bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC).
Authors: Ghatalia Pooja , Handorf Elizabeth A. , Deng Mengying , Zibelman Matthew R. , Abbosh Philip , Anari Fern , Greenberg Richard E. , Viterbo Rosalia , Chen David , Smaldone Marc C. , Kutikov Alexander , Geynisman Daniel M. , Uzzo Robert Guy
Published: June 2021

4582

Background: The role of CN in mRCC was challenged by the results of the CARMENA trial in the targeted therapy (TT) era. We sought to evaluate the role of both upfront and deferred CN in pts receiving modern IO-based and TT regimens. Methods: Pts with synchronous mRCC who received systemic therapy (tx) for mRCC after 2011 were included from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic tx alone, systemic-> CN, and CN-> systemic tx. Overall survival (OS) was calculated from the time of initiation of first therapy – systemic or CN. Patient characteristics were compared using chi-squared tests or t-test. Weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regressions with time-varying covariates were used to assess the effect of tx on survival. Adjustment was conducted via inverse probability of treatment weighing based on the generalized propensity score, estimated via Bayesian Additive Regression Trees. Covariates in the model were age, gender, race, insurance at mRCC diagnosis, and IMDC risk group. Results: Of 1719 pts with mRCC, 972 (56.5%) received systemic tx alone, 605 (35.1%) received CN-> systemic tx, and 142 (8.2%) received systemic->CN. 310 pts received IO or IO/IO, 123 pts received IO+TT and 1152 pts received only TT. The median follow-up was 37.1 months. In adjusted analyses using propensity score weighting and time-varying covariates, CN-> systemic was significantly associated with improved OS compared with systemic tx alone (Table). When stratifying groups by type of systemic treatment (IO and TT), there was improvement of OS in the CN groups compared to systemic tx alone, although we lacked power to reach statistical significance. Among CN-treated patients, the order of systemic tx relative to CN did not change OS (hazard ratio [HR] = 1.00, 95% CI 0.76-1.32, p=0.96). Conclusions: Using a national, EHR-based cohort, which includes a large number of IO treated pts, our findings support an oncologic role for CN in select mRCC pts. The timing of CN, for pts who were able to receive both systemic therapy and CN, may not affect overall outcome. The associated improvement in survival of CN is seen in pts receiving IO and TKI based systemic tx.[Table: see text]
Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).
Authors: Labaki Chris , Alaiwi Sarah Abou , Schmidt Andrew Lachlan , El Zarif Talal , Bakouny Ziad , Nuzzo Pier Vitale , Xu Wenxin , Braun David A. , McGregor Bradley Alexander , Choueiri Toni K.
Published: June 2021

4583

Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated with worse outcomes in RCC patients receiving ICIs. Methods: This study evaluated a retrospective cohort of patients with RCC at Dana-Farber Cancer Institute in Boston, MA. Clinical information including demographics, IMDC risk score, RCC histology, steroid administration, ICI regimen, line of therapy, time to treatment failure (TTF) and overall survival (OS) were collected. Patients were divided into those receiving HDC (prednisone ≥10 mg or equivalent for ≥ 1 week, HDC group) or not receiving HDC (No-HDC group). HDC administration was evaluated in relation to TTF and OS in a univariate analysis (Log-rank test) and a multivariate analysis (Cox regression). Results: 190 patients with RCC receiving ICIs were included, with a median age of 59 years. HDC were administered to 56 patients and 134 patients received no (N= 116) or only low-dose (N=18) steroids. In the HDC group, 40 patients received steroids for immune-related adverse events, 8 for other cancer-related indications, and 8 for non-oncological indications. There was no difference in TTF between the HDC and No-HDC groups (12-mo TTF rate: 34.8 vs. 32.3%, respectively; log-rank p=0.65). Similarly, there was no difference in OS between the HDC and No-HDC groups (36-mo OS rate: 56.7 vs. 62.4%, respectively; log-rank p=0.97). After adjusting for IMDC risk group, RCC histology, ICI regimen type, and line of therapy, TTF and OS did not differ in the HDC group as compared to No-HDC group (HR=1.14 [95%CI: 0.80-1.62], p=0.44 and HR=1.17 [95%CI: 0.65-2.11], p=0.59, respectively). Conclusions: In this retrospective study of patients with RCC treated with ICIs, administration of high-dose corticosteroids was not associated with worse outcomes.[Table: see text]
Adjuvant chemotherapy with CAV/IE for malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): An institutional analysis from Indiana University.
Authors: Wei Cynthia , Cary Clint , Masterson Timothy A. , Foster Richard , Ashkar Ryan , Adra Nabil , Hanna Nasser H. , Einhorn Lawrence H.
Published: June 2021

