-8 cycles of chemotherapy (paclitaxel 175 mg/m2 + carboplatin area under the curve [AUC] 5 q3w) and anlotinib (12 mg po qd, days 1-14, 21 days per cycle, anlotinib will be omitted from the first treatment cycle to prevent delayed wound healing). After chemotherapy finished, anlotinib continues as maintenance monotherapy until disease progression, unacceptable toxicity, or death. Patients with prior anti-angiogenic therapy or major surgical procedure within 28 days before starting anlotinib therapy will be excluded. The primary endpoint is progression free survival (PFS). Key secondary endpoints include overall response rate, disease control rate per RECIST1.1, overall survival, safety. Results: From 9 Sep 2021 to 30 Jan 2023, 30 pts were enrolled, including 96.7% (29/30) high-grade serous carcinoma (HGSC) and 3.33% (1/30) endometrioid carcinoma (EC). The median age was 56 years old, with 96.7% (29/30) patients in FIGO stage III and 3.33% (1/30) in stage IV Median follow-up was 5.36 (95% CI: 3.68, - 7.98) months. PFS rates at 6 months and 9 months were both 100%. Twenty-nine patients (96.7%) experienced adverse events (AE) of any level. The most common AEs include white blood cell decreased, neutrophil count decreased, anemia, platelet count decreased, lymphocyte count decreased and hypertension. There was no treatment-related death during the study. Conclusions: Preliminary results of anlotinib combined with carboplatin/paclitaxel have shown favorable efficacy and tolerated safety profile in newly diagnosed advanced ovarian cancer patients. Clinical trial information: NCT04807166 .
Understanding differences in the rates of BRCA/HRD testing and treatment in 1st line maintenance in patients with ovarian cancer treated by gynecologic oncologists compared to other providers: A quality initiative by Integra Connect (IC) PrecisionQ.
Authors: Kudrik Fred J. , Gart Mike , Blanc Simon , English Sandy , Alwon Erin 
Published: June 2023

5576 Background: The role of PARPi in the treatment of advanced ovarian cancer (aOC) has expanded in recent years. In this context, South Carolina Oncology Associates (SCOA) partnered with Integra Connect (IC) on a quality initiative (QI) to evaluate the rate of BRCA and HRD testing in newly diagnosed OC patients and the use of maintenance therapy in the 1st line (1L) setting in aOC. Patients with aOC at SCOA are typically managed by gynecologic oncologists. Methods: Using the IC Precision Q real-world database of over 1 million cancer patients across 275 sites of care, we assessed newly diagnosed OC patients evaluated via medical chart curation from 1/1/2020 to 6/30/2022 for BRCA and HRD testing at SCOA (N = 81) and other oncology practices (N = 1,045). We also studied the use of maintenance therapy in patients with stage II-IV OC who completed platinum-based chemotherapy from 1/1/2020 to 6/30/2022 at SCOA (N = 75) and other oncology practices (N =899). SCOA was compared to other oncology practices in terms of provider specialty treating the patient, rates of HRD and BRCA testing, and use of 1L maintenance treatment in patients with or without BRCA or HRD mutations. Descriptive analyses were used. Proportions were compared using a two tailed two sample z-test. Results: Among newly diagnosed patients at SCOA, 95% of patients with OC were primarily managed by a gynecologic oncologist compared to 5% at other practices. The rate of BRCA testing at SCOA was 81% (66 of 81) compared to 75% (788 of 1045) and HRD testing was 60% (49 of 81) compared to 39% (403 of 1045) at other oncology practices in the IC database. The difference in HRD testing was significant (p < 0.01). The use of 1L maintenance regardless of biomarker status was 64% (48 of 75) at SCOA compared to 50% (449 of 899) at other practices. The difference in 1L maintenance use was significant (p<0.05). PARPi were used at SCOA for maintenance therapy in 82% (38 of 46) of patients compared to 74% (314 of 427) at other practices. The use of maintenance in BRCA or HRD positive patients was 84% (21 of 25) at SCOA compared to 75% (151 of 201) for other practices. Conclusions: In this real-world study, treatment by gynecologic oncologists was associated with higher rates of BRCA and HRD testing and higher use of 1L maintenance treatment in patients with aOC compared to other practices. These findings underscore the importance of gynecologic oncologists in the management of aOC to ensure optimal testing and adherence to treatment guidelines.
