bluuebunny/crossref_metadata_2025_split huggingface dataset:
Romidepsin (HDACi) plus cisplatin and nivolumab triplet combination in patients with metastatic triple negative breast cancer (mTNBC).
Authors: Sharma Priyanka , Abramson Vandana G , O'Dea Anne , Nye Lauren Elizabeth , Mayer Ingrid A. , Crane Gregory James , Elia Manana , Yoder Rachel , Staley Joshua M , Schwensen Kelsey , Finke Karissa , Heldstab Jaimie , LaFaver Stephanie , Prager Micki , Williamson Stephen K. , Phadnis Milind , Reed Gregory A , Kimler Bruce F. , Khan Qamar J. , Godwin Andrew K. 
Published: June 2021

1076 Background: Histone deacetylase inhibitors (HDACi) upregulate genes involved in antigen presentation machinery and increase expression of natural killer group 2, member D ligands (NKG2DL), thus resulting in enhanced tumor cell recognition and response to PD-1/CTLA-4 blockade. Cisplatin and HDACi combination synergistically induces cytotoxicity, apoptosis, and DNA damage. This phase I-II trial investigated combination of romidepsin (HDACi) plus cisplatin and nivolumab (PD-1 inhibitor) in mTNBC. Patients and Methods: Eligible patients had mTNBC with any number of prior chemotherapies. Phase I was 3+3 dose-escalation design with three dose levels of romidepsin (8, 10, 12mg/m2, D2, 9) plus cisplatin 75mg/m2 D 1 every 21 days. Phase II treatment included romidepsin plus cisplatin plus nivolumab 360mg every 21 days and was designed according to Simon’s two stage minimax design. Primary endpoints were recommended phase 2 dose (RP2D) and objective response rate (ORR). Additional endpoints included safety, PFS, and pharmacokinetics. Results: 51 patients were enrolled (N=13 phase I, N=38 phase II) between 2015-2020. 69% had received ≥1 prior metastatic chemotherapy, 47% had prior platinum, 53% had liver metastasis, 12% had BRCA1/2 mutation, and 11% had PD-L1 positive disease. There were no dose limiting toxicities in phase I. The RP2D was romidepsin 12mg/m2 D2,9 + cisplatin 75mg/m2 D1 + nivolumab 360mg D1 every 21 days. Thrombocytopenia (G3:27%, G4:0%), neutropenia (G3:25%, G4:0%), anemia (G3:22%, G4:0%), nausea (G3:22%, G4:0%), and vomiting (G3:20%, G4:0%) were the most common grade 3/4 adverse events. 21% of patients had immune AEs (G3-4:8%). Among 34 evaluable phase II patients, ORR was 44% (Table), median PFS was 4.4 months, and 1-year PFS was 23%. Median OS was 10.3 months and 1-year OS was 43%. No pharmacokinetic interactions were detected with co-administration of romidepsin-cisplatin-nivolumab. Conclusions: The triplet combination of romidepsin plus cisplatin and nivolumab was well tolerated and shows encouraging efficacy in pretreated mTNBC, including in patients with PD-L1 negative disease and in those with liver metastasis. Correlative biomarker work is ongoing. This combination warrants further evaluation in larger studies. Clinical trial information: NCT02393794 .[Table: see text]
A phase 2 study of pamiparib in the treatment of patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation.