5026

Background: Malignant transformation of teratoma to PNET has an aggressive disease biology and generally poor outcomes when metastasis occurs. The optimal management of patients (pts) with PNET who have complete surgical extirpation is unknown. Most pts who are monitored with surveillance will relapse. We report results from pts with metastatic PNET who had complete surgical resection to NED status followed by adjuvant chemotherapy, most commonly cyclophosphamide + doxorubicin + vincristine alternating with ifosfamide + etoposide (CAV/IE) for 4 cycles. Methods: We reviewed records for pts with histologically confirmed malignant transformation of teratoma at Indiana University from 1990 to 2020. We identified 13 pts with PNET who underwent resection of metastatic disease to NED status followed by treatment with adjuvant chemotherapy, most commonly CAV/IE comprising of cyclophosphamide (1200 mg/m2), doxorubicin (75 mg/m2), and vincristine (2 mg/m2) alternating with ifosfamide (1.8 g/m2) plus etoposide (100 mg/m2). Treatment was delivered every 3 weeks for 4 cycles or until unacceptable toxicity. Results: Thirteen pts with metastatic PNET resected to NED status and received adjuvant chemotherapy were identified. Median age at diagnosis was 29 (range, 20 to 55). Primary tumor site was testis in 11 pts, retroperitoneum in 1 pt, and mediastinum in 1 pt. Metastasis site was retroperitoneal lymph nodes in 11 pts, mediastinal lymph nodes in 1 pt, and local mediastinal recurrence in 1 pt. After resection to NED status, all 13 pts were treated with adjuvant chemotherapy: 11 pts were treated with CAV/IE and 2 received etoposide-ifosfamide-cisplatin (VIP) x 2. Among the 11 pts who received CAV/IE: 3 pts received < 4 cycles due to toxicity and 8 completed 4 cycles. With a median follow-up of 16.3 months, 3 of 13 pts relapsed (23%) and 10 of 13 remained continuously disease free (77%). Of those who relapsed, median time to relapse was 9.3 months, 2 remained alive with disease at follow up and one patient died of disease progression. Conclusions: Adjuvant CAV/IE improves the outcomes of pts with malignant transformation of teratoma to PNET and who had resection of metastasis to NED status. Most pts who received adjuvant therapy remain continuously disease-free in comparison to historically high relapse rates in pts with resected PNET monitored with surveillance.
Efficacy of TIP (paclitaxel, ifosfamide and cisplatin) as salvage chemotherapy for relapsed germ cell cancer patients stratified by the modified International Prognostic Factors Study Group (IPFSG) score: The Northern Ireland (NI) Experience.
Authors: Uprichard Adam , Scott Julie-Anne , Mcaleer James , Carser Judith , Oladipo Olabode
Published: June 2021

5028

Background: Salvage therapy for relapsed or refractory germ cell tumours (GCTs) after first-line treatment (1LT) failure remain controversial. The ongoing TIGER trial aims to compare conventional-dose chemotherapy (CDCT) using TIP with high-dose chemotherapy (HDCT) and to validate a modified version of the IPFSG stratification system as a secondary objective. We retrospectively analysed data from patients treated with TIP at our institution and stratified by the modified IPFSG (mIPFSG) groupings, correlating this with clinical outcomes. Methods: Data from all GCT patients who received TIP in NI between 2005 and 2014 was collected. Patients were scored using known IPFSG factors including progression-free interval (0-1), metastasis site (0-3), response to 1LT (0-2), primary tumour site (0-3), HCG (0-1), AFP (0-2), and histology (-1 to 0), and categorised into the modified strata. Descriptive and inferential statistics using SPSS compared survival measure outcomes and the favourable response rate (FRR) i.e the proportion of patients achieving either a complete response or partial response with normal serum tumour markers, according to mIPFSG group. Results: Thirty patients were identified, all of whom received 4 cycles of TIP. The median age was 37 years (range 17-57), 28 patients were non-seminoma histology with 2 patients seminoma. The cohort comprised predominantly of patients with more adverse mIPFSG features and the FRR of the group was 30%, with a median progression-free survival (PFS) of 9 months and 2-year overall survival (OS) of 50%. Clinical outcomes differed by mIPFSG score as shown below. Conclusions: Our study shows TIP efficacy comparable to published data, and to our knowledge is the first to show correlation between clinical outcomes with the regimen and the new mIPFSG model. The differences in outcomes to CDCT using TIP across risk groups in real world practice shows potential for a stratified approach to patient selection for salvage therapy, as is under investigation by the TIGER study.[Table: see text]
A methodology for the extraction and analysis of real-world radiographic and electronic medical record data to reconstruct treatment arms of historical prostate cancer clinical trials.
Authors: Lindsay William David , Ahern Christopher A. , Kamauu Aaron , Wilder Robert , Chagin Karen , Taps Timmothy
Published: June 2021

