bluuebunny/crossref_metadata_2025 huggingface dataset:
MONARCH 2: Subgroup analysis of patients receiving abemaciclib + fulvestrant as first- and second-line therapy for HR+, HER2- advanced breast cancer.
Authors: Neven Patrick , Johnston Stephen R. D. , Toi Masakazu , Sohn Joohyuk , Inoue Kenichi , Pivot Xavier , Burdaeva Olga Nikolaevna , Okera Meena , Masuda Norikazu , Koh Han A. , Grischke Eva-Maria , Conte Pier Franco , Lu Yi , Haddad Nadine , Hurt Karla , Kaufman Peter A. , Llombart-Cussac Antonio , Sledge George W.
Published: May 2020

1061

Background: In MONARCH 2 (M2), abemaciclib (A), an oral selective cyclin dependent kinase 4 & 6 inhibitor, + fulvestrant (F) demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to placebo (P) + F in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC). Numerically more pronounced PFS & OS improvement was noted in subgroups (Sub) with visceral (V) disease and primary endocrine resistance. Here we report efficacy data for M2 with respect to 1L and 2L Sub (last line of endocrine therapy [ET] in (neo)adjuvant and metastatic setting, respectively). Methods: M2 (NCT02107703) was a global, randomized, double-blind Phase 3 trial of A+ F (N = 446) or P + F (N = 223) in women with ET resistant (ETR) HR+, HER2- ABC regardless of menopausal status. Patients (pts) were stratified by site of metastasis (V, bone-only, or other) and resistance to prior ET (primary vs secondary). Exploratory Sub analyses of PFS and OS were conducted among pts in the ITT population with 1L vs 2L. Hazard ratios (HR) were estimated using Cox models with a test of interactions of Sub with treatment performed. Results: At data cut-off (June 20th, 2019), the effect of A + F vs P + F was consistent across 1L (N = 265/133) and 2L (N = 170/86) Sub, with no statistically significant interaction for PFS (p = 0.341) or OS (p = 0.265). For 1L pts, improvements in PFS (HR: 0.57; 95% CI:0.45, 0.73) and OS (HR: 0.85; 95% CI:0.64, 1.14) were observed. Similar efficacy results were observed for 2L pts (PFS: HR: 0.48; [95% CI: 0.36, 0.64]; OS HR: 0.66 [95% CI: 0.46, 0.94]). The numerically largest effects in the 1L population were noted in pts with less favorable prognostic factors such as primary ETR (PFS: HR 0.40 [95% CI: 0.26, 0.63]; OS: HR 0.58 [95% CI:0.35, 0.97]) and V disease (PFS: HR 0.54 [95% CI: 0.39, 0.73]; OS: HR 0.82 [95% CI: 0.57, 1.17]). Conclusions: The statistically significant benefit observed in the M2 study was observed across 1L and 2L patients. In 1L patients (A+F Arm), improvements were observed for PFS and OS with the most pronounced effects noted in patients with less favorable prognostic factors. Clinical trial information: NCT02107703 .
A phase II study of rh-endostatin in combination with chemotherapy in human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer (ABC).
Authors: Huang Yuan , Zheng Ya-bing , Cao Wen-Ming , Chen Zhan-hong , Fu Jianfei , Li Gang , Jia Wang Xiao
Published: May 2020

1071

Background: There is an urgent need to improve the efficacy of chemotherapy for HER-2 negative patients (pts) who lack anti-HER-2 therapies. Rh-Endostatin (endostar), a recombinant human endostatin, is a potent inhibitor of angiogenesis. This single-arm multicenter phase 2 study was designed to assess the efficacy and safety of endostar combined with chemotherapy in HER-2 negative ABC. Methods: Eligible pts had HER-2 negative inoperable locoregionally recurrent or metastatic breast cancer and an ECOG PS of 0 or 1. Pts with either measurable or nonmeasurable disease were eligible. Endostar (15 mg/m2, continuous infusion, day 1-7) plus chemotherapy were administered every 21 days until disease progression, intolerable toxicity or other reasons. Chemotherapy regimens were selected by investigators based on clinical decision. Primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). Results: From August 2016 to December 2019, 40 female pts were enrolled in 3 centers. The median age was 52. Ten pts were previously untreated and 30 pts had at least 1 line of chemotherapy for advanced disease. 31 pts were triple negative BC (TNBC) and 9 pts were hormonal receptor positive (HR+). Platinum combined with paclitaxel or gemcitabine were administered with endostar in 55% of pts. Others received paclitaxel or gemcitabine combined with endostar. 12 pts achieved a best response of partial response (PR) and 13 pts had stable disease (SD). Among 30 pts with measurable disease, ORR was 40% and DCR was 83%. The ORR for patients treated as the first-line therapy was 75% while as the second line or beyond was 27%. For TNBC and HR+ BC pts, the ORR was 46% and 17% respectively. Median PFS was not reached after a median follow-up of 7.6 months. The most common Grade 3/4 AEs observed during this study were neutropenia (10%), leukopenia (10%) and thrombocytopenia (5%). Conclusions: Endostar combined with chemotherapy was effective and well tolerated for the treatment of HER-2 negative ABC, especially TNBC. Its efficacy and safety could be further studied in randomized trials. Clinical trial information: NCT03907098 .
Preliminary safety and efficacy of GX-I7, a long-acting interleukin-7, in combination with pembrolizumab in patients with refractory or recurrent metastatic triple negative breast cancer (mTNBC): Dose escalation period of Phase Ib/II study (KEYNOTE-899).
Authors: Sohn Joohyuk , Park Kyong Hwa , Ahn Hee Kyung , Lee Keun Seok , Kim Jee Hyun , Kim Sung-Bae , Lee Kyoung Eun , Kim Jee Hung , Yang Se Hwan , Le Ngocdiep T. , Kim Jiwon , Heo MinKyu , Woo Jung-Won , Sung Young Chul , Im Young Hyuck
Published: May 2020

