bluuebunny/crossref_metadata_2025 huggingface dataset:
Final survival results from a multicenter, randomized phase II trial of intravenous paclitaxel plus FOLFOX (ivPOF) and/or intraperitoneal paclitaxel plus FOLFOX (ipPOF) versus mFOLFOX6 as first-line treatment of advanced gastric cancer (AGC): SYLT/FNF 004.
Authors: Zhao Shen , Lin Rongbo , Fan Nan-Feng , Chen Yigui , Li Xiaofeng , Lin Peicheng , Chen Wujin , Fang Wenzheng , Zhu Jinfeng , Li Hui , Liu Jie
Published: June 2021

4041

Background: Progression-free (PFS) and overall (OS) survival for SYLT/FNF 004 were previously reported in ASCO and ASCO-GI 2019. At that time, PFS was statistically significantly improved with ivPOF or ipPOF compared to mFOLFOX6 as first-line treatment of AGC; however, there were no significant between-treatment differences in OS. Herein, we report final survival results for this trial. Methods: Subjects were randomly assigned to one of three treatments: intravenous paclitaxel 135 mg/m2 + mFOLFOX6 omitting the 5-FU bolus (ivPOF); intraperitoneal paclitaxel 80 mg/m2 + mFOLFOX6 omitting the 5-FU bolus (ipPOF); or mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 followed by 5-FU 400 mg/m2 bolus and 5-FU 2400 mg/m2 as a 46-hour continuous infusion). Treatment cycles were repeated every 14 days for up to 9 cycles. Thereafter, maintenance treatment with S-1 80 mg/m2/day for 14 days every 3 weeks until disease progression, unacceptable toxicity, patient refusal, or physician decision. The original study objective was to compare ivPOF or ipPOF vs. mFOLFOX6 for PFS. Due to slow accrual, the protocol was later amended to compare POF (ivPOF and ipPOF) with mFOLFOX6 for PFS. Results: Between Nov 2015 and May 2018, 89 subjects (30 ivPOF, 29 ipPOF, 30 mFOLFOX6) were enrolled. As of the data cutoff on Dec 31, 2020, median follow-up was 41 (IQR: 37-43) months. The median number of cycles administered was 7 (IQR: 4-9) for POF; 6 (IQR: 4-9) for ivPOF; 9 (IQR: 4-9) for ipPOF; and 4 (IQR: 3-9) for mFOLFOX6. Median PFS and OS, respectively, were 6.23 (95% CI: 4.90 to 9.07) and 10.17 (95% CI: 8.97 to 16.4) months for POF and 4.55 (95% CI: 2.73 to 6.87) and 6.87 (95% CI: 5.83 to 13.6) months for mFOLFOX6. Both PFS and OS were statistically significantly better with POF, ivPOF or ipPOF versus mFOLFOX6 (Table). Safety was consistent with previous reports. Conclusions: POF, ivPOF or ipPOF improved both PFS and OS compared with mFOLFOX6, with similarly manageable adverse effects. Clinical trial information: NCT02845908. [Table: see text]
Real-world outcomes of second-line ramucirumab plus paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma: A nationwide retrospective study in Korea (KCSG-ST19-16).
Authors: Zang Dae Young , Han Hye Sook , Kim Bum Jun , Jee Hee-Jung , Suh Young Ju , An Hyonggin , Byun Ji-Hye , Kim Dong Sook , Park Se Hoon , Rha Sun Young , Oh Do-Youn , Kim Jong Gwang , Bae Woo Kyun , Kim In-Ho , Sym Sun Jin , Oh So Yeon , Kim Hyeong Su , Lee Keun Wook , Ryu Min-Hee
Published: June 2021