5033

Background: Real-world evidence (RWE), including synthetic comparator arms created from historical real-world data (RWD), has the potential to support the safety and efficacy evaluation of new medical products. However, many available RWD sources lack the details necessary to reliably identify patients comparable to clinical trial cohorts or to assess essential oncologic efficacy endpoints. This project demonstrates the ability to extract and analyze RWD to identify patients matching eligibility criteria to four historical clinical trials in metastatic castration-resistant prostate cancer (mCRPC), and calculate outcome measures. Methods: A total of 5,741 patients treated for prostate cancer at multiple institutions (2010-2020) were analyzed in two cohorts using data extracted from the EMR, Tumor Registry, Oncology Information System, and Picture Archiving and Communication System. Of 3,486 patients with prostate cancer in Cohort 1, 422 mCRPC patients were identified: those treated with ADT who achieved castration-level testosterone ( < 50 ng/dL), had evidence of metastatic disease, and exhibited rising PSA (PCWG2). These patients were further matched to four historical clinical trial treatment arms (COU-AA-301: 49, COU-AA-302: 143, AFFIRM: 30, PREVAIL: 79), based on prior chemotherapy and receipt of Abiraterone or Enzalutamide. Overall survival (OS) and time to skeletal related events (SRE) (pathological fracture, spinal compression, surgery to bone, and radiotherapy to bone) were calculated based on diagnosis and procedure codes using the Kaplan-Meier (KM) Estimator. Of 2,255 patients with prostate cancer in Cohort 2, 101 patients received Abiraterone or Enzalutamide and 59 patients had sufficient baseline and follow-up imaging to be scored. Radiographic progression-free survival (rPFS) was calculated from the start of treatment to the time of progression (RECIST 1.1) or loss to follow-up using the KM estimator. Results: In Cohort 1, median OS was 37.7 months (95% CI: 31.5-NR), and median time to SRE was 17.9 months (13.5-22.6). Median OS per patient cohort matched to historical trial treatment arm was COU-AA-301: 23.7 months (10.7-NR), COU-AA-302: 45.9 months (34.9-NR), AFFIRM: 35.3 months (6.34-NR), PREVAIL: 41.5 months (21.9-NR). In Cohort 2, median rPFS was 37.2 months (13.3-NR). Conclusions: The methodology employed in this analysis not only successfully identified a cohort of RWD patients similar to clinical trial-defined patients, but also curated sufficiently reliable data to calculate essential endpoints (e.g., rPFS). At scale, this methodology can be used to generate RWE, including synthetic comparator arms to support clinical trials with radiographic endpoints.
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.
Symptom identification and management in epithelial ovarian cancer.
Authors: Hickman Ashley , Ruddy Kathryn Jean , Pachman Deirdre R. , Fischer Kristin , Rahman Parvez , Goergen Krista M. , Lee Minji , Cheville Andrea L. , Wahner Hendrickson Andrea Elisabeth
Published: June 2021