1072

Background: Pembrolizumab monotherapy did not significantly improve OS as 2nd and 3rd-lines treatment for mTNBC compared to standard chemotherapy in phase III study (KEYNOTE-119) leading to high unmet needs of effective treatment. Recent studies showed that higher lymphocyte count is an independent factor which correlates with better response to checkpoint blockade in cancer patients. GX-I7, a long-acting interleukin-7, could potentially provide synergistic anti-tumor efficacy with pembrolizumab by increasing number of T cells both in tumor microenvironment (TME) and peripheral blood (PB). Methods: This is an open-label, phase Ib/II study in patients with refractory or recurrent TNBC who failed from standard chemotherapy in the metastatic setting, with ≤3rd-lines of previous chemotherapy. The dose escalation phase adopted the 3+3 design. The GX-I7 doses were administered IM q9w or q12w, with or without cyclophosphamide pre-conditioning depending on the allocation, and in combination with pembrolizumab 200 mg IV q3w. The objectives were dose limiting toxicities (DLTs), safety, pharmacodynamic markers including lymphocyte increase and RP2D. Results: As of January 30, 2020, GX-I7 and pembrolizumab were exposed to 24 patients (median age 46.0 years [29-75], ECOG PS 1 [58.3%], median cycle no. 3 [1-9]). Treatment was discontinued in 13 (54.2%), majority due to PD and 11 patients are ongoing. No DLTs were reported in all dose groups. Treatment related AEs occurred in 91.7% of patients with grade 1-2 and 9.1% with grade 3 (no grade 4). Common AEs were injection site reaction (39.0%) and fever (13.0%), which were easily managed. Grade 3 toxicity were AST/ALT elevation and infusion related reaction, reported from 1 patient each (4.2%). GX-I7 induced dose-dependent lymphocyte proliferation in PB, with approximately 4-folds increase in high doses. 17 patients were evaluable; confirmed objective responses from ongoing patients included one partial response (5.9%), 2 stable disease (11.8%) and 1 durable unconfirmed PD (5.9%). Conclusions: GX-I7 in combination with pembrolizumab was well tolerated, with no DLTs reported. There was no apparent increase of immune-related AEs with the addition of GX-I7. Pharmacodynamics data support proof of mechanism and it warrants further clinical studies. Clinical trial information: NCT03752723 .
Dual anti-CTLA-4 and anti-PD-1 blockade in metaplastic carcinoma of the breast: Dart (SWOG S1609, Cohort 36).
Authors: Adams Sylvia , Othus Megan , Patel Sandip Pravin , Chae Young Kwang , Miller Kathy , Chugh Rashmi , Schuetze Scott , Sharon Elad , Korde Larissa A. , Gray Robert James , Mayerson Edward , Plets Melissa , Kurzrock Razelle
Published: May 2020

1073

Background: Immune checkpoint blockade, specifically anti-CTLA-4 and anti-PD-1-directed approaches, has improved outcomes in various tumors and is being tested in SWOG S1609 in rare solid tumors (DART=Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors). Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer with poor response to cytotoxics and median survival of < 1 year for metastatic disease. A MpBC stratum was added based on promising activity of immunotherapy in a patient with MpBC (Adams, npj Breast Cancer 2017). Here, we report the MpBC cohort of S1609 DART. Methods: In this prospective, open-label, multicenter phase II trial patients received ipilimumab (1mg/kg q6 weeks) plus nivolumab (240mg intravenously every 2 weeks). Eligibility for cohort 36 required histologically confirmed MpBC, measurable disease, and ECOG PS 0-2. Prior anti-CTLA4 or anti-PD-1/PD-L1 treatment (but not both) was permitted as well as treated brain metastases. The primary endpoint was overall response rate (ORR, confirmed CR, PR) by RECIST v1.1; 2 or more responses in 16 patients was considered a success. Secondary endpoints: toxicity (CTCAE v4.0), PFS and ORR by immune-related RECIST (iRECIST), overall survival (OS). Biomarker analyses are ongoing. Results: Nineteen patients were registered to the cohort and seventeen eligible patients received therapy. The median age was 60 (range 26-85), most tumors were high grade, triple negative and had a high ki67 (median 87%), median prior therapy = 2 lines. The ORR was 12% (RECIST 1.1) and 18% (iRECIST), with ongoing responses at 23, 18 and 11 months, respectively; SD was seen in 24%, none > 6 months (Table). Median OS was 12 months. AEs were observed in 11 patients (65%), with 3 patients (18%) having Grade 3/4 AEs and 1 patient with a fatal AE (myocarditis). The most common toxicities were LFT abnormalities and fatigue. Conclusions: Cohort 36 met its primary endpoint: ipilimumab plus nivolumab was clinically active in advanced MpBC, with durable responses observed in 3/17 patients. Further investigation of this combination is warranted. Clinical trial information: NCT02834013 . [Table: see text]
Translational relevance of androgen receptor immunohistochemistry scoring systems for data harmonization in triple negative breast cancer (TNBC).
Authors: Mufti Suhail Sayeed , Lalkota Bhanu Prakash , BN Tejaswini , Varayathu Hrishi , Sarathy Vinu , Puii Lalnun , Sangi Lalram , Thomas Beulah Elsa , Hazarika Diganta , Thungappa Satheesh Chiradoni , Bj Sriniivas , Patil Shekar , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah
Published: May 2020

