bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of advances in epithelial ovarian cancer treatment on population mortality.
Authors: Wang Aifen , Ye Qing , Lv Jinghuan , Hu Weidong , Feng Ninghan , Hou Shunyu 
Published: June 2022

5540 Background: Epithelial ovarian carcinoma is the most common and progressive subtype of ovarian cancer. Mortality trends based on race remains unclear. Methods: SEER was used to assess epithelial ovarian cancer mortality and relevant deaths from epithelial ovarian cancer to incident cases. Population-level mortality trends were evaluated according to specific causes. In addition, epithelial ovarian cancer incidence and survival was assessed according to calendar year and race. We applied Joinpoint software to evaluate trends in incidence or incidence-based mortality. Results: Age-adjusted incidence of white patients was the highest, followed by Asians and Black patients. Incidence-based mortality of Asian patients was the lowest among all patients, followed by White and Black patients. Incidence-based mortality of all causes of death of epithelial ovarian cancer increased sharply by 65.09% annually from 2000 through 2002, then rose gradually by 9.45% annually from 2002 through 2005, and then increased more slowly annually from 2005 through 2018. Other causes of death of incidence-based mortality displayed similar trends. However, incidence-based mortality of specific ovarian epithelial cancer deaths displayed an annual decrease of 0.08% from 2005 through 2018, following a sharp annual increase of 65.68% from 2000 through 2002 and 6.55% from 2002 through 2005. White patients with epithelial ovarian cancer showed the highest 2-year relative survival, followed by Asians, Black patients and Native Americans, with all patients showing an improved survival rate. Among White patients with epithelial ovarian cancer, incidence increased annually by 1.98% from 2000 through 2011 and then flattened out to an annual increase of 0.03%. Incidence-based mortality of White patients increased sharply by 56.70% annually from 2000 through 2002, then increased slowly by 7.90% annually from 2002 through 2005, and 2.00% annually from 2005 through 2018. Among Asian patients with epithelial ovarian cancer, incidence increased at an annual rate of 2.39% from 2000 through 2018. Incidence-based mortality of Asian patients increased steeply by 78.70% annually from 2000 through 2002, then slowed down to an annual rate of 2.50% from 2002 through 2018. Among Black patients with epithelial ovarian cancer, incidence increased annually by 10.83% from 2000 through 2002 and 2.43% from 2006 through 2016 and declined annually by 0.82% from 2002 through 2006 and by 1.82% from 2016 through 2018. Incidence-based mortality of Black patients displayed a sharp annual increase of 63.70% from 2000 through 2002, then slowed to an annual rate of 1.90% from 2002 through 2018. Conclusions: Incidence-based mortality of specific ovarian epithelial cancer death decreased annually from 2005 through 2018. These results may be related to treatment advances of epithelial ovarian carcinoma, particularly surgical strategy and chemotherapy.
Efficacy of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer in phase 3 PRIME study: A subgroup analysis by response to first-line platinum-based chemotherapy.
Authors: Yin Rutie , Li Ning , Wu Lingying , Wang Jing , Zhu Jianqing , Pan Lingya , Kong Beihua , Zheng Hong , Liu Jihong , Wu Xiaohua , Wang Li , Huang Yi , Wang Ke , Zou Dongling , Zhao Hongqin , Wang Chunyan , Lu Weiguo , Zhen Xiaoa , Hang Wenzhao , Hou Jianmei 
Published: June 2022

5551 Background: In PRIME (NCT03709316), niraparib significantly reduced the risk of disease progression or death versus placebo (PBO) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34–0.60) in Chinese patients (pts) with newly diagnosed, advanced ovarian cancer (OC), regardless of biomarker status. As response to chemotherapy is deemed to be associated with prognosis in OC, this subgroup analysis of the PRIME study aims to better understand niraparib treatment effect in pts based on response to first-line platinum-based chemotherapy (1L CT). Methods: This randomized, double-blind, PBO-controlled, phase 3 trial enrolled adults with newly diagnosed, stage III or IV OC who achieved a complete response (CR) or partial response (PR) to 1L CT and received primary or interval cytoreductive surgery, irrespective of residual disease status after surgery. Pts were randomized (2:1) to receive niraparib or PBO, whose starting doses were individualized based on baseline bodyweight and platelet count, with stratification according to status of germline BRCA mutations (yes or no), tumor homologous recombination status (deficient or proficient), receipt of neoadjuvant chemotherapy (yes or no), and clinical response to 1L CT (CR or PR). This prespecified exploratory analysis reports progression-free survival (PFS) and HRs based on clinical response to 1L CT. The data cut-off date was 30 September 2021. Results: Of the 384 pts randomized, 315 (82.0%) and 69 (18.0%) had a CR (212 niraparib, 103 PBO) or PR (43 niraparib, 26 PBO) to 1L CT, respectively. Baseline characteristics are presented in the Table. The overall PFS median follow-up was 27.5 months. Niraparib significantly extended PFS compared with PBO: the median PFS was 29.4 months for niraparib versus 8.3 months for PBO (HR=0.45; 95% CI, 0.32–0.61; P<0.001) in the CR group and was 19.3 months for niraparib versus 8.3 months for PBO (HR=0.45; 95% CI, 0.23–0.86; P=0.014) in the PR group. Conclusions: In pts with newly diagnosed advanced OC, PFS was substantially prolonged with niraparib versus PBO, regardless of response to chemotherapy and biomarker status. Moreover, pts who achieved a CR appeared to receive larger PFS benefit from niraparib than those with a PR. Clinical trial information: NCT03709316. [Table: see text]
Real-world outcomes associated with bevacizumab combined with chemotherapy in platinum-resistant ovarian cancer.