5554

Background: A better understanding regarding the burden of treatment side effects in patients with gynecological malignancies could help guide symptom interventions and oncologic therapy decision-making. We aim to inform understanding of symptom burden in epithelial ovarian cancer (EOC) by analyzing patient-reported symptom data from patients treated for this condition over a 16-month period. Methods: Patients receiving medical oncology care at Mayo Clinic Rochester and at Midwest Mayo Clinic Health System community sites have received symptom-focused surveys prior to each medical oncology visit since March 28, 2019 through the Enhanced Electronic Health Record Facilitated Cancer Symptom Control Study (E2C2). These surveys, administered either through the electronic medical record portal or on a clinic tablet prior to each oncology office visit, no more frequently than every 2 weeks, include six linear analogue scales measuring sleep disturbance, pain, anxiety, emotional distress, and fatigue (SPADE), as well as physical dysfunction on a scale of 0 (none) to 10 (as bad as you can imagine). Scores of 0-3 were considered mild symptoms, 4-6 moderate symptoms, and 7-10 severe symptoms. We collected survey results from March 28, 2019 to July 20, 2020 for patients with EOC and reviewed the number of surveys per patient in addition to the average symptom scores. Results: From March 2019 to July 2020, for patients with EOC, there were 2974 encounter-based surveys from 762 patients. The number of surveys completed by each patient ranged from 1-20. The following number of patients returned the correlating number of surveys: 1 survey:240 patients; 2 surveys:145; 3 surveys:79; 4 surveys:56; 5 surveys:58; 6 surveys:45; 7 surveys:38; 8 surveys:27; 9 surveys:22; ≥10 surveys:52. The average score from all surveys for each symptom was: 2.41 for sleep disturbance, 2.03 for pain, 2.32 for anxiety, 1.97 for emotional distress, 3.26 for fatigue, and 2.50 for physical dysfunction. Please see the table for the proportion of surveys that reported symptoms as mild, moderate, or severe. Conclusions: Fatigue and physical dysfunction were reported most frequently in patients with EOC, while emotional distress and pain were reported least frequently. 20% of surveys reported moderate to severe emotional distress, while 40% reported moderate to severe fatigue. A targeted approach to symptom management is needed for patients undergoing EOC evaluation and treatment. Our next steps in this analysis include an assessment of potential predictors of greater symptom burden (e.g., specific treatments, age, and other clinical and sociodemographic characteristics). Clinical trial information: NCT03892967. [Table: see text]
Real-life data of niraparib maintenance treatment in patients with recurrent platinum-sensitive ovarian cancer.
Authors: Vilming Bente , Fallås-Dahl Jørgen , Bentzen Anne-Gry , Ingebrigtsen Vibeke Anett , Berge Nilsen Elisabeth , Vistad Ingvild , Dørum Anne , Solheim Olesya , Bjørge Line , Aune Guro , Lindemann Kristina
Published: June 2021

5560

Background: PARP (poly adenosine diphosphate [ADP]–ribose polymerase) inhibitors are the new standard for maintenance treatment in platinum sensitive recurrent ovarian cancer (PSROC), independent of germline (g-BRCA) or somatic BRCA mutation status. Real-life data after the introduction of new anti-neoplastic agents are needed to evaluate whether the benefit observed in phase III trials can be translated into clinical practice. The aim of this study was to provide real-life data on efficacy and safety of niraparib in non-gBRCA PSROC. Methods: This retrospective multi-center cohort study included patients with PSROC who were enrolled in a national individual patient access program in Norway. Efficacy and safety data were collected from the patients´ electronic medical records. The primary outcome was time from start of niraparib treatment to first subsequent treatment (TFST). Secondary endpoints included prevalence of dose interruption and -reduction, as well as adverse events. Results: The study included 106 patients with median age of 64 years (range 38-81). After median follow up of 15.3 months (95% CI 12.1-18.5), 71 patients (67%) had progressed, 64 (60%) had started a new line of treatment, and 25 (24%) had died. 25 (24%) patients were still receiving niraparib. Median duration of niraparib treatment was 7.6 months (0.4 to 27.3 months). Median TFST was 11.7 months (95% CI 9.2 -14.2). Patients with elevated CA125 after chemotherapy prior to start of niraparib had shorter progression-free survival (PFS) compared to patients with complete serological response (6.5 months (95% CI 5.7 – 7.3) vs 12 months (95% CI 6.2 – 17.9, (p < 0.001)). Grade 3-4 hematologic and non-hematologic events occurred in 25% and 17% of the patients, respectively. The most common grade 3/4 hematologic events were anemia (15%), thrombocytopenia (11%) and neutropenia (8%). Adverse events led to dose interruption in 38% and dose reduction in 44% of the patients. Patients with individualized dosing based on baseline weight and platelet counts had fewer dose reductions (p < 0.001) and -interruptions (p = 0.042) than patients whose dose was not adjusted to those baseline values. Conclusions: In a real-life setting, niraparib maintenance treatment in patients with non-gBRCA PSROC showed efficacy comparable with the published phase III data and an acceptable safety profile. Individualized dosing at start of treatment minimized adverse events. The prolonged PFS in patients with CA125 normalization after last chemotherapy, suggests that these patients in particular benefit from maintenance treatment but warrants confirmation in a larger sample.[Table: see text]
Anlotinib plus sintilimab in patients with recurrent advanced endometrial cancer: A prospective open-label, single-arm, phase II clinical trial.
Authors: Wei Wei , Ban Xiaohua , Yang Fan , Huang Yongwen , Li Jibin , Qiu Ya , Cheng Xiaqin , Li Jundong , Zheng Min
Published: June 2021