1078

Background: Androgen receptor (AR) expressing triple negative breast cancer (TNBC) is a sub-set of TNBC with an evolving prognostic and predictive behaviour. AR immunohistochemical threshold for positivity has not been standardized and a wide range of cut-offs have been used across studies ( > 0% to 75%). In this study we explored AR immunohistochemistry thresholds in relation to disease free survival (DFS) and clinical outcomes in non-metastatic TNBC using the Allred and H-Score systems. Increasing interest in AR as a therapeutic target for TNBC and the use of digital tissue image analysis makes it important to standardize AR immunohistochemistry reporting. Methods: 100 FFPE (formalin-fixed paraffin-embedded) tumour blocks were retrieved for non-metastatic TNBCs diagnosed between January 2015 and May 2017 and immunostained using AR441 (IgG1) mouse monoclonal antibody. Clinical follow-up ranged from 59 to 31 months and DFS was calculated. Cut-off scores were explored using Evaluate Cutpoints ( R maxstat package) and X-tile software. The score with maximum split in DFS (based on log-rank statistics and lowest p-value) was chosen as the cut-off. Descriptive and survival statistics was performed. Results: The median age was 51 (SD 11.262; range 28 to 82) years. Using Evaluate Cutpoints ≥3 was found as the threshold for AR by Allred Score. 36% cases were AR positive using Allred score (HR 0.508; CI 0.234 - 1.11; p-value 0.08). Using Evaluate Cutpoints ≥30 was found as the threshold for AR by H-Score (HR 0.624, CI 0.306 - 1.27; p-value 0.19). 35% cases were AR positive using H-Score. X-tile analysis also found the cut-offs as ≥3 and ≥30 for Allred and H-Score respectively (p < 0.05). A significant correlation was seen between the two scoring systems (Pearson Correlation 0.935; p < 0.01). A significantly higher number of grade III TNBCs were AR negative (n = 55/76) compared to grade II (n = 9/24) (p = 0.002). Cut-off for Ki67 was 75 (HR 1.61, CI 0.85-3.04, p-value 0.141) with a significantly higher number of AR negatives in the Ki67≥75 group (21/26; p < 0.05). The overall median DFS was 51.9 months. There was no significant difference in DFS for the AR negative (median: 47.4 months; mean: 39.39 months) and AR positive (Median survival not reached; mean: 41.3 months) groups(p = 0.23). Conclusions: AR immunohistochemistry cut-offs using the Allred (≥3) and H-Score (≥30) are close to the ones used for ER/PR immunohistochemistry as per ASCO/CAP guidelines, making a strong case for universal application of these systems for harmonization of AR data.
Clinical predictors of long-term response to capecitabine in metastatic breast cancer (MBC).
Authors: Kelly Deirdre , Lupichuk Sasha M. , Bedard Philippe L. , King Karen , Cescon David W. , Veitch Zachary William Neil
Published: May 2020

1088

Background: Select patients (pts) with metastatic breast cancer (MBC) treated with capecitabine (cape) experience long-term disease control. We aimed to evaluate the clinical and biological predictors of long-term response. Methods: Pts receiving cape monotherapy for breast cancer from 01/2006 to 01/2016 at Princess Margaret Cancer Centre in Toronto, Canada (N = 352) or Alberta, Canada (N = 798) were identified through central pharmacy records. A median time-to-progression (MTTP) 3-fold higher (19.3 months) than those seen in published studies for patients treated with cape monotherapy at 1000mg/m2 was applied to select for pts with long-term response. MBC pts meeting these criteria were identified through chart review, with collection of clinical, pathological, and survival outcomes in addition to oncologist assessed (o) best response (eg: oCR, oPR, oSD) by radiology report review. Descriptive statistics, Kaplan-Meier and Cox-regressions were applied. Results: Overall, 41 (4%) pts met long-term response criteria. Median age of the study cohort was 62 (range 40-80), with 39% metastatic at diagnosis and 76% post-menopausal. At initiation of cape, a majority of pts were HR positive (85%), with an LDH < ULN (56%), and had bone (83%) or visceral (63%) metastases. Only 1 (2%) patient was HER2+. In the metastatic setting, most patients were chemotherapy-naive (83%) and had received 0-1 lines of hormonal therapy (61%). Median treatment duration with cape was 2.2 years (range 1.7-5.7) with 37% of pts having ≥40 cycles (range 22-94). Visceral (49%), bone (34%), and lymph nodes (24%) were the most common sites of progression, with 41% requiring 1 dose reduction and 27% requiring 2 dose reductions of cape. Overall response rate was 56% (oCR = 2%, oPR = 54%) with 44% having oSD as best response. Median follow-up was 6.8 years (95%CI: 5.5-8.2). Median PFS was 2.3 years (2.0-2.6), with a median OS of 3.8 years (2.9-4.6). 5 patients (12%) remained alive at data-cutoff, and 1 (2%) remained on treatment after 94 cycles of cape. Conclusions: Clinical features associated with long-term response on cape include HR positive, HER2 negative postmenopausal patients with bone predominant metastasis who have received 0-2 lines of prior hormone therapy and 0-1 lines of chemotherapy in the metastatic setting. This is the largest reported analysis of MBC patients with prolonged responses to cape. In the absence of randomized controlled trials; real-world evidence could aid clinicians in the optimal patient selection for treatment with cape.
Veliparib (V) monotherapy (monoTx) following combination therapy with V + carboplatin/paclitaxel (CP) in patients with gBRCA-associated advanced breast cancer: Exploratory results from BROCADE3.
Authors: Han Hyo S. , Arun Banu , Kaufman Bella , Wildiers Hans , Friedlander Michael , Ayoub Jean-Pierre M. , Puhalla Shannon L , Bach Bruce Allen , Dudley Matthew , Kundu Madan Gopal , Maag David , Ratajczak Christine , Dieras Veronique
Published: May 2020