Authors: Moffat Gordon Taylor , Kong Weidong , Booth Christopher M. , Ethier Josee-Lyne 
Published: June 2022

5555 Background: In the pivotal Aurelia study, addition of bevacizumab (bev) to physician’s choice chemotherapy (paclitaxel, liposomal doxorubicin or topotecan) for platinum-resistant (PL-R) ovarian cancer (OC) was associated with improved progression-free survival (PFS; 6.7 vs 3.4 mos; hazard ratio (HR) 0.48, p = 0.001) but not overall survival (OS; 16.6 vs 13.3 mos HR 0.85, p = 0.174); the latter finding may relate to extensive crossover. In an exploratory subgroup analysis by treatment arm, benefits were particularly marked for bev + paclitaxel where median PFS (mPFS) increased from 3.9 to 10.4 mos (HR 0.46; 95%CI 0.30-0.71) and increases in OS approached statistical significance (HR 0.65; 95%CI, 0.42-1.02; 22.4 v 13.2 mos). Here we describe utilization of bev for PL-R OC and outcomes in routine clinical practice. Methods: The Ontario Cancer Registry and the New Drug Funding Program databases were utilized to identify all patients treated with bev plus chemotherapy (paclitaxel, liposomal doxorubicin or topotecan) for PL-R OC following its approval in 2017. Time on treatment (ToT) was defined as time from first to last bev treatment; this was used as a surrogate for PFS in routine practice. Median OS (mOS) was determined using the Kaplan-Meier method. Factors associated with ToT and OS were identified using a Cox proportional hazard model. A before and after comparison analysis was performed to determine mOS for patients treated pre- (2011-2017) and post-bev (2017-2019) approval. Results: From Oct 2017 to Dec 2019, 180 patients received bev + chemotherapy for first-line PL-R OC. Mean age was 63 years old, and 80% had serous OC. Bev was most often combined with liposomal doxorubicin (64 %) followed by paclitaxel (34%) and topotecan (2%). Median ToT was 3 months and OS was 11 months. ToT and OS were longer in patients who received paclitaxel as chemotherapy backbone (5 mos [ToT]; 14 mos [OS]) than those who received bev with liposomal doxorubicin (2 mos; 9 mos) or topotecan (2 mos; 6 mos). In multivariable models, ToT was superior in patients who received bev + paclitaxel than bev + liposomal doxorubicin (HR 0.40; 95%CI 0.28-0.57; p < 0.0001), and worse with longer time from diagnosis to bev start (1.03; 1.01-1.05; p = 0.0120). OS was also significantly longer in those who received paclitaxel vs liposomal doxorubicin (HR 0.54; 95%CI 0.30-0.98; p = 0.043). In a before and after analysis, patients treated in the pre- (n = 1290) and post-bev (n = 360) era had mOS of 8 and 9 months respectively. Post mOS increased for patients receiving paclitaxel (7 vs 12 months) but not with liposomal doxorubicin (9 vs 7 months). Conclusions: ToT and OS associated with bev for PL-R OC are shorter in a real-world population compared to results reported in AURELIA. ToT and OS were longer with bev + paclitaxel than with other chemotherapy agents.
Breast cancer incidence in patients with BRCA-related advanced ovarian cancer receiving olaparib-based maintenance therapy: A pooled analysis from phase III clinical trials.