Decision value of the circulating tumor DNA on the adjuvant anti-Her2 regimens in patients with Her2-positive breast cancer treated with neoadjuvant therapy.
Authors: Lin Po-Han , Tsai Li-Wei , Lo Chiao , Kuo Sung-Hsin , Huang Chiun-Sheng 
Published: June 2023

558 Background: A significant proportion of patients with early-stage Her2-positive breast cancer are treated with neoadjuvant therapy (NAT). Previous studies suggested the presence of circulating tumor DNA (ctDNA(+)) after NAT was a significant predictor for recurrence in early-stage Her2-positive breast cancer. However, it is unknown whether the ctDNA(+) was able to guide adjuvant anti-Her2 regimen for patients with early-stage Her2-positive breast cancer? Methods: We enrolled 117 patients who had Her2-positive breast cancer and received NAT. CtDNA was collected before and after NAT as well as detected by Oncomine breast cell-free DNA assay. Adjuvant anti-Her2 regimens were classified as T-DM1 and non-T-DM1. Recurrence-free survival (RFS) was estimated by Kaplan-Meier method and hazard ratio (HR) with 95% confidence interval (CI) was analyzed by Cox proportional hazards regression model. Results: Of the 117 patients enrolled, there were 18 patients receiving adjuvant T-DM1 and 99 receiving trastuzumab (N = 70) or trastuzumab plus pertuzumab (N = 29). CtDNA(+) was observed in 79 patients before NAT while 32 patients remained ctDNA(+) after NAT. Multivariate Cox regression model showed that ctDNA(+) after NAT (HR 3.497 95% CI 1.364-8.964, p = 0.009) was an independently poor factor that predicted recurrence, after adjustment with clinical and pathologic parameters. Non-pCR was associated with an inferior trend of survival but not a statistically significant factor of recurrence. Patients who received adjuvant T-DM1 had a reduced risk of recurrence (HR 0.118, 95% CI 0.015-0.931, p = 0.043) in the multivariate analysis. Further analysis of the prognostic value of adjuvant T-DM1 therapy in context with and without ctDNA, we divided patients into 4 subgroups: ctDNA(-)/non-T-DM1, ctDNA(-)/T-DM1, ctDNA(+)/non-T-DM1 and ctDNA(+)/T-DM1. Our data revealed that patients with ctDNA(+)/T-DM1 had a significantly better RFS than those with ctDNA(+)/non-T-DM1 (p = 0.019). The 5-year RFS was similar between patients with ctDNA (+)/T-DM1 and those with ctDNA(-) after NAT. Conclusions: The presence of ctDNA in patients with early-stage Her2-positive breast cancer after NAT was independently associated with disease recurrence; however, ctDNA(+) after NAT became inconsiderable when patients were treated with adjuvant T-DM1 therapy, which represented ctDNA(+) as an important factor determining adjuvant anti-Her2 regimen.
Triplet maintenance (olaparib, pembrolizumab, and bevacizumab) in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer: A multi-center, single-arm phase II study (OPEB-01).