1091

Background: In BROCADE3 (NCT02163694), addition of PARP inhibitor V to CP resulted in improved progression-free survival (PFS) (HR 0.71 [95% CI 0.57−0.88], p=0.002) in patients (pts) with advanced HER2-negative breast cancer and g BRCA1/2 mutation. A subset of pts transitioned to V/placebo (PL) monoTx at an intensified dose/schedule after CP discontinuation prior to progression (investigator discretion). Here, we evaluate the impact of this transition on efficacy and safety. Methods: Pts were randomized 2:1 to CP with V (n=337) or PL (n=172). V (120 mg po BID) or PL was given on Days (D) −2 to 5, C (AUC 6) on D1, and P (80 mg/m2) on D1, 8, and 15 (21-day cycles). Pts who transitioned to monoTx received V/PL 300-400mg BID daily until progression. A Cox model with a time varying covariate indicating transition from V/PL with CP to V/PL monoTx was fit to estimate treatment effect during combination and monoTx phases. PFS by cycles of CP prior to monoTx and AEs during monoTx are summarized. Results: A subgroup of 136 (40%) and 58 (34%) pts on the V and PL arms, respectively, received monoTx. When a Cox model with a time-varying covariate was fit for PFS (per investigator), the nominal P-value for treatment by covariate interaction was 0.038. The HRs (95% CI) for V vs PL during combination therapy and monoTx were 0.81 (0.62–1.06) and 0.49 (0.33–0.73). The Table summarizes PFS by cycles of C and/or P prior to monoTx. Common AEs (>20% of pts) during V or PL monoTx were nausea (52%/10%), fatigue (23%/12%), headache (21%/17%), and diarrhea (21%/9%). Seizures (2.2%/0%) were reported during monoTx. Rates of cytopenias for V or PL monoTx were: anemia 12%/14%; neutropenia 13%/12%; and thrombocytopenia 10%/5%. Conclusions: These analyses suggest that pts treated with V + CP derive benefit from both combination therapy as well as V monoTx after CP discontinuation. Pts receiving V monoTx after ≤ 6 cycles of VCP experienced a similar benefit to those who transitioned to monoTx after 7–12 cycles of VCP, suggesting that V maintenance therapy may be suitable following a limited duration of combination therapy. Clinical trial information: NCT02163694 . [Table: see text]
Comparison of the cell-free DNA genomics in patients with metastatic breast cancer (MBC) who develop brain metastases versus those without brain metastases.
Authors: Vidula Neelima , Niemierko Andrzej , Hesler Katherine , Isakoff Steven J. , Juric Dejan , Spring Laura , Mulvey Therese Marie , Younger Jerry , Moy Beverly , Ellisen Leif W. , Bardia Aditya
Published: May 2020

1094

Background: The genomics of patients with metastatic breast cancer (MBC) who develop brain metastases (BM) is not well understood given the difficulty in obtaining brain tumor for genotyping. We compared tumor genotyping results via cell-free DNA (cfDNA) collected at MBC diagnosis in patients who developed BM after MBC diagnosis with those who did not develop BM (non-BM). Methods: Patients at an academic institution who had cfDNA testing (Guardant 360/Next generation sequencing, 73 gene assay) at MBC diagnosis between 1/2016-12/2017, with ≥ 6 months of follow-up post testing, were identified. A chart review was done to identify tumor subtype, demographics, cfDNA results, and development of BM at or after MBC diagnosis. Pearson’s chi-squared and Wilcoxon rank sum tests were used to determine differences in clinical and cfDNA characteristics in BM vs. non-BM (p<0.05 for statistical significance). Results: CfDNA results were available for 49 patients, of whom 13 (27%) developed BM (4 with BM at MBC diagnosis). The median time to BM development was 11 months. While patients with BM were younger at MBC diagnosis than non-BM (median age BM 53 vs. non-BM 61, p=0.05), they had similar subtype (BM vs. non-BM: HR+/HER2- 62% vs. 69%, HER2+ 8% vs. 14%, TNBC 23% vs. 17%, unknown 8% vs. 0%, p=0.3), de-novo vs. recurrent disease (BM vs. non-BM: de-novo 8% vs. 14%, recurrent 92% vs. 86%, p=0.6), and visceral disease (BM vs. non-BM: 77% vs. 56%, p=0.2) distributions. All patients with BM had ≥1 detectable cfDNA mutation vs. 88% of non-BM. While the median mutant allele frequency of the most common mutation was similar in BM vs. non-BM (2.4% vs. 3.7%, p=0.5), the mutation pattern varied. Patients with BM more often had mutations in BRCA1 (15% vs. 3%, p=0.1), APC (15% vs. 0%, p=0.02), and CDKN2A (15% vs. 0%, p=0.02), compared to non-BM. In 4 patients with BM at MBC diagnosis, mutations in APC (50%), CDKN2A (50%), and BRCA 1/2 (25%) were noted; 1 had coexisting APC and BRCA1/2 mutations and another had coexisting APC and CDKN2A mutations. Conclusions: Patients with MBC who develop BM may have different cfDNA genomics, particularly BRCA1, APC, and CDKN2A mutations. Further research is needed to determine the predictive value of cfDNA at MBC diagnosis in the identification of patients at higher risk of developing BM. [Table: see text]
A phase I study of SHR6390, a cyclin-dependent kinase 4/6 inhibitor in patients with advanced breast cancer (ABC).
Authors: Zhang Pin , Xu Binghe , Gui Lin , Wang Wenna , Xiu Meng , Zhang Xiao , Sun Guilan , Zhu Xiaoyu , Zou Jianjun
Published: May 2020