Authors: Sun Tao , Shi Yanxia , Cui Jiuwei , Yin Yongmei , Ouyang Quchang , Liu Qiang , Zhang Qingyuan , Chen Yiding , Zhimin Shao , Wang Shouman , Wang Xiaojia , Tong Zhongsheng , Zhong Yahua , Yan Min , Yan Xi , Wang Chuan , Yang Haiyuan , Li Miao , Xiang Xiao , Xu Binghe 
Published: June 2021

1087 Background: Breast cancer is the most common cancer among women, with up to 37% of patients (pts) harboring germline BRCA1/2 mutations (g BRCA1/2m) that appear to be sensitive to poly (ADP-ribose) polymerase proteins 1 and 2 (PARP1/2) inhibition. Pamiparib is an orally administered selective PARP1/2 inhibitor that has the potential to cross the blood-brain barrier. This study evaluated the efficacy and safety of pamiparib in pts with locally advanced/metastatic human epidermal growth factor receptor 2-negative (HER2-) breast cancer, with deleterious or suspected deleterious g BRCA1/2m, who received ≤ 2 prior lines of chemotherapy. Methods: In this open-label, phase 2, multi-center study in China (NCT03575065), pts with locally advanced/metastatic HER2- breast cancer with deleterious or suspected deleterious g BRCA1/2m triple negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2- breast cancer (HR+ cohort) were enrolled. Pts received pamiparib 60 mg orally twice daily in 28-day cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DOR) and progression free survival (PFS) by IRC, overall survival (OS), safety and tolerability. Results: 88 pts were enrolled (median age 45.5 years), 76 pts (TNBC cohort n = 55; HR+ cohort n = 21) had measurable disease at baseline per IRC. 60 pts (68.2%) received 1 or 2 prior lines of chemotherapy; 42 pts (47.7%) were treated with platinum previously. Median follow-up was 13.77 months (TNBC cohort, 10.87 months; HR+ cohort, 18.45 months). In the TNBC cohort: confirmed ORR was 38.2% (95% CI: 25.4–52.3); median DOR (mDOR) was 6.97 months (95% CI: 3.94–not estimable[NE]); median PFS (mPFS) was 5.49 months (95% CI: 3.65–7.33); median OS (mOS) was 17.08 months (95% CI:13.70–NE). In the HR+ cohort: confirmed ORR was 61.9% (95% CI: 38.4–81.9); mDOR was 7.49 months (95% CI: 5.55–14.75); mPFS was 9.20 months (95% CI: 7.39–11.93); mOS was not reached (NR; 95% CI 18.10–NE). ≥ Grade 3 treatment emergent adverse events (TEAEs) occurred in 54 pts (61.4%); anemia was the most common TEAE, occurring in 77 pts (87.5%). Dose reduction due to TEAEs occurred for 57 pts (64.8%); discontinuations due to TEAEs occurred for 2 pts (2.3%). Conclusions: Pamiparib showed a promising response in pts with locally advanced/metastatic HER2- breast cancer with a g BRCA1/2m. The safety profile of pamiparib was considered acceptable and was generally consistent with therapies in the same class. Clinical trial information: NCT03575065 .[Table: see text]
Clinical outcomes in patients (pts) with a history of central nervous system (CNS) metastases receiving talazoparib (TALA) or physician’s choice of chemotherapy (PCT) in the phase 3 EMBRACA trial.
Authors: Litton Jennifer Keating , Ettl Johannes , Hurvitz Sara A. , Martin Miguel , Roche Henri , Lee Kyung-Hun , Goodwin Annabel , Usari Tiziana , Lanzalone Silvana , Guenzel Carolin , Blum Joanne Lorraine , Rugo Hope S. 
Published: June 2021

1090 Background: In the EMBRACA trial (NCT01945775) of pts with germline BRCA1/2-mutated HER2-negative locally advanced/metastatic breast cancer (ABC), the poly(ADP-ribose) polymerase (PARP) inhibitor TALA significantly improved progression-free survival (PFS) vs PCT (8.6 vs 5.6 mo; HR [95% CI] 0.54 [0.41-0.71]; P < 0.0001). Patient-reported outcomes favored TALA, and most common adverse events included anemia, fatigue, and nausea. Previous subgroup analyses found that pts with a history of CNS metastases had improved PFS for TALA vs PCT (HR [95% CI] 0.32 [0.15-0.68]; P = 0.0016) and improved objective response rate (ORR) 63.2% vs 15.8%, respectively (odds ratio [95% CI] 8.95 [1.86-52.26]; P = 0.0013). This retrospective subgroup analysis further explored the clinical characteristics and outcomes in pts with a history of CNS metastases in EMBRACA. Methods: Pts were randomized 2:1 to TALA or PCT. Pts with adequately treated and stable CNS metastases not requiring corticosteroids were included. This analysis assessed intracranial ORR and best overall response (BOR) based on investigator assessment per RECIST 1.1 in pts with intracranial disease at baseline (data cutoff 15-Sep-17), and overall survival (OS; data cutoff 30-Sep-19). Results: In the intent-to-treat (ITT) population, 63 pts (43/287 [15.0%] TALA and 20/144 [13.9%] PCT) had a history of CNS metastases, of which 33 (11.5%) pts (TALA) and 15 (10.4%) pts (PCT) had intracranial disease at baseline. Additional baseline characteristics are shown in the table. Intracranial ORR in pts with intracranial disease at baseline and unconfirmed complete or partial response was 18.2% (TALA) vs 20.0% (PCT) (odds ratio [95% CI] 0.78 [0.13-5.80]; P = 0.765). In pts with intracranial disease at baseline, an intracranial BOR of stable disease was 69.7% for TALA vs 33.3% for PCT. Median OS in pts with a history of CNS metastases was 12.9 mo (95% CI 9.4-15.6) for TALA and 13.4 mo (95% CI 8.8-17.6) for PCT (HR [95% CI] 0.67 [0.37-1.2]; P = 0.1936 [stratified log-rank test]). In the safety population ([n = 43, TALA]; [n = 19, PCT]), median treatment duration (range) with TALA was 5.0 (0.1-36.0) mo compared with 2.1 (0.4-6.9) mo for PCT. Conclusions: In this subgroup analysis, baseline characteristics between pts with a history of CNS metastases treated with TALA or PCT were comparable. More pts with intracranial disease at baseline treated with TALA vs PCT experienced stable disease. Intracranial ORR in pts with intracranial disease was 18.2% for TALA vs 20.0% for PCT. Treatment options for pts with a history of CNS metastases are limited and further investigation in larger data sets is warranted. Clinical trial information: NCT01945775 .[Table: see text]
Systemic chemotherapy in patients with brain only metastatic breast cancer: A retrospective analysis.
