bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world first-line (1L) treatment patterns in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a U.S. health insurance database.
Authors: Swami Umang , Hong Agnes , El-Chaar Nader N. , Nimke David , Ramaswamy Krishnan , Bell Elizabeth J. , Sandin Rickard , Agarwal Neeraj 
Published: June 2021

5072 Background: Over the past 6 years, intensification of androgen deprivation therapy (ADT) with docetaxel (DOC) and novel hormonal therapies (NHT) [abiraterone, enzalutamide, and apalutamide], has been shown to improve survival outcomes in men with mCSPC. This study assessed the real-world utilization of effective combination therapies as 1L treatment in insured pts in the U.S. with mCSPC. Methods: This retrospective study used the Optum health insurance claims database, which includes pt claims data from both commercially insured and Medicare Advantage populations. Eligible pts were adult men with ≥1 claim with a metastatic International Classification of Diseases diagnostic code (first claim was index date) within 90 days (d) prior to, or any time after, a prostate cancer diagnosis between January 2014 and June 2019. Pts with evidence of systemic anticancer therapy during the 1-year pre-index baseline period were excluded, unless the first drug claim occurred within 90 d prior to the diagnosis of metastatic disease. The 1L treatments were identified as any treatment for mCSPC within 90 d pre-index, plus any other treatment received within 180 d of the first, and were grouped by regimen: ADT only; ADT + first-generation antiandrogens (AA); ADT + DOC; ADT + NHT; and ADT + NHT + DOC. Results: Of 4221 men with mCSPC, 2364 (56.0%) received ADT only; 892 (21.1%) ADT + AA; 577 (13.7%) ADT + NHT; 348 (8.2%) ADT + DOC; and 40 (0.9%) ADT + NHT + DOC. Pts who received ADT + DOC or ADT + DOC + NHT were generally younger than the other treatment groups (Table). By 2019, use of ADT only and ADT + AA had declined, while the use of ADT + NHT and ADT + NHT + DOC had increased (Table). However, in 2018 and 2019, the majority of men with mCSPC still received either ADT alone, or ADT + AA, including those with visceral metastases (Table). Survival analysis across treatment cohorts is ongoing. Conclusions: Despite level 1 evidence demonstrating improved survival with intensified treatment (ADT + DOC or NHT), this study shows its underutilization in pts with mCSPC. This is evident even in those with more aggressive disease (visceral metastases) as recently as 2019. These data highlight that a minority of pts with mCSPC received optimal life-prolonging therapies in a commercially insured and Medicare Advantage U.S. population. Further studies are needed to identify the reasons for this underutilization of intensified treatments.[Table: see text]
Real-world treatment patterns among patients diagnosed with metastatic castration-sensitive prostate cancer (mCSPC) in community oncology settings.
Authors: George Daniel J. , Agarwal Neeraj , Rider Jennifer R , Li Benjamin , Shirali Rohan , Sandin Rickard , Hong Agnes , Russell Dave , Ramaswamy Krishnan , Freedland Stephen J. 