1095

Background: SHR6390 is a novel inhibitor of cyclin-dependent kinase 4/6 (CDK 4/6). This study was conducted to evaluate the tolerability, pharmacokinetics, safety, and preliminary antitumor activity of SHR6390 in patients (pts) with advanced breast cancer (ABC). Methods: In this open-label, single-arm phase I study, pts who had failed standard therapy were enrolled to receive oral SHR6390 in 3 + 3 dose-escalation pattern at doses of 25−175 mg. Eligible pts were given a single-dose of SHR6390 in week 1, followed by once daily continuous doses for three weeks, and one week off in 28-day cycle. Based on the tolerability, pharmacokinetics, and activity data revealed from the dose-escalation phase, three dose cohorts were selected to expand to 8−10 pts. The primary endpoints were maximum tolerated dose (MTD) and pharmacokinetics. Results: Between Apr 15, 2016 and Dec 21, 2018, 40 pts were enrolled. All pts were diagnosed of hormone receptor positive and HER2-negative ABC. 45.0% of pts had at least three prior chemotherapies and 55.0% had at least two prior endocrine therapies. SHR6390 100 mg, 125 mg, and 150 mg cohorts were expanded to 10 pts, respectively. No dose limiting toxicity was observed and the MTD was not reached. Adverse events (AEs) of grade ≥3 were observed in 22 (55.0%) of 40 pts, being neutropenia (52.5%), leukopenia (35.0%), thrombocytopenia (5.0%), and hypertension (2.5%). No serious AEs were reported. At the doses of 50−175 mg, median time to peak concentration was 2.5−4.0 h, and mean terminal half-life was 40.3−51.4 h with single-dose SHR6390. Following multiple dosing, steady state SHR6390 was observed on day 8. The steady state areas under the concentration and peak concentration increased slightly greater than the increase rate of dose, with steady state Cmax at day 21 of 41.1, 53.4, 87.0, 115.0, 126.0, and 155.0 ng/mL in 50, 75, 100, 125, 150, and 175 mg cohorts, respectively. The disease control rate was 62.5% (25/40, 95% CI 45.8% to 77.3%). Two pts (5%, one in 125 mg, one in 150 mg cohort) achieved partial response, with responses lasting 169 and 356+ days, respectively. Conclusions: SHR6390 showed acceptable safety profile and dose-dependent plasma exposure in pts with ABC. The recommended phase II dose was 150 mg. Preliminary evidence of clinical activity was observed, warranted further study. Clinical trial information: NCT02684266 .
The incidence and impact of brain metastasis in patients with hereditary BRCA1/2 mutated invasive breast cancer in a prospectively followed cohort.
Authors: Garber Haven , Lehner Michael , Raghavendra Akshara Singareeka , Gutierrez-Barrera Angelica M. , Tripathy Debu , Litton Jennifer Keating , Arun Banu , Ibrahim Nuhad K.
Published: May 2020

1096

Background: Previous reports suggest the incidence of brain metastasis is higher in patients with hereditary BRCA1 mutations compared to BRCA1 noncarriers among breast cancer patients who develop recurrent disease. PARP inhibitors are now standard therapies for metastatic breast cancer patients with germline BRCA1 or BRCA2 mutations ( gBRCA1/2) based on their efficacy in treating systemic disease. However, as management of systemic disease improves, a concern is that patients with hereditary BRCA mutations may experience higher rates of disease progression in the CNS. We aimed to estimate the incidence of brain metastasis in breast cancer patients with gBRCA1/2 using a prospectively maintained gBRCA database and to assess the impact of brain metastasis on survival. Methods: To determine incidence, we queried a prospectively maintained electronic database that included patients referred to the MDACC genetics department and who underwent gBRCA1/2 testing. We identified patients with stage I-III invasive breast cancer who were treated between 2000-2017 and assessed for disease recurrence and brain metastasis. To expand our cohort for descriptive characteristics (separate from the incidence analysis), we queried the Breast Medical Oncology database for patients with brain metastasis who had undergone BRCA1/2 testing outside the genetics department or at outside institutions. Results: Of 474 patients with Stage I-III breast cancer and gBRCA1, 77 (16.2%) developed distant metastasis (median f/u: 9.1 years). Of these patients, 34/77 (44.2%) developed brain metastasis. In comparison, 42 of 318 (13.2%) of gBRCA2 patients with Stage I-III breast cancer developed distant recurrence (median f/u: 8.4 years), and 7/42 (16.7%) experienced brain metastasis. In gBRCA1 patients with brain metastasis, 45/48 (83.8%) had triple negative disease, and the median time from diagnosis to brain metastasis was 2.45 years. The brain was among the initial sites of disease recurrence in 24/48 (50%) of gBRCA1 patients. For gBRCA1 patients with distantly recurrent disease, median OS from diagnosis was 3.19 years for patients with brain metastasis vs. 5.37 years for patients without brain mets (HR 0.54; 95% CI 0.34 to 0.85; P = 0.0082). Conclusions: Brain metastasis is frequent among breast cancer patients with recurrent disease and hereditary BRCA1 mutations. Development and testing of agents with intracranial activity is critical for improving long-term outcomes in gBRCA1 patients with metastatic breast cancer.
Caring for transgender cancer patients: Shortcomings of medical education.
Authors: Gil Deza Ernesto , Abal Mariana , Gil Deza Lourdes , Garcia Gerardi Carlos , Martin Reinas Gaston , Tognelli Flavio , Gercovich Daniela , Gonzalez Cesar , Jaunarena María del Huerto , Lovisolo Rubén , Navigante Alfredo , Montiel Monica , Nunell Marcelo Andres , Smolje Leonel , Fernandez Mariano G , Kaminski Estefania E , Muino Marcelo , Danussi Inés , Morgenfeld Eduardo L. , Gercovich Felipe G. ,   USAL-HM ECOE 2019
Published: May 2020