Authors: Puri Akshjot , Mylavarapu Charisma , Ensor Joe E. , Parveen Parveen , Tremont-Lukats Ivo , Chang Jenny Chee Ning , Niravath Polly Ann 
Published: June 2021

1093 Background: The treatment of patients with brain only metastatic breast cancer (BO-MBC) remains very challenging. There is also very limited literature informing on appropriate treatment or natural history of this entity. Systemic chemotherapy in addition to targeted therapy and/or anti-estrogen treatment is often used, but little is known if it adds to the overall or disease free survival. In this retrospective study, we examine this, as well as other factors which may be associated with increased risk of CNS or systemic recurrence in these patients. Methods: A database search at a single institution identified 178 patients with brain metastases (BM) from breast cancer out of which 45 patients had BO-MBC between 2007-2020. We collected demographic, clinical, radiographic and other treatment data. Leptomeningeal disease (LMD) was diagnosed by cerebrospinal fluid (CSF) cytology, neuroimaging, or both. We used the Brookmeyer and Crowley method. Results: The patients were followed for a median of 17.9 months; 36 out of 45 patients (80%) received local treatment for BM (surgery/radiation/both) and HER2 directed antibodies or tyrosine kinase inhibitors and/or anti-estrogen treatment, whereas 9 out of 45 patients (20%) received systemic chemotherapy in addition. There were 22 out of 45 (49%) HER2 +, 5 out of 45 (11%) HR + and 18 out of 45 (40%) triple negative breast cancer (TNBC) patients. There were 17 out of 45 patients (38%) who were deemed to have low burden of BM (defined as one to three BM and largest being ≤3 cm) whereas there were 24 out of 45 patients (53%) who had high burden of BM (defined as four or more BM or largest being > 3 cm). Conclusions: Patients with BO-MBC represent a distinct entity. Despite having better survival than patients with BM and extra CNS disease these patients have a high risk of developing LMD, CNS and systemic recurrences. The addition of chemotherapy to targeted therapy and/or anti-estrogens does not decrease the rates of systemic or CNS recurrence. The ER+ subset have a lower rate of development of systemic disease, as expected due to their relatively indolent biology. The CNS and systemic recurrence seem to be higher in patients with HER2+ cancers and counterintuitively even in those with low burden of BM; albeit these were statistically insignificant.[Table: see text]
Digital footprint of hematology-oncology fellowship programs: Identifying gaps after the first virtual recruitment season.