Authors: Kim Yoo Na , Park Boram , Joung Je-Gun , Kim Jae-Weon , Kim Byoung-Gie , Kim Sang Wun , Kim Hee Seung , Choi Chel Hun , Lim Myong Cheol , Ngoi Natalie Yl , Tan David Shao Peng , Lee Jung-Yun 
Published: June 2023

5584 Background: The optimal treatment of BRCA 1/2 non-mutated patients with platinum-sensitive recurrent ovarian cancer remains unknown. In this study, we evaluated the efficacy and safety of triplet maintenance therapy in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer. Methods: BRCA 1/2 non-mutated patients with platinum-sensitive recurrent epithelial ovarian cancer, showing a complete/partial response after second-line platinum-based chemotherapy, were eligible. Triplet maintenance therapy (olaparib, bevacizumab, and pembrolizumab) was administered until disease progression or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS) rate at six months after therapy initiation. The secondary endpoints were PFS, overall survival, and safety. The translational objectives included biomarker evaluation with respect to survival outcomes. Results: Forty-four patients were enrolled (median age 61 years), majority with high-grade serous carcinoma (93.2%) and partial response (75.0%) to second-line chemotherapy. Overall, 54.6% were homologous recombination deficiency (HRD)-positive (genomic instability score ≥ 42) and 63.6% had PD-L1 positive tumors (combined positive score [CPS] ≥ 1). At 6 months, the PFS rate was 88.6% (95% confidence interval [CI] 75.4–96.2). The median PFS has not been reached. The most common ≥ grade 3 treatment-related adverse events (AEs) were anemia (20.5%) and neutropenia (6.8%), but there were no grade 4 AEs. Exploratory analysis demonstrated remarkable survival outcomes regardless of HRD status, whereas patients with PD-L1 CPS ≥ 1 showed improved PFS compared to those with PD-L1 CPS < 1 ( P = 0·032). Analysis of molecular consensus subtype of the pre-treatment tissue samples showed that patients with mesenchymal subtype demonstrated poor PFS, compared to non-mesenchymal subtypes (p = 0.0023). Conclusions: This is the first report on triplet maintenance therapy in BRCA non-mutated platinum-sensitive recurrent ovarian cancer. The results show that the triplet maintenance therapy is efficacious with manageable toxicity, showing a particular promise for patients with molecular consensus subtype other than mesenchymal. Clinical trial information: NCT04361370 .
Immune features of ovarian tumors with a good response to neo-adjuvant chemotherapy in combination with an anti-PD-L1 alone or with an anti-CTLA4: Data from the randomized IneOV trial (a GINECO study).
Authors: Leary Alexandra , Chardin Laure , Genestie Catherine , Lortholary Alain , Alexandre Jerome , De La Motte Rouge Thibault , D'hondt Veronique , Floquet Anne , Savoye Aude-Marie , Delanoy Nicolas , Gavoille Céline , You Benoit , Grenier Julien , Yaniz-Galende Elisa 
Published: June 2023

5586 Background: We have shown that chemotherapy may have immunomodulatory properties and prime the tumor microenvironment (TME) by recruiting cytotoxic immune cells. We previously reported that neoadjuvant chemotherapy (NACT) associated with Durvalumab (D) +/- Tremelimumab (T) resulted in encouraging complete resection (70%) and complete pathological response (18%) rates in patients with unresectable ovarian cancer. Here, we aimed to 1) characterize the immune TME at baseline of responders compared to non-responders and 2) describe changes in immune TME in paired tumor samples at diagnosis and after 3 cycles of NACT with D +/- T in the randomized IneOV trial. Methods: Tumor samples from IneOV trial (55 at diagnosis, 40 after treatment) were analyzed for CD3+, CD68+ and CD20+ by multiplexed immunohistochemistry. Stromal and intra-epithelial TILs were scored as percentage of positive surface. Patients were classified as good pathological responders (pR) (CRS3) or pathological non-responders (pNR) (CRS1 or 2). Intra-tumoral T cell infiltration was described as High or Low (intraepithelial (ie)CD3+ > median vs < , respectively). Non parametric statistical tests were used. We evaluated the correlation of the markers with each others (Spearman test) and with pathological response rate (Mann-Withney test). Results: At diagnosis, in the intra-epithelial compartment of the TME, the most abundant cells were macrophages (median ieCD68+ = 3,4) compared to T (ieCD3+ = 1.1), B (ieCD20+ ND) ANOVA p-value = 0.002 and < 0.0001 respectively . In individual tumors, infiltration by the 3 different immune subsets was poorly correlated suggesting immune TME heterogeneity in OC. Pathological response was evaluable in 64 patients: 19 pR and 45 pNR. At diagnosis, CD3+ (p = 0.02) and CD68+ (p = 0.006) infiltration was significantly higher in pR tumors compared to pNR. Most of pR (76%) had high intra-tumoral CD3+ infiltration versus 39% in pNR (p = 0.011). After treatment, tumors with pR showed significantly greater CD3+ intra-epithelial infiltration compared to pNR (p = 0.047). Conclusions: Our results suggest that good pathological response to NACT +D+/-T is associated with high levels of both T cells and macrophages in iTME at baseline, and increased intratumoral T cell infiltration post-treatment. Work is ongoing to further characterize the iTME, especially in pNR to identify other strategies to enhance the anti-tumor immune response. Clinical trial information: NCT03249142 .