11002

Background: Caring for transgender patients requires specific knowledge and skills. Medical schools spend less than 5 hours on average training for treatment of LGBT patients (Obedin-Maliver, JAMA, 306 (9), 971). This paper assesses the knowledge on the topic and skills of postgraduate Oncology students from Universidad del Salvador at the Observational Standard Clinical Examination (OSCE) 2019 (JCO 34 (15), Abstract e18150, 2017). Methods: At one of the stations of OSCE 2019, students had thirty minutes to complete a clinical record of a simulated transman patient with ovarian cancer stage IIIC. Based on the real case of Robert Eads, actors were trained with the documentary on his life “Southern Comfort”. Students were assessed on: A) knowledge of the transman condition, B) use of preferred gender pronoun by the patient, C) discontinuation of testosterone treatment, D) recommendation of genetic study, E) treatment of ovarian cancer according to NCCN guidelines, F) moral discomfort with LGBT patient care. All interviews were filmed or recorded by an observer. All films, recordings and clinical records were reviewed to rate the students' performance. Results: A total of 25 postgraduate Oncology students took the OSCE 2019. Assessment: A) 5/25 (20%) lacked knowledge of the transman condition, B) 3/25 (12%) did not use the patient's preferred gender pronoun, C) 17/25 (68%) discontinued testosterone, D) 23/25 (92%) requested genetic study, E) all students treated ovarian cancer according to NCCN guidelines, F) none expressed moral discomfort with LGBT patient care. Conclusions: 1) It is feasible to assess the knowledge and skills required for treatment of transgender patients in Oncology. 2) We found shortcomings of student's medical training regarding transgender patients: one in five did not understand the patient's condition, three did not use the patient´s preferred gender pronoun during the interview and more than half suspended the necessary hormone therapy for their condition. 3) This emphasizes the need to deepen our medical and communication skills in order to assist the transgender population and should be included in future ASCO-ASH milestones for specialty accreditation.
Effect of video-based patient education on pancreatic cancer knowledge and behavior.
Authors: Turell Wendy , Ackbarali Tariqa , O'Reilly Eileen Mary , Alsante Matthew , Pucci Kathryn , Del Nido Elizabeth A
Published: May 2020

11005

Background: Treatment outcomes for pancreatic cancer are optimized when patients/caregivers are engaged, informed and supported participants in their care. However, challenges exist regarding care engagement, disease and treatment related education, and the attainment of adequate psychosocial support. To address these needs, we created video-based patient education activities with the National Pancreas Foundation to empower patients/care with information and resources on pancreatic cancer facts, diagnosis, medical management, and strategies to minimize side effects and maximize quality of life. Methods: One 1-hour patient education activity was broadcast live and online, followed by on-demand release, in 2018-2019 at CancerCoachLive.com and via Facebook Video for 12 months. Features included panel discussions, slides, live polling and Q&A, and video vignettes of real patient experiences. Knowledge-focused test questions were administered at 3 time points (pre-activity, immediate post-activity, and 2-mos [follow-up] post). Behavioral and communication-focused questions were also asked at follow-up. Data from these questions, live poll responses, and learner-submitted questions pre-event and during live Q&A were analyzed to determine engagement, lessons learned and continuing patient needs. Results: In total, 6,276 patients took part in the activity. Patient questions prior to and during the activity focused on basic knowledge about pancreas gland function, tumor development, disease escalation, and medical management. In-session polling results revealed that prognosis and life expectancy were the top concerns for participants. Two months post-education evaluation showed: 33% reported improved communication with their healthcare providers (HCPs) regarding pancreatic cancer; 46% reported improved feelings of being more “in-control” of health care decisions; 25% reported improved care behaviors for their health. Reports of improved HCP communication were specific to: side effect management, clinical trials availability, treatment option knowledge, and confidence related to engaging in discussions. Knowledge improvements were observed for 3 of 4 questions related to facts about the pancreas, pancreatic cancer, and treatment.Conclusions: Patient/caregiver education on pancreatic cancer yields gains in knowledge and behavior, improves patient/caregiver engagement, improves treatment decision-making, and maximizes quality of life.
Enhancing cancer literacy among Appalachian Kentucky middle and high school students.
Authors: Hudson Lauren , Prichard Chris , Weiss L. Todd , Vanderford Nathan
Published: May 2020