Authors: Bartoletti Michele , Montico Marcella , Mazzeo Roberta , De Scordilli Marco , Musacchio Lucia , Lucia Emilio , Giorda Giorgio , Massarut Samuele , Urbani Martina , Miolo Gianmaria , Viel Alessandra , Garutti Mattia , Da Ros Lucia , Scalone Simona , Nicoloso Milena , Corsetti Serena , Sorio Roberto , Lorusso Domenica , Pignata Sandro , Puglisi Fabio 
Published: June 2022

5566 Background: As the prognosis of BRCA-related advanced ovarian cancer (AOC) continues to improve thanks to the introduction of targeted therapies like poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab, the occurrence of second primary tumors, in particular breast cancer (BC), is assumed to be more common. Despite this, data on the incidence of BC in this population are poor and guidelines for BC screening or risk reducing strategies are lacking. Methods: Published data from recent PARPi-based, phase III clinical trials involving germline BRCA mutated AOC were reviewed and analyzed. Only studies in which the incidence of at least one second primary solid tumor was reported were included. Cases of second primary BC cancers were pooled to calculate cumulative incidence according to the median follow-up period for each trial. 95% confidence interval (CI) was considered. Results: Four trials (SOLO1, PAOLA1, SOLO2 and SOLO3) involving 1186 germline BRCA 1-2 mutated AOC patients were included ( BRCA1, n = 816; BRCA2, n = 360; BRCA1 + BRCA2, n = 4; missing, n = 6). In all trials, patients were randomized to receive olaparib +/- bevacizumab (n = 788) versus placebo or standard therapies (n = 398). Median age at diagnosis of AOC was 56 years (range, 29-87). With a follow-up ranging from 3.9 months to 5 years, 16 new cases of BC were recorded, 10 in PARPi-based arms and 6 in control arms. Only two patients had a previous history of BC. The total cumulative incidence of BC was 1.37% (95% CI, 0.77-2.18), while cumulative incidences were 1.26% (95% CI, 0.61-2.31) and 1.51% (95% CI, 0.55-3.25) in PARPi-based arms and control arms, respectively. In a sensitivity analysis excluding the SOLO3 trial with the shortest follow-up, the total cumulative incidence was 1.63% (95% CI, 0.92-2.67). Other 20 cases of second primary solid tumors were registered, including 4 cases of non-small cell lung cancer. Conclusions: Patients with germline BRCA-related AOC receiving PARPi-based maintenance therapy can be reassured about the risk of second primary BC and intensive screening should be avoided at least in early treatment phase. More data with long term follow-up are needed.
MOONSTONE/GOG-3032: Interim analysis of a phase 2 study of niraparib + dostarlimab in patients (pts) with platinum-resistant ovarian cancer (PROC).
Authors: Randall Leslie M. , O'Malley David M. , Monk Bradley J. , Coleman Robert L. , Gaillard Stephanie , Adams Sarah F. , Duska Linda R. , Cappuccini Fabio , Dalton Heather , Holloway Robert W. , Huang Marilyn , Chon Hye Sook , Cloven Noelle Gillette , ElNaggar Adam , O'Cearbhaill Roisin Eilish , Waggoner Steven E. , Wang Zebin , Zhi Eric , Samnotra Vivek , Konstantinopoulos Panagiotis A. 
Published: June 2022

5573 Background: PROC is poorly responsive to anticancer therapy. PARP inhibitors such as niraparib may increase neoantigen load and synergize with anti-PD-1 agents. TOPACIO reported a preliminary objective response rate (ORR: 18%) and disease control rate (DCR: 65%) to niraparib + pembrolizumab in pts with OC of any BRCA status. MOONSTONE sought to determine efficacy in pts without BRCA mutation ( BRCAm). Methods: In this phase 2 open-label, single-arm study, eligible pts received 1–3 prior lines of therapy including platinum, taxane, and bevacizumab, had RECIST v1.1 radiographic progression within 6 mo of last platinum line and had no known germline BRCAm. Pts were treated with niraparib 300/200 mg PO daily (based on weight/platelets) and 500 mg dostarlimab IV Q3W (cycles 1–4) followed by 1000 mg Q6W until disease progression, toxicity or consent withdrawal. Programmed death-ligand 1 (PD-L1) positive status was determined by Ventana SP263 assay using visually-estimated combined positive score ≥5%. The primary endpoint was investigator-assessed ORR per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), DCR, and safety. Futility was prespecified as ≤5 responses in the first 40 pts. Results: At interim analysis (data cutoff Oct 6, 2021), 41 pts were enrolled; median age was 65.0 y (range 35–77). At baseline, 8 (20%)/22 (54%)/11 (27%) pts had received 1/2/3 prior lines of therapy, respectively; 26 (63%) pts had primary resistance to platinum therapy and 15 (37%) were sensitive to first platinum treatment. Overall, tumors were PD-L1+/PD-L1–/unknown in 13 (32%)/25 (61%)/3 (7%), respectively. Efficacy results are shown in the Table. Treatment-related adverse events were reported in 95% of pts, most commonly nausea (56%), fatigue (34%), vomiting (32%), and anemia (29%). Conclusions: PROC remains difficult to treat; the ORR observed with niraparib + dostarlimab did not reach the threshold for 2nd-stage accrual in this cohort of pts with PROC, no known BRCAm, and prior bevacizumab treatment. PD-L1 status did not predict response; HRD testing is in process. Although DCR was 29%, futility was declared based on low ORR. The safety of the combination was similar to the safety profile of each monotherapy. Clinical trial information: NCT03955471. [Table: see text]
Integrated safety summary of single-agent mirvetuximab soravtansine in patients with folate receptor α (FRα)-positive recurrent ovarian cancer: Phase 1 and 3 clinical trials.