Published: June 2021

5074 Background: Androgen deprivation therapy (ADT) served as standard of care for mCSPC for decades. Combining ADT with docetaxel (DOC) starting in 2015 or with novel hormonal therapies (NHT) starting in 2017 has demonstrated improved survival compared to ADT alone. This study examined the impact of new evidence on treatment selection for mCSPC patients in real-world oncology practice. Methods: Electronic medical record (EMR) data from a network of U.S.-based oncology practices in the ConcertAI Oncology Dataset were used to retrospectively evaluate treatment patterns in mCSPC patients who initiated first-line (1L) therapy between 2014–2019. We estimated the proportion of mCSPC patients receiving each 1L regimen, duration of therapy until initiation of next regimen, and trends in 1L regimen. Treatment patterns were studied in the overall population and by race/ethnicity. Anti-androgen (AA) use for <90 days was not included. Results: A total of 858 mCSPC patients were included (70% White, 16% Black, 3% Hispanic, and 11% other race/unknown). Median age at mCSPC diagnosis was 69 years, and 63% presented with de novo metastases. The most common mCSPC 1L regimens were ADT + older AA (26.3%, mainly bicalutamide), ADT monotherapy (20.5%), ADT + NHT ± AA (19.2%), and ADT + DOC ± AA (16.4%). The remaining 17.5% received a variety of other therapies, including AA monotherapy (5.9%) or NHT ± AA (5.5%). NHT included abiraterone, apalutamide, and enzalutamide. ADT + NHT ± AA treatment increased each year, while ADT + DOC ± AA treatment peaked in 2017 and then decreased (Table). By contrast, ADT + AA was the most common therapy in 2014 but declined every year. Median duration until initiation of a subsequent regimen was 14.3 months for ADT + NHT ± AA and 10.8 months for ADT + DOC ± AA. Differences in 1L treatment patterns across White and Black patients were not statistically significant in unadjusted analyses. Conclusions: Even in 2019, over half of mCSPC patients treated in real-world settings did not receive 1L therapy now known to significantly improve survival (ADT + NHT or ADT + DOC) over ADT alone. Those who did, received shorter durations of treatment than observed in registrational trials. However, we found no initial evidence of racial disparities in treatment. The disconnect between trial evidence and real-world practice could be due to patient/disease characteristics, cost/access issues, or provider awareness. A better understanding of these contributing factors is worthy of further study.[Table: see text]
The prognostic performance of PREDICT+ in patients (pts) with HER2-positive (HER2+) early-stage breast cancer (EBC).
Authors: Agostinetto Elisa , Ameye Lieveke , Martel Samuel , Aftimos Philippe Georges , Ponde Noam , Maurer Christian , El-Abed Sarra , Wang Yingbo , Vicente Maria Lourdes , Chumsri Saranya , Bliss Judith , Kroep Judith R. , Colleoni Marco , Petrelli Fausto , Del Mastro Lucia , Moreno-Aspitia Alvaro , Piccart-Gebhart Martine J. , Paesmans Marianne , de Azambuja Evandro , Lambertini Matteo 
Published: June 2021

524 Background: PREDICT+ is a widely used, free, online tool based on traditional clinico-pathological features, including HER2, developed to predict individual mortality of EBC pts and to aid clinical decision making for adjuvant therapy. However, its prognostic role in HER2+ EBC pts treated with chemotherapy (CT) and anti-HER2 therapies remains unclear. We aimed to investigate the prognostic performance of PREDICT+ in HER2+ EBC pts enrolled in the ALTTO trial. Methods: ALTTO is a phase III study evaluating adjuvant lapatinib (L) +/- trastuzumab (T) vs. T alone in pts with HER2+ EBC. Pts enrolled in the ALTTO trial and receiving T-based therapy started concurrently with CT were eligible for this analysis. We calculated PREDICT+ estimates using variables extracted from ALTTO database, blinded to pts outcomes. The prognostic performance of PREDICT+ was evaluated by assessing its calibration and discriminatory accuracy. For calibration, median predicted 5-year (5-yr) overall survival (OS) was compared to observed 5-yr OS. For discriminatory accuracy, the area under the receiver-operator characteristic (AUC under the ROC) curve and corresponding 95% confidence intervals (CI) for predicted 5-yr OS were calculated. Subgroup analyses were performed according to type of anti-HER2 therapy, type of CT, age, hormone receptor (HR) status, nodal status and tumor size. Results: This analysis included 2,794 pts. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT+ underestimated 5-yr OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups (Table). For discriminatory accuracy, AUC under the ROC curve was 73.7% (95%CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analysed subgroups. Conclusions: In HER2+ EBC pts enrolled in the ALTTO trial, the PREDICT+ score highly underestimated OS. The low performance of this prognostic tool was consistent across all pts subgroups. PREDICT+ should be used with caution to give prognostic estimation in HER2+ EBC pts treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.[Table: see text]
Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer: Final analysis.