Authors: Velazquez Manana Ana I. , Abuali Inas , Rodriguez Vargas Juan J. , Aslanova Minira , Molina Aponte Yaniris , Romero Ramos Yaideliz , Duma Narjust 
Published: June 2021

11003 Background: The COVID-19 pandemic has led to unprecedented restrictions to travel and in-person activities that limit hematology/oncology (HO) fellowship programs’ (FP) recruitment activities. Prospective applicants rely on websites and social media (SOME) to guide their decisions of applying or ranking a FP. We aim to evaluate HO FP’s digital footprint in order to identify informational gaps. Methods: The AMA Fellowship and Residency Electronic Interactive Database (FREIDA) was queried for all HO programs. We searched Google, Twitter, Instagram, Facebook, and YouTube for HO FP pages. Content was evaluated using published criteria. Qualitative content analysis of SOME posts is planned. Results: Our analysis includes 176 FP that actively recruited during the 2020 match season. Over half (57%, n = 100) were university-based and the median number of fellow positions per year was 4 per FP (range 0-16). Most FP had websites (95%, n = 167) with varying information (Table) for prospective applicants. Twenty percent (n = 33) included a diversity statement. While 63% (n = 106) of FP provided application information, only 51% discussed visa requirements. Few FP websites included key information such as why fellows chose a particular FP (7%, n = 12), accolades of fellows (3%, n = 5), or employment location of alumni (25%, n = 44). Only 42% (n = 69) provided city, and 5% (n = 8) showed fellows socializing. Thirty-four FP (19%) have informational videos (range 1-10) in YouTube (length range: 1:37-18:15min). Most (82%; n = 28) were published since May 2020 in alignment with the FP recruitment season. Twitter was the second most common SOME platform, used by 19% (n = 32) of FP. 56% (n = 18) joined Twitter since May 2020 correlating with the current recruitment season. The number of Twitter followers (median 119, range: 0-1408) and posts (median 47, range: 0-687) varied across FP. Only 4% used Facebook and 6% Instagram. Conclusions: Our analysis of FP’s digital footprint revealed that applicants participating in the 1st virtual HO recruitment season were provided limited online information. Programs can use online content to provide information on resources, research opportunities, and achievements of faculty and fellows that can guide applicant decision making. In the era of COVID-19, highlighting the diversity and breath of each FP, hospital, and city are vital to attract a diverse and talented pool of trainees.[Table: see text]
Minding the gap: Gynecologic oncology practices differ by gender.
Authors: Temkin Sarah Madhu , Chapman Eloise , Kohn Elise C. , Nair Navya , Blank Stephanie V. 
Published: June 2021

11011 Background: Although most gynecologic oncologists (GOs) are now women, gender differences in clinical practice and compensation persist. Practice characteristics and infrastructural support that may influence gender-based differences were explored. Methods: Every 5 years, the Society of Gynecologic Oncology (SGO) conducts a member survey that provides details on member demographics, practice characteristics, activities, and revenue. Between 8/15-9/30/19 SGO members received a direct link to the survey. Gender was self-identified. Differences in responses were evaluated by gender. Results: Of 1425 surveys delivered, 690 were completed (48% response rate). 312 (45%) identified as male; 367 (53%) as female; 1 nonbinary; 1 other; 7 no response. Male GOs were more likely white (75 vs 68%, p=0.048), married (91 vs 81%, p<0.001), heterosexual (94 vs 90%, p=0.045), and hold an academic rank of professor (23 vs 12%, p<0.001). Practice setting and number of partners were similar. Chemotherapy prescribing was more common for females (82 vs 73%, p=0.004), but other clinical activities were similar (Table). Female GOs had lower clinical volumes than males for cervical, ovarian, vaginal/vulvar cancer and benign gynecologic procedures. Females reported fewer medical assistants and transcriptionists supporting their clinical activities. Overall and practice support was higher for male GOs although hospital support was similar for both genders. Female GOs reported more time spent on research (26 vs 19%, p=0.005), but the same research support. Conclusions: Clinical activities, specifically chemotherapy prescribing, and support differ for male and female GOs and may explain gender inequities. Clinical support should be equalized to maximize workplace productivity regardless of gender. Coordination of support between the practice and hospital and standard compensation for chemotherapy prescribing could decrease the large gender wage gap in this specialty.[Table: see text]
Supporting the mental well-being of healthcare professionals during a pandemic.