11008

Background: Kentucky has the highest rates of overall cancer incidence and mortality in the United States and the Appalachian region of the state experiences the highest burden of the disease. Poor health behaviors, poverty, poor health care access, low education levels, and low health literacy drive the cancer disparities in Kentucky. Inadequate health literacy is associated with lower participation in preventive measures, which can increase one’s risk of developing cancer. Increasing cancer literacy among youth represents an opportunity to potentially decrease cancer disparities across Kentucky. In a recent study, we piloted a cancer education intervention in Kentucky middle and high schools to determine if such an intervention could enhance students’ cancer literacy. Through the study, we documented a significant increase in students’ short-term cancer literacy levels (Hudson L. et al. Journal of Cancer Education, in press). Methods: This quantitative survey research study aims to examine the long-term effects of the cancer education intervention on the cancer literacy of Kentucky middle and high school students. An online pretest cancer literacy survey consisting of 10 items was administered to a new set of 164 participants from six new schools, followed by the delivery of a cancer education presentation. Immediately following the presentation, participants took a posttest with identical items to the pretest. A follow-up identical test is being administered 3 months after the initial intervention to determine participants’ longer-term knowledge retention. Results: Replicating our prior work, significant (p < 0.0001) increases in both average and median percent of correctly marked items (average: pretest = 50% versus posttest = 77%; median: pretest = 50% versus posttest = 80%) and scores on each individual question were observed immediately following the intervention. Additionally, the average rating as to how the intervention influenced students considerations toward encouraging a family member or friend to change their habits following the intervention was 8 (1 = extremely unlikely;10 = extremely likely). Conclusions: This work demonstrates an increase in cancer literacy levels after the educational intervention and indicates that the information motivates participants to share cancer prevention information with others. A follow-up survey will measure participants’ longer term knowledge retention levels. These data may suggest that a school-based educational intervention can change behaviors that can lower cancer incidence and mortality rates.
Gender variation in clinical activity and Medicare payments among medical oncologists and hematologists.
Authors: Konda Manojna , Roy Arya , Parikh Richa , Fugere Tyler , Gullapalli Manoja , Pandey Yadav , Verma Rashmi
Published: May 2020

11014

Background: While physician sex has been shown to impact salary even after adjusting for productivity, gender-based differences in clinical activity and reimbursement for oncologists and hematologists are not completely understood. We evaluated the differences in Medicare reimbursement for male and female physicians in medical oncology and hematology. Methods: A retrospective analysis using Centers for Medicare & Medicaid Services Physician and Other Supplier Public Use File (POSPUF) for the year 2017 was performed to identify charges and total payment information for individual oncologists and hematologists. Mean values were compared using two-sample t-test, and the medians were compared by Wilcoxon rank-sum test. Results: A total of 8553 oncologists and hematologists (2710 women and 5843 men) were included in the POSPUF in 2017. Female physicians submitted a mean of 16,754 fewer charges (95% CI, −19,696 to −13,812; P < .0001), collected a mean of $173,632 less in revenue (95% CI, −201,184 to −146,080; P < .0001), and submitted a mean of 5.65 fewer unique billing codes (95% CI, - 6.69 to - 4.61; P <.0001) compared to their male counterparts. Women represented 219 of the 1069 most highly productive oncologists and hematologists (20.4%) and collected a mean of $281,263 (95% CI, −417,517 to −145,008; P < .0001) less than similarly productive men. Conclusions: This study suggests that female oncologists and hematologists submit fewer Medicare charges and receive lower Medicare payments compared to male providers. Even among similarly productive hematologists and oncologists, women collected less revenue than men. Further research is required to explore causes for this difference. [Table: see text]
Is burn-out-syndrome a problem among oncology workers? Incidence and effective tools to achieve improvement.
Authors: Cunquero Tomas Alberto Jacobo , Ortega Inmaculada , Gomez Ana , Lobo De Mena Miriam , Ramirez Belloch María del Rocío , Gil Raga Mireia , Iranzo Vega , Fernandez Diaz Amaya Belen , Shaheen Ihsan , Meri Abad Marina , Núñez Abad Martin , Franco de la Rosa Milagros , Aparisi Francisco , Safont Aguilera Maria Jose , Godes Maria Jose , Berrocal Alfonso , Caballero Cristina , Blasco Ana , Camps Carlos
Published: May 2020

11016

Background: Burn-Out Syndrome (BOS) is defined by (1) emotional and physical exhaustion; (2) cynicism and depersonalization; and (3) no personal nor professional fulfillment. It affects up to 78% of oncology-related workers (doctors, nurses and nurse-assistants, among others). This may decrease quality in both patient assistance and institutional processes. However, there is lack of resources for its diagnosis and management. Our objective is to: (1) determine the incidence of BOS in our team; (2) analyze potential causes; and (3) decrease in 20% the percentage of BOS affected workers. Methods: From October 2018 to November 2019, 20 nurses and nurse-assistants participated. Process map and Ishikawa fish-bone diagram were design to analyze BOS potential causes and to design appropriate interventions after Priority/pay-off matrix description. To do so, participants were asked to fulfill a personal detail questionnaire at the beginning, and adapted versions for the GHQ-12 and Maslach Index questionnaires after each intervention. To track the improvement process, a PDSA cycle was fulfilled and re-evaluated overtime. Project developed through the ASCO Quality Training Program and the Fundación ECO support. Results: Population main characteristics: 87% women, 47-year-old median age. 12 nurses, 6 working in the clinic. 90% with more than 5 years of experience in Oncology. At baseline, 75% healthy (GHQ-12), BOS cause risk: exhaustion 70%, depersonalization 45%, fulfillment 55%. Two interventions developed to improve exhaustion BOS risk: (1) ergonomy tips; and (2) self-assessment and self-help tools. 9 subjects lost after 2nd intervention. After interventions, 34% exhaustion risk reduction and 100% healthy workers (GHQ-12). Conclusions: After two interventions, we have achieved an improvement of 34% lowering the risk of suffering BOS among our workers. Health perception improved to 100%. The loss of 9 subjects after the 2nd intervention may be a bias when interpreting the final results. Giving the appropriate tools to medical oncology workers helps reduce BOS risk significantly
The experience of first-year hematology and oncology fellows after implementing a wellness chief fellow at an academic cancer center.
Authors: Rogers Sherise C. , Walker Alison R. , Otterson Gregory Alan , Dettorre Janet
Published: May 2020