Authors: Moore Kathleen N. , Lorusso Domenica , Oaknin Ana , Oza Amit M. , Colombo Nicoletta , Van Gorp Toon , O'Malley David M. , Banerjee Susana N. , Murphy Conleth G. , Harter Philipp , Konecny Gottfried E. , Pautier Patricia , Method Michael W. , Wang Jiuzhou , Birrer Michael J. , Coleman Robert L. , Matulonis Ursula A. 
Published: June 2022

5574 Background: Available chemotherapies for platinum-resistant ovarian cancer (PROC) have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is a first-in-class antibody drug conjugate (ADC) comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent that has demonstrated significant anti-tumor activity in this difficult to treat population. The objective is to characterize the tolerability profile of MIRV in a pooled analysis of experience when administered as monotherapy in patients (pts) with FRα positive recurrent ovarian cancer. Methods: Retrospective pooled analysis included pts enrolled across three studies: phase 1 first-in-human, phase 3 FORWARD I, and phase 3 SORAYA. Analysis included pts with FRα positive recurrent ovarian cancer and those pts with low, medium, and high FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 25% of cells with PS2+ staining intensity). All pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. Results: 464 pts were included from 15 countries, with key characteristics: median age 63 yrs, 87% 1-3 prior therapies, 91% platinum free interval ≤6 months, 65% prior bevacizumab, and 25% prior PARPi. The most common treatment-related adverse events (TRAE) (all grade, grade 3+) included blurred vision (42%, 3%), nausea (40%, 2%), diarrhea (33%, 2%), fatigue (31%, 2%), keratopathy (26%, 3%), and dry eye (22%, 1%). TRAEs leading to a dose delay or reduction occurred in 33% and 21% of pts, respectively. Seven % discontinued due to a TRAE. Four pts ( < 1%) discontinued MIRV due to an ocular event. Ninety % of pts with a grade 2+ blurred vision resolved to grade 0 or 1, 93% of pts with grade 2+ keratopathy resolved to grade 0 or 1. No corneal ulcers or perforation have been reported and no patient with a serious ocular event has been reported to have permanent sequelae. Conclusions: In a pooled analysis of 464 patients, MIRV monotherapy has a differentiated and predictable safety profile consisting primarily of low grade and reversible gastrointestinal and ocular events. These events were managed with supportive care and dose modifications if needed, with a low rate of treatment-related discontinuation. The safety profile of MIRV in recurrent ovarian cancer along with the anti-tumor activity in PROC (32.4% ORR Matulonis SGO 2022) support a favorable benefit/risk in this population. Clinical trial information: NCT01609556, NCT04296890, NCT02631876.
Assessment of FOXC1 expression as a predictor of response to neoadjuvant taxane plus platinum regimens in primary triple-negative breast cancer: Retrospective analysis of three clinical trial cohorts.