5583

Background: Endometrial cancer is one of the most common gynecologic malignancies in the world. however, the effects of systemic chemotherapy are limited. The combination of targeted therapy with immunotherapy is a new research field in the treatment of malignant tumors. Anlotinib is a novel tyrosine kinase inhibitor with highly selective inhibition effects on multi-targets, especially on vascular endothelial growth factor receptor, Platelet-derived growth factor receptor and Fibroblast growth factor receptor. Sintilimab is a highly selective, fully humanized, monoclonal antibody, which blocks the interaction between Programmed death 1 and its ligands. This research aimed to evaluate the efficacy and safety of the combination of anotinib and sintilimab in patients with recurrent advanced endometrial cancer. Methods: Patients who received at least one platinum-based systemic chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1 were considered eligible for enrollment. Sintilimab was administered intravenously (200mg，q3w); anlotinib was taken orally (12mg qd, d1-14, 21 days per cycle). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included duration of response, disease control rate (DCR), progression-free survival (PFS), overall survival and safety. Results: From November 2019 to to September 2020, 23 patients with a median age of 56 years (range: 37-70), FIGO stage IA (21.7%), IB (8.7%), II (4.4%), IIIA (13.1%)，IIIC (30.4%), IVB (21.7%) were enrolled. Among these participants, 22 patients were evaluable. The therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 13.6%, 63.7%, 13.6% and 9.1% respectively, yielding the ORR of 77.3% (95%CI: 58.3%-96.3%) and the DCR of 91.7% (95%CI: 79.8%-100%). ≥1 and ＜1 Combined Positive Score of PD-L1 expression were observed in 66.7% (14/21) and 33.3% (7/21) patients respectively, and the ORR was 92.9% (95%CI: 77.4%-100%) and 57.1% (95%CI: 18.4%-90.1%) in the two groups. The median time of the first response was 1.5 months (range, 0.7-12.8). The median PFS was not reached. Most of the occurring adverse events (AEs) were grade 1 or 2. Grade 3 AEs included ileus (4.3%), immune myocarditis (4.3%) immune peritonitis (4.3%), hand-foot syndrome (8.7%), neutropenia (4.3%), neutrophils decrease (4.3%), and hypertension (4.3%); Grade 4 AE was lymphocytosis (4.3%). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: Anlotinib plus sintilimab showed a promising antitumor activity with a favorable toxicity profile for patients with recurrent advanced endometrial cancer. We will report more data in the future. Clinical trial information: NCT04157491.
Metabolic and bariatric surgery among endometrial cancer survivors: Are we missing an opportunity to help?
Authors: Gray Justin , Myneni Ajay A , Towle-Miller Lorin M , Simmonds Iman , Burnstein Matthew , Schwaitzberg Steven , Hoffman Aaron B , Zsiros Emese , Noyes Katia
Published: June 2021

5591

Background: Multiple studies have delineated a clear link between the estrogenic effects of obesity and the incidence of endometrial cancer (EC). Obese EC patients are less likely to receive guideline-recommended surgical treatment (ST) relying instead on chemotherapy and radiation therapy. Furthermore, EC patients are more likely to die from obesity-related complications than from cancer-related causes. Several small-scale studies have demonstrated that metabolic and bariatric surgery (MBS) could offer EC patients fast, safe and effective weight loss, which provides an opportunity to improve survival. This is the first population-based study that examines uptake and outcomes of MBS among EC survivors in New York State (NYS). Methods: This study was based on the all-payer longitudinal data from the NYS’s Statewide Planning and Research Cooperative System and included inpatient and ambulatory surgeries performed between 2006 and 2012. Using ICD and CPT diagnostic and procedure codes, we identified patients diagnosed with EC for the first time, and we further examined whether they received ST within one year of their initial EC diagnosis. We followed EC patients with ST for 4 years to examine the rates of MBS, and we assessed long-term patient outcomes through 2019. We conducted bivariate and multivariate analyses to evaluate all-cause mortality and identify risk factors for poor surgical outcomes and readmissions. Results: Among 24,950 EC patients (2006-2012), 16,156 (65%) of them underwent ST within 1 year of EC diagnosis. Compared to those who did not receive ST, patients who underwent ST were younger, less likely to be White and more likely to be from urban counties, had private insurance, diagnosed with diabetes and hypertension, and had lower Elixhauser scores for readmission and mortality ( p < 0.01 for all). Within 4 years following ST, 136 (0.8%) EC patients underwent MBS. Those who underwent MBS were younger ( p < 0.01), predominantly white, privately insured, morbidly obese ( p < 0.01) and diabetic ( p = 0.01) compared to those who did not undergo MBS. Conclusions: Despite having higher risk of mortality from obesity-related complications such as diabetes and cardiovascular disease, the proportion of EC patients obtaining MBS (0.8%) was similar to that seen among the US population eligible for MBS (1.0%). More research is needed to understand barriers to MBS among eligible women with EC.