11017

Background: Hematology & Oncology trainees are high risk for burnout. Risk factors include early stage in career, female gender and isolation. From previous assessment, the program discovered that the feeling of isolation was a problem experienced by our trainees. Our first-year fellows are challenged with multiple acclimations and the intense demands of inpatient service. As a result, we developed the leadership position of Wellness Chief Fellow to address the specific needs of this population during academic year 2019. Methods: The Wellness Chief (WC) is a third-year Hematology and Oncology Fellow with good communication skills and knowledge of resources at the academic cancer center. The WC gave a Wellness lecture during first-year orientation to emphasize the prioritization of personal wellbeing throughout fellowship. The WC developed a list of wellness resources within the hospital system and local community and shared these with the fellows. The WC also provided quarterly one-on-one confidential mentoring to first year fellows. These meetings were informal and semi-structured. Topics included adjusting to the academic center and their new fellowship role, moving to a new city, current support system, clinical and research mentorship, life challenges and self-care. Mid-year, the first-year fellows were surveyed regarding their experience. Results: Eight fellows participated in one-on-one mentoring and 5 completed a mid-year evaluation. 4/5 fellows were new to the city. All trainees felt that mentoring helped them adjust to fellowship. 4/5 stated that they found a clinical mentor and 3/5 have a research mentor and started a research project. 4/5 acknowledged that they have a friend in the fellowship program and 5/5 stated that they do have someone to go to if they were experiencing a challenging life event. All fellows reported gaining something valuable after each mentoring session. 3/5 subjectively experienced burnout within 6 months of the fellowship program. One person stated they experienced burnout once per week and 2 reported monthly burnout. Conclusions: A Wellness Chief Fellow can buffer the effects of isolation within the first-year fellowship experience by providing mentoring and resources during a challenging acclimation period.
Optimizing management of glioblastoma: Educational impact on clinicians.
Authors: Worst Michelle Arielle , Carothers Ann , Parikh Kinjal , Brauer Lisa , Lombardi Giuseppe , Cloughesy Timothy Francis
Published: May 2020

11026

Background: Glioblastoma multiforme (GBM) is a rare, malignant tumor of the central nervous system (CNS) with poor prognosis. Nearly all patients experience recurrence due to GBM’s heterogeneity and there is currently no standard approach to treatment. Despite having few targeted agents with demonstrated efficacy, molecular testing is utilized due to its value in improving diagnostic accuracy and prognostic stratification. Moreover, recent data has shown an increase in promising data with regards to treating GBM using various mechanisms. Because of the clinical conundrum GBM poses and the lack of available treatment options, clinicians are challenged to stay current with new data and how best to integrate new agents into treatment paradigms. The objective of this study was to assess the changes in oncologists’ and pathologists’ knowledge through participation in education regarding optimal GBM treatment. Methods: The educational activity was a 30-minute online, video discussion segmented into 3 parts with synchronized slides and 2 faculty. Educational effect was assessed with a repeated pairs pre-/post-assessment study with a 3-item, multiple choice, knowledge questionnaire and one confidence assessment question. For all questions, each participant served as his/her own control. Pre- and post-assessment scores were compared to determine the relative changes in the proportion of correct responses. A chi-square test assessed statistical significance at the P < 0.05 level. The activity launched 26th June 2019; data were collected until 19th August 2019. Results: Overall significant improvements were seen after education for oncologists (N = 62, P < .001) and pathologists (N = 67, P < .01). The relative improvement was 67% for oncologists and 45% for pathologists (pre-/post-assessment average correct response rates were 30%/50% and 29%/42%, respectively). Following the activity, 55% of oncologists and 51% of pathologists had a measurable improvement in confidence in their ability to differentiate among late-stage investigational agents for GBM based on mechanism of action. Conclusions: Participation in an online, CME intervention consisting of a series of video discussions, totaling 30-minutes, resulted in statistically significant improvements in knowledge and confidence of oncologists and pathologists, that may lead to improvements in clinical care. As new data and agents emerge, new educational activities are necessary to reinforce knowledge, close persistent gaps, and increase oncologists’ and pathologists’ confidence in this clinical setting.
Lung cancer screening knowledge in four internal medicine university programs.
Authors: Urrutia Argueta Samuel , Basnet Nishraj , Brittan Mollie , Abdul-Kafi Owais , Hanna Nasser H.
Published: May 2020

11027

Background: Low density CT (LDCT) screening reduces lung cancer specific and all-cause mortality in high risk populations. However, it remains underutilized. Screening discussions often start in primary care clinics of which nearly 30% are occupied by residents. Recognizing gaps in knowledge in early medical training may translate into a higher utilization of LDCT screening. Methods: To evaluate knowledge about lung cancer screening in Internal Medicine (IM) residents at 4 academic programs we distributed a survey to assess population at risk, mortality benefits, comparison between LDCT, colonoscopy and mammogram, and a knowledge self assessment. Results: 166 out of 360 (46%) IM residents at the 4 institutions participated, including 42% PGY-1, 30% PGY-2, and 28% PGY-3. Residents attained an average of 2.9 correct responses out of 7 (43.1%), without any statistically significant difference among programs. PGY-1 residents performed better than PGY-2 and PGY-3 (p=0.022). 36% correctly identified the appropriate population for screening. 90% correctly indicated that LDCT screening results in a cancer specific mortality reduction. 59% correctly indicated that LDCT results in all-cause mortality reduction. 7.7% answered that women stand to benefit the most from screening. 66% correctly answered that LDCT underperforms colonoscopy regarding mortality reduction. 22% answered correctly that LDCT outperforms mammography in reducing mortality. 65% of residents perceived their knowledge to be average or lower. Conclusions: LDCT knowledge is deficient among the residents studied. PGY-1 residents performed significantly better than their upper level peers. There were no significant differences among institutions. [Table: see text]