Authors: Ray Partha , Ray Tania , Lopez-Tarruella Cobo Sara , del Monte Millan Maria , Álvarez Enrique , Jerez Gilarranz Yolanda , Roche Marta , Taylor Clive R. , Martin Miguel 
Published: June 2022

569 Background: Taxane and platinum (TP) NAC regimens, e.g. Carboplatin and Docetaxel (CbD), in TNBC are currently of great interest, having good pathologic complete response (pCR) rates but with a significantly more manageable toxicity profile compared to anthracycline-based NAC regimens. Forkhead Box C1 (FOXC1), a transcriptional driver of cell plasticity/partial EMT/metastasis is an established mesenchymal marker diagnostic of basal-like breast cancer having proven prognostic value, but of uncertain predictive value. We sought to evaluate the potential of FOXC1 in predicting pCR to neoadjuvant TP regimens in patients diagnosed with TNBC. Methods: Pre-NAC tumor biopsy FOXC1 mRNA expression status was correlated with rate of pCR in a pooled, ambispective cohort (prospective cohort GEICAM/2006-03, NCT00432172 pooled with multi-institutional retrospective cohort, n = 119). A specific FOXC1 mRNA expression cutoff value was derived to maximize Negative Predictive Value (NPV) and Sensitivity for pCR prediction. The pCR-predictive ability of FOXC1 mRNA expression was then assessed in two validation cohorts of evaluable patients who had been enrolled in prospective clinical trials (UCONN/FIOCRUZ, n = 222, HGUGM, NCT01560663, n = 221). All evaluated patients had been diagnosed with TNBC and had received a Taxane plus Platinum-based NAC regimen. Results: FOXC1 mRNA expression was associated with pCR in CbD/TP treated TNBC patients with pCR rates of 43.48%, 47.89% and 52.73% observed in the discovery and two validation cohorts (two tailed T-test p-values of 0.0005, 0.002, 0.009, respectively). FOXC1 expression above the pre-determined cutoff value was associated with pCR to CbD/TP NAC in patients diagnosed with TNBC in both validation cohorts (OR 4.894, 1.504-15.924; p = 0.004 and OR 2.293, 1.208-4.352; p = 0.006). Conclusions: We report the retrospective validation of pre-NAC breast cancer biopsy FOXC1 mRNA expression for predicting efficacy of CbD/TP NAC in two independent, prospectively accrued TNBC patient cohorts. The described strategy may be acceptable for patient stratification to guide CbD/TP NAC recommendations in TNBC. FOXC1 mRNA or protein expression, assessed using qRT-PCR or routine immunohistochemistry (IHC), respectively, could potentially be utilized in future fixed-arm/adaptive clinical trials to further optimize NAC efficacy, in terms of achieved pCR rates, and to extend disease-free survival in patients diagnosed with TNBC.
miR-150 expression in breast cancer attracts and activates immune cells, and is associated with better patient outcome.
Authors: Oshi Masanori , Maiti Aparna , Wu Rongrong , Tokumaru Yoshihisa , Murthy Vijayashree , Yan Li , Ishikawa Takashi , Endo Itaru , Hait Nitai , Takabe Kazuaki 
Published: June 2022

570 Background: MicroRNA (miRNA) epigenetically regulate a large number of cancer-related genes and is known as a key player in cancer biology. MiR-150 promote cancer cell proliferation, migration, and invasion. However, there has been no study that investigated the role of miR-150 in the tumor microenvironment (TME) of breast cancer patients. Methods: Total of 1,961 breast cancer patients from multiple independent large cohorts were analyzed. These observational results were validated by in vitro experiments. Lymphocyte attraction was assessed using Transwell system. Results: miR-150 expression was the highest in triple negative breast cancer (TNBC) among subtypes and correlated with Nottingham histological grade (all p<0.001). A high miR-150 was significantly associated with better overall survival (OS) in both METABRIC and TCGA cohorts regardless of subtypes (all p<0.05 except for TNBC in TCGA). MiR-150 expression was strongly correlated with Hallmark immune-related gene sets (Allograft rejection, IL6 signaling, IFN-γ response, Inflammatory response, IL2 signaling, and apoptosis), with cytolytic activity, with infiltration of CD8+ T cells, CD4+ memory T cells, and dendritic cells, as well as with gene expressions of major immune checkpoint molecules (PD-1, CTLA4, IDO1, TIGIT, BTLA, and LAG3), consistently in both METABRIC and TCGA cohorts (all r>0.65, p<0.01). Unexpectedly, overexpression of miR-150 by mimic did not increase growth, migration, nor invasion of neither MDA-MB231 or BT-549 breast cancer cell lines. On the other hand, overexpression of miR-150 in either MDA-MB231 or BT-549 significantly increased attraction of lymphocyte cell line (Jurkart cells), which was abolished by addition of miR-150 inhibitor. By comparing the gene expression profile between miR-150 overexpressed and control cells, we found that many inflammation related gene sets including NF-kB signaling that enhance cell migration was enriched to miR-150 overexpressed cells, implicating that is how miR-150 high cells attract lymphocytes to TME. Conclusions: miR-150 expression is associated with immune cell infiltration and immune response, as well as with better survival in breast cancer patients. Overexpression of miR-150 in breast cancer cells did not promote cancer cell proliferation, migration, nor invasion; however, increased attraction of lymphocytes. Multiple inflammation-related genes were expressed higher in miR150 overexpressed MDA-MB231.