Authors: O'Malley David M. , Oaknin Ana , Matulonis Ursula A. , Mantia-Smaldone Gina , Lim Peter C , Castro Cesar Martin , Provencher Diane M. , Memarzadeh Sanaz , Zweidler-McKay Patrick A. , Wang Jiuzhou , Esteves Brooke , Moore Kathleen N. , Gilbert Lucy 
Published: June 2021

5504 Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of MIRV with bevacizumab (BEV) was evaluated in pts with FRα-positive (medium/high expression; ≥50%/ ≥75% of cells with PS2+ staining intensity), platinum agnostic ovarian cancer, defined as pts with either platinum resistant (PROC) (recurrence within 6 months after last platinum dose) or platinum sensitive (PSOC)responded to the last platinum therapy and did not progress within 6 months) for whom a non-platinum based doublet would be appropriate. Methods: Pts received MIRV (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed by investigator according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 60 pts received the combination, with a median age of 60 years, a median of 2 prior lines of systemic therapy (range 1-4) and a median follow-up of 17.5 months. The cohort included 32 pts (53%) with PROC disease and 28 (47%) with PSOC disease. Objective responses were seen in 28 of 60 pts for a confirmed overall response rate (ORR) of 47% (95% CI, 34, 60), median duration of response (mDOR) of 9.7 months (95% CI 6.7, 12.9), and median progression free survival (mPFS) of 8.3 months (95% CI 5.6, 10.6). In pts with high FRα expression (n=33), the confirmed ORR was 64% (95% CI 45, 80), mDOR of 11.8 months (95% CI 6.7, 13.7), and mPFS of 10.6 months (95% CI 8.3, 13.3); efficacy results in PROC and PSOC subsets of pts with high FRα expression are shown in the table below. The most common treatment related AEs (all grade, grade 3+) were diarrhea (68%, 2%), blurred vision (63%, 2%), fatigue (58%, 7%), and nausea (57%, 0%). The most common treatment related grade 3 and 4 AEs were neutropenia and hypertension, (12%, 3% and 13%, 0%, respectively); all other grade 3+ events occurred in ≤ 10% of pts. Conclusions: The combination of MIRV with BEV demonstrates impressive anti-tumor activity with durable responses and favorable tolerability in high FRα recurrent ovarian cancer. These results build on data previously reported for MIRV/BEV in PROC patients ( Gyn Oncology O’Malley, et al 2020), suggesting that MIRV has the potential to be a preferred partner for BEV in patients with high FRα recurrent ovarian cancer regardless of platinum sensitivity. Clinical trial information: NCT02606305. [Table: see text]
An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer (KGOG 3045, AMBITION).
Authors: LEE JUNG-YUN , Kim Byoung-Gie , Kim Jae-Weon , Lee Jung Bok , Park Eunhyang , Kim Sung Hoon , Choi Chel Hun , Kim Hee Seung 
Published: June 2021

5520 Background: Heavily treated platinum-resistant ovarian cancer remains a therapeutic challenge. Although standard therapy includes non-platinum single agent chemotherapy (CT), prognoses are very poor in this setting. Anticancer therapies based on molecular biomarkers have improved dramatically. We report data from an umbrella study of biomarker-driven targeted therapy (olaparib, O; cediranib, C; durvalumab, D; tremelimumab, T) in platinum-resistant recurrent ovarian cancer (NCT03699449). Methods: Patients with platinum-resistant ovarian cancer with ≥ two lines of prior chemotherapy and ECOG 0/1 were eligible for this study. In the screening phase, archival tumor samples were tested for HRD and PD-L1 status. Treatment arms were allocated according to the test results. For HRD+ patients, we tested the synergistic effects of O with other agents: patients were randomly allocated to arm 1, O+C (O 200mg bid + C 30mg qd); or arm 2, O+D (O 300mg bid + D 1500mg q4w). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression: arm 3, D+CT (D 1500mg q4w + PLD or topotecan or weekly paclitaxel [6 cycles]) in patients with high PD-L1 expression; arm 4, D+T75+CT (D 1500mg q4w + T 75mg q4w [4 doses] + PLD or topotecan or weekly paclitaxel [4 cycles]) in patients with low PD-L1 expression; or arm 5, D+T300+CT (D 1500mg q4w + T 300mg [1 dose] + weekly paclitaxel [60mg/m2 D1,8,15 q4w for 4 cycles]) in patients with low PD-L1 expression. Recruitment to arm 5 was initiated after completion in arm 4. The primary endpoint was objective response rates (ORR) according to RECIST 1.1. Results: Between Dec 2018 and Oct 2020, 70 patients were allocated to treatment as follows: arm 1 (n = 16), arm 2 (n = 14), arm 3 (n = 5), arm 4 (n = 18), and arm 5 (n = 17). Median age was 57 years (range 34-77) and median prior lines of treatment was 3 (range: 2-10). Among all patients, the ORR was 35.7% (25/70, 95% CI: 24.6%-48.0%); complete response was observed in two patients. The ORRs (95% CI) for each treatment arm were shown (Table). Treatment-related grade 3/4 adverse events were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients in each treatment arm, respectively. No treatment-related adverse events (TRAEs) leading to discontinuation of treatment and no grade 5 TRAEs were observed. Conclusions: This is the first biomarker-driven umbrella study conducted in patients with platinum-resistant recurrent ovarian cancer. This umbrella study provides preliminary evidence on the clinical benefit of biomarker-driven targeted therapy. All regimens were manageable, without unexpected toxicities. Clinical trial information: NCT03699449. [Table: see text]
Underutilization of germline BRCA testing in commercially-insured women diagnosed with ovarian cancer.
Authors: Cham Stephanie , Wright Alexi A. 
Published: June 2021

5539 Background: Germline BRCA (gBRCA) testing has prognostic, therapeutic, and familial implications for patients with ovarian cancer. Since 2010, national guidelines have recommended universal genetic testing, but few data are available about rates and timeliness of testing or factors associated with testing. Methods: We examined rates of gBRCA testing and the time from index procedure to testing among commercially-insured women aged 18 to 64 with claims for ovarian, fallopian tube, or primary peritoneal cancers cancer who received cytoreductive surgery and chemotherapy between 2008-2018. We used logistic regression to assess patient-, clinician-, and practice-level characteristics associated with testing. Results: Overall, the rate of g BRCA testing was 33.9%, increasing from 14.7% in 2008 to 46.4% in 2018; the median time to testing decreased from 280.0 to 72.5 days. Patients who were tested were younger than those who were not (mean [SD] 54.7 [9.9] years vs. 58.1 [11.8] years, P<.001) and had fewer comorbidities (Charlson score ≥2: 3.7% vs. 9.5%, P=0.01). There were no differences in testing rates by US region, rurality of practice location, or medical vs. gynecologic oncology providers. However, testing rates were higher in academic and NCI-designated cancer centers (36.2% and 32.5%, respectively), compared with community practices (25.5%; P<0.001) (Table). In adjusted analyses, lower test rates were associated with older age (aOR=0.97, 95%CI=0.96-0.98), more medical comorbidities (Charlson score ≥2: aOR=0.77, 95%CI=0.61-0.97), and community practices vs. NCI cancer centers (aOR=0.64, 95%CI=0.46-0.88). Conclusions: While the rates and time to testing for gBRCA in patients with new diagnoses of ovarian cancer have improved over time, testing remains underutilized, even among well-insured populations. Future studies should examine barriers to timely genetic testing and identify scalable strategies for increasing testing in women with ovarian cancer, particularly for women treated in community practices.[Table: see text]
Serum-based assay for adnexal mass risk of ovarian malignancy.