Blinded-assessment of a solution to evaluate olaparib maintenance treatment efficacy in patients with ovarian cancer from the GINECO/ENGOT PAOLA-1 trial.
Authors: Buisson Adrien , Saintigny Pierre , Constantoulakis Pantelis , Oikonomaki Katerina , Samara Stavroula , Harter Philipp , Pignata Sandro , Gonzalez Martin Antonio , Schauer Christian , Fujiwara Keiichi , Vergote Ignace , Colombo Nicoletta , Pujade-Lauraine Eric , Treilleux Isabelle , Ray-Coquard Isabelle Laure 
Published: June 2023

5588 Background: SOPHiA DDM Dx HRD Solution (SOPHiA GENETICS, SA) combines analysis of genomic instability with mutational status of HRR genes, including BRCA1/2, generated through a single genomic workflow in order to to predict Homologous Recombination Deficiency (HRD) status in ovarian cancer (OvCa) samples. Previous evaluation of SOPHiA DDM Dx HRD Solution demonstrated its results to be highly concordant with a reference HRD method. As part of the ENGOT HRD initiative, we present updated clinical relevance results of SOPHiA DDM Dx HRD Solution. Methods: GINECO/ENGOT-Ov25 PAOLA-1 trial randomized (2:1) 804 patients (pts) to receive after the end of first-line platinum-based chemotherapy either maintenance olaparib+bevacizumab or placebo+bevacizumab for up to 2 years. DNA from a sub-cohort of 384 formalin-fixed paraffin-embedded (FFPE) OvCa pts samples included in the PAOLA-1 clinical trial were analyzed using SOPHiA DDM Dx HRD Solution(*). We combined SOPHiA DDM Dx HRD Solution genomic instability score, with BRCA mutational status obtained from a Clinical Decision Support module, and clinical interpretation of Variants of Unknown Significance to establish the pts HRD status and investigated differences in progression-free survival (PFS) in the olaparib+bevacizumab and placebo+bevacizumab arms between pts with HRD positive or HRD negative test. Results: We determined the HRD status of 98.4% of pts using SOPHiA DDM Dx HRD Solution. The median PFS time for pts with HRD positive tumors was 35.7 months longer in the olaparib+bevacizumab arm than in the placebo+bevacizumab arm (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.25-0.51, p< 0.001), confirming the findings of our previous interim analysis. No significant difference in PFS was observed between treatment arms in pts with HRD negative test (HR, 1.02; 95% CI, 0.71-1.48; p= 0.90). Conclusions: These clinical relevance results from the SOPHiA DDM Dx HRD Solution evaluation on the PAOLA-1 samples further support the value of combining low-pass whole genome and targeted sequencing in a unique workflow for reliable and cost-effective HRD testing and future patient stratification. (*) Comparison data generated using the CE-IVD pipeline with Clinical Decision Support module for BRCA status only available in EU, Switzerland, UK.
The role of Chemotherapy Response Score (CRS) in the decision making process for patients with advanced high grade serous ovarian cancer undergoing neoadjuvant chemotherapy.
Authors: Marchetti Claudia , Ergasti Raffaella , Capomacchia Filippo Maria , Giannarelli Diana , Sassu Carolina Maria , Zannoni Gian Franco , Scambia Giovanni , Fagotti Anna 
Published: June 2023

5591 Background: The role of chemotherapy response score (CRS) in predicting PARP inhibitors (PARPi) response for high grade serous Advanced Ovarian Cancer (AOC) patients undergoing Neoadjuvant Chemotherapy (NACT) has never been investigated. Also, the correlation between CRS and Homologous Recombination status (HRs) is unclear. Methods: In this observational retrospective study, we collected data from patients with high grade serous AOC, FIGO stage III-IV, undergoing NACT and subsequent Interval Debulking Surgery (IDS) from 2017 to 2021. KELIM score, CRS and BRCA status were considered; additionally, HRs (Foundation test) was reported when available. Primary endpoint was Progression Free Survival (PFS) according to CRS (CRS 1/2 vs 3) in patients receiving PARPi. Results: We enrolled 309 patients; 102 had CRS3 and 193 had CRS1/2 (14 were undetermined). Patients with CRS3 and PARPi maintenance showed the best prognosis, compared to all other subgroups (median PFS Not Reached, p=0.014); additionally, in the BRCA wild type population, CRS3 was predictive of longer survival (median PFS for the CRS3+PARPi BRCAwt population 24 months compared with 15 months for the CRS1/2+PARPi BRCAwt patients, p=0.041). Furthermore, among the 44 patients with known HRs, 59.1% of HR Deficiency (HRD) positive patients had CRS3, conversely 22.7% of HRD negative ones had a CRS3 ( p=0.048) Finally, we found out that a favorable KELIM was significantly associated with CRS3 in the all-comers patients ( p=0.007) and in the BRCAwt ( p=0.04), but it was not predictive of PARPi response. Conclusions: Our findings suggested that the higher the CRS at the interval cytoreduction, the better the subsequent PARPi response. CRS correlates with PARPi response, as the HRD test does in other clinical trials and it may be considered as a surrogate of HRD status. We have planned to retrospectively perform HR test on a total sample size of 77 patients who received PARPi to corroborate this hypothesis. [Table: see text]
Real-world overall survival in second-line maintenance niraparib monotherapy vs active surveillance in BRCA wild-type patients with recurrent ovarian cancer.