Authors: Lopez Ana Maria , Capparella Lisa , Pomerantz Miriam , Naputo Kristine , Leader Amy , O'Hayer C. Virginia Virginia 
Published: June 2021

11037 Background: Burnout amongst healthcare professionals has been well-documented as a phenomenon that compromises the quality and viability of patient-centered care, particularly in oncology. Due to the extraordinary demands of the pandemic, burnout has emerged as a public health crisis that warrants immediate attention to preserve the wellbeing of healthcare staff. At the onset of the pandemic, The Sidney Kimmel Cancer Center (SKCC) at Jefferson, an urban NCI-designated cancer center, translated its support offerings to virtual events. Initially, healthcare providers (HP) sought support by attending patient programs. In response, SKCC initiated virtual programming to support the well-being and needs of the HP team. Methods: Within weeks of the state shutdown due to the pandemic, programs were initiated to address HP self-reported distress: Coping Effectively and Mindfulness Moments Each 30-minute session was facilitated by a licensed psychologist and social worker. Coping Effectively offers strategies from evidence based treatment including Dialectical Behavior Therapy, Acceptance and Commitment Therapy, and Cognitive Behavioral Therapy, to cope with distress and burnout. Mindful Moments draws from Mindfulness Based Stress Reduction practices including observing breath and guided meditations. These programs have been offered consistently throughout the pandemic. Schwartz Rounds, geared towards supporting the human side of healthcare, provided “hot” topic moderated discussions, four of which focused on the pandemic These discussions allow for HP to come together to discuss difficult topics and emotions impacting a variety of professionals. All programming was evaluated with a single question to measure the impact of the session on reducing distress. Each program began and ended with a poll asking, “How distressed do you currently feel?” Attendees respond on a Likert scale from 0 to 10, in which10 indicated the highest level of distress. Results: Since March 31st, 340 staff have attended Mindful Moments and 236 staff have attended Coping Effectively. From March 2020-February 2021, 382 attendees measured their distress before and after attending a staff program. Schwartz Rounds hosted 471 HP from a variety of disciplines. Participants were asked to complete an evaluation following rounds. 31% of program participants’ completed an evaluation form and 89% rated the program exceptional/very good. Conclusions: Despite the challenges of COVID-19, the pivot to virtually create programs to support staff during the pandemic was swift and thoughtful. The increased attendance and the feedback from evaluations are promising indicators of decreasing burnout amongst HP. How Distressed do you Currently Feel? (Average Score scale 1-10)[Table: see text]
PD1 inhibition in soft-tissue sarcomas with tertiary lymphoid structures: A multicenter phase II trial.
Authors: Italiano Antoine , Bessede Alban , Bompas Emmanuelle , Piperno-Neumann Sophie , Chevreau Christine , Penel Nicolas , Bertucci Francois , Toulmonde Maud , Bellera Carine A. , Guegan Jean-Philippe , Sautes-Fridman Catherine , Bougoüin Antoine , Cantarel Coralie , Le Loarer Francois , Blay Jean-Yves , Fridman Wolf-Herman 
Published: June 2021

11507 Background: PD1 inhibition has shown limited activity in all comers clinical trials including patients with advanced soft-tissue sarcomas (STS). In the PEMBROSARC study, objective response rate, progression-free (PFS) and overall survival (OS) were respectively 2.1%, 1.4 and 7.1 months respectively (Toulmonde et al. Jama Oncol 2017). We have recently shown that the presence of tertiary lymphoid structures (TLS) may represent a biomarker to select patients who are more likely to benefit from immunotherapy (PetitPrez et al., Nature 2020). We report here the first clinical trial investigating the efficacy of PD1 inhibition in TLS-positive STS. Methods: PEMBROSARC is an open-label multicenter phase II study of pembrolizumab in combination with low-dose cyclophosphamide in pts with STS selected based on the presence of TLS. TLS status has been assessed centrally has previously described (PetitPrez et al., Nature 2020). Eligible patients received pembrolizumab 200mg IV q21 days and cyclophosphamide 50 mg BID 1week on, 1 week off. All patients had confirmed progressive disease at inclusion based on central review of two imaging performed at less than 6 months interval. The primary efficacy endpoint was 6-month non-progression (as per RECIST evaluation criteria v1.1). Based on the following hypotheses: 15% 6-month non-progression rate (H0), 40% acceptable 6-month non-progression rate (H1), 5% type I error rate, 90% power, a total of 29 assessable patients were necessary and 8 patients or more had to be progression-free at 6 months to reach the first endpoint. Results: 240 patients were screened for TLS status between September 2018 and January 2020 in 7 centers of the French Sarcoma Group. Among them, 48 were found to be TLS+ as per central review and 35 were included in the study. The three most frequent histological subtypes were: well-differentiated/dedifferentiated liposarcoma (n = 13); UPS (n = 6), and leiomyosarcoma (n = 4). 30 patients were eligible for efficacy. Of those, as per central imaging review, 13 patients (43.3%) had tumor shrinkage resulting in partial response in 8 patients (26.7%) and stable disease in 5 cases (16.7%). 10 patients had progressive disease. Twelve patients were progression-free at 6 months (40.0% 95%CI = [22.7 – 59.4]).Median PFS and OS were 4.1 months (95%CI, 1.4-9.6) and 14.5 months (95%CI, 8.5- 18.3 months), respectively. Conclusions: With an objective response and a 6-month non-progression rates of 26.7% and 40% respectively versus 2.1% and 4.2% in all comers, the PEMBROSARC study confirms that selection based on TLS status is an efficient approach to tailor immunotherapy in STS patients. Clinical trial information: NCT02406781.