Authors: Ure Daniel , Bullock Rowan , Altwerger Gary , Ratner Elena , Northrop Lesley 
Published: June 2021

5551 Background: A Deep learning neural network was developed to assess ovarian cancer risk in women presenting with adnexal mass into risk categories. The algorithm shows potential to improve on the performance of CA-125 as the standard biomarker to monitor women as a clinical management metric to trace increased risk of malignancy. Methods: Serum specimens from an enriched biobank (N = 2688) were collected during previous clinical studies from women presenting with an adnexal mass at risk of ovarian cancer. Protein biomarker data from these specimens were used to develop a novel neural network for binary stratification of ovarian cancer risk assessment. These specimens were divided between training and testing data sets using 5-fold cross validation during training. A randomized, separate sample set was withheld from use in training and testing the algorithm for independent validation purposes. As algorithm inputs seven biomarkers are used in the network: cancer antigen 125, human epididymis protein, beta-2 microglobulin, apolipoprotein A-1, transferrin, transthyretin, and follicle stimulating hormone. In addition to these biomarkers, the patient’s age and menopausal status are used. Menopause was defined as the absence of menses for ≥12 months. The algorithm uses supervised learning with known histopathology diagnoses as the labels for training. The algorithm is a classification deep feedforward neural network. The neural network is regularized using node dropout to reduce overfitting. The final layer of the neural network has two nodes and uses the softmax function to assign a binary classification of low or high-risk of malignancy. Results: Algorithm performance metrics are also shown comparing predicted results from the algorithm to the known malignancy diagnoses. The performance metrics are also compared below to the standard of care biomarker test, cancer antigen 125 (CA125), reporting increased sensitivity by 26.1%, and failure to reject the null hypothesis of equivalent specificity. Conclusions: The algorithm detected 91% of malignancies in the independent validation data. This high sensitivity in malignancy detection paired with the failure to reject the null hypothesis of equivalent specificity (Pearson’s chi-squared test p-value of 0.281) and negative predictive value (NPV) suggest the algorithm could be used two-fold. First, surgical referral to gynecological oncologists for women classified in the high-risk cohort. The second as a goal with future clinical validation, is that women with a low risk of malignancy might be able to delay surgery and enter into a serial monitoring clinical management care pathway.[Table: see text]
Disparities in ovarian cancer treatment and overall survival according to race: An update.
Authors: Huffman Deanna , Jayakrishnan Thejus Thayyil , Shankar Karthik , Peterson Chelsea , Wegner Rodney E. 
Published: June 2021

5552 Background: It has long been identified that black women with ovarian cancer have worse overall survival when compared to white women. Disparities in the adherence to NCCN guideline-directed treatment and socioeconomic characteristics may be responsible for the differences in these outcomes. Methods: A retrospective review of National Cancer Database (NCDB) was performed to identify patients diagnosed with ovarian cancer from 2012-2016. We defined adherence to NCCN (National Comprehensive Cancer Network) guidelines as having stage and year-appropriate chemotherapy and surgery. Differences in guideline adherence, socioeconomic characteristics and survival outcomes were assessed. Results: In total, 32,163 were identified meeting the study criteria; 27,744 identified their race as “white” and 2,204 identified their race as “black”. Characteristics associated with higher likelihood of black race were advanced stage of disease- stage III (OR = 1.1869, CI = 1.03-1.37) or stage IV disease (OR = 1.4495, CI = 1.23-1.70) and treatment in a comprehensive (OR = 1.5757, CI = 1.16-2.15) or academic (OR = 2.3023, CI = 1.70-3.12) treatment facility. Variables associated with a lower likelihood of black race were higher education level (OR for high school degree < 6.5 % = 0.2501, CI = 0.21-0.30) and higher median household income (OR for income > $63,333 = 0.4218, CI = 0.36-0.49). Whether the care received was adherent to NCCN guidelines did not seem to be associated with black race (OR for adherence = 1.0021, CI = 0.89-1.13). 5-year overall survival for patients who received adherent care was 58% for white patients vs. 49% for black patients. Among those who didn’t receive adherent care, the outcomes were 49% among white patients vs. 38% among black patients. Conclusions: Overall survival remains worse for black patients, regardless of whether their care adhered to NCCN guidelines as defined by our study. This suggests that while receipt of care that is not adherent to NCCN guidelines seems to be negatively associated with overall survival, we must consider and evaluate other socioeconomic, environmental and system factors that are contributing to this continued survival discrepancy in women being treated for ovarian cancer.