Authors: Coleman Robert L. , Perhanidis Jessica , Kalilani Linda , Zimmerman Nicole M. , Golembesky Amanda , Moore Kathleen N. 
Published: June 2023

5592 Background: The Phase 3NOVA trial assessed niraparib versus placebo as a maintenance treatment (tx) for patients (pts) with recurrent ovarian cancer (OC) who were platinum-sensitive after ≥2 regimens; progression-free survival was the primary endpoint and overall survival (OS) was a secondary endpoint (NCT01847274). The aim of this real-world study was to compare OS in a breast cancer gene wild-type ( BRCAwt) population of pts with recurrent OC and who received second-line maintenance (2Lm) niraparib monotherapy or were under active surveillance (AS). Methods: This study used the US nationwide Flatiron Health de-identified electronic health record (EHR)-derived database. Pts diagnosed with epithelial OC between 1Jan2011–31May2021 who completed 2L therapy between 1Jan2017–2Mar2022 were eligible for inclusion. Pts were BRCAwt, had an ECOG PS score 0–1, epithelial histology, and platinum-sensitive disease with ≥6 months between end of first-line tx and start of 2L tx. Pts were assigned to 2Lm niraparib or AS cohorts based on their management following 2L non-maintenance therapy (≤120 days). Follow-up was measured from the index date (end of 2L non-maintenance therapy) until end of study (31May2022), last activity, or death, whichever came first. A target trial emulation cloned inverse probability of censoring weighting (IPCW) methodology was selected a priori to minimize bias. IPCW median OS and hazard ratios (HR) for 2Lm versus AS were estimated with Kaplan-Meier curves and Cox regression models. Results: Overall, 266 BRCAwt pts were included and received niraparib 2Lm (N=123) or were under AS (N=143). Across 2Lm and AS cohorts, prior to cloning and IPCW, 23.6% and 34.3% of pts were aged ≥75 years, and 26.0% and 16.8% had an EHR value for race as other than White, respectively. The majority of pts were from community practice (80.5% and 90.2%, respectively), had serous OC (79.7% and 81.1%) and had Stage III disease (53.7% and 60.8%). Homologous recombination deficiency status was unknown for 92.7% and 86.0% of pts in 2Lm and AS cohorts, respectively. Median follow-up for 2Lm and AS cohorts was 16.8 (Quartile [Q] 1, Q3: 10.4, 28.7) and 10.2 (Q1, Q3: 4.1, 23.7) months, respectively. IPCW median OS was 28.1 (95% confidence interval [CI]: 22.5, 43.2) and 21.5 (95% CI: 14.7, 27.0) months (HR: 0.63 [95% CI: 0.45, 0.88]) for niraparib 2Lm and AS cohorts, respectively and survival rates at 24 months were 58.2% (95% CI: 47.5, 67.6) and 46.1% (95% CI: 33.6, 57.7). Conclusions: This analysis provides real-world data on OS among pts with OC receiving niraparib 2Lm or under AS in the 2L setting following chemotherapy. Funding: GSK study (219306). Editorial support was provided by Fishawack Health, funded by GSK.