4056

Background: Ramucirumab as monotherapy or in combination with paclitaxel is a second-line treatment option recommended for patients with locally advanced unresectable or metastatic gastroesophageal junction (GEJ) or gastric adenocarcinoma. However, real-world data of large samples focused on ramucirumab plus paclitaxel in gastric cancer are limited. We conducted a nationwide retrospective study to evaluate the efficacy, safety, and factors potentially associated with survival in patients with gastric or GEJ adenocarcinoma who received second-line ramucirumab plus paclitaxel in a real-world setting. Methods: The study population comprised all patients with gastric or GEJ cancer who received ramucirumab plus paclitaxel in South Korea between May 1, 2018, and December 31, 2018. We included patients with advanced gastric or GEJ adenocarcinoma and disease progression after first-line platinum and fluoropyrimidine-containing combination chemotherapy. Results: A total of 1,063 patients with advanced gastric or GEJ adenocarcinoma who received ramucirumab plus paclitaxel were included. The objective response rate and disease control rate were 15.1% and 57.7%, respectively; the median progression-free survival was 4.03 months (95% CI, 3.80–4.27), and the median overall survival was 10.3 months (95% CI, 9.33–10.73). The common treatment-related adverse events (TRAEs) at any grade were neutropenia (44.7%), anemia (41.8%), neuropathy (29.1%), fatigue (25.9%), and anorexia (25.0%). Grade 3 or higher TRAEs with incidences of ≥5% were neutropenia (35.1%) and anemia (10.5%). Adverse events of special interest were infrequent, including hypertension (2.1%) and proteinuria (3.0%). Based on multivariate analysis, overall survival was negatively associated with Eastern Cooperative Oncology Group performance status ≥2, weight loss in the previous 3 months ≥10%, GEJ of primary tumor, poor or unknown histology grade, number of metastatic sites ≥3, presence of peritoneal metastasis, no prior gastrectomy, and time to second-line since first-line treatment < 6 months. Conclusions: Our large-scale, nationwide, real-world data analysis of an unselected real-world population added evidence for the efficacy and safety of second-line ramucirumab plus paclitaxel in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Clinical trial information: NCT04192734.
Alternating gemcitabine/nab-paclitaxel (GA) and 5-FU/leucovorin/irinotecan (FOLFIRI) as first-line treatment for de novo metastatic pancreatic cancer (MPC): Safety and effect.
Authors: Schroeder Brett A. , Mandelson Margaret T. , Picozzi Vincent J.
Published: June 2021

4125

Background: Both gemcitabine and 5FU-based chemotherapy have demonstrated efficacy in MPC. Alternating regimens may 1) reduce toxicity 2) slow resistant cancer biology emergence and 3) provide a broader platform for addition of other therapeutic agents. Alternating GA and FOLFIRI in MPC has been previously reported as part of the SEENA -1 trial,our own institution, and elsewhere (Picozzi et.al. GI Cancer Symposium 2017, Picozzi et.al, ASCO 2018 Assenat et,al, ASCO 2018). An extension of our institutional observations are reported here. Methods: Pt eligibility required the following: 1) biopsy proven de novo MPC, 2) no prior evidence MPC on CT, 3) ECOG performance status ≤ 2, and 4) bi-dimensionally measurable disease. Treatment (Rx) entailed gemcitabine 1000mg/m2 and nab-paclitaxel 125mg/m2 1, (8), 15 alternating every 8 wks (2 cycles) with FOLFIRI using standard dosing. Patients were radiographically re-staged every 8 wks. Rx was continued up to 48 wks; Rx thereafter decided by pt/MD. Results: 108 pts met eligibility requirements from 10/2015 and 12/2020. Pt characteristics included median age 68 ( range 35-81), ECOG PS 0/≥1 54%/46%, # diseases sites 1/≥1 62%/38%, liver /non-liver 76%/24%, biliary obstruction yes/no 40%/60%, C 19.9 NL/ < 59XNL/ > 59X NL 12%/32%/56%; median Ca 19.9 4598 With median f/u of 19.7 mo, 17 pts remain on Rx < 48 wks, 35/91 (38%) completed 48 wks Rx, 56/91 (62%) pts progressed prior to 48 wks. Median # mos on Rx was 8.9. ≥ grade 3 heme toxicity included anemia 7%, neutropenia 9%, thrombocytopenia 5%. Neutrophil growth factors were not used in this pt cohort. ≥ 3 non-hem toxicity included neuropathy1%, nausea/vomiting 2%, mucositis 2%, diarrhea 1%. Disease control at 16 wks was 81% (35% PR/46% SD/16% PD, 95% CI 72-87%). Median OS was 13.7 mo (95% CI 10.9-18.7 mo). 6 /12/18/24 mo OS were 87%/55%/41%/ 20% respectively. Prognostic significance was seen with Rx > vs < 48 wks (21.1 vs 8.0 mo, p <.0001), and ECOG PS 0 vs. ≥1 ( 17.8 vs. 10.9 mo, p = 0.03) Age, # metastatic sites, liver involvement, biliary obstruction and magnitude of CA 19.9 elevation all failed to achieve prognostic significance at the p <.05 level. Conclusions: 1) Alternating GA/ FOLFIRI in MPC has a more favorable toxicity profile than standard regimens 2) Med OS appears superior to GA and competitive with FOLFIRINOX ; longer term (18/24 mo ) OS seemed particularly encouraging 3) ≥ 48 wks Rx and ECOG PS 0 were prognostically significant 4) Further investigation using this regimen including a) randomized comparisons, b) incorporation of molecular data and c) addition of additional agents seems indicated Updated survival data will be presented at the meeting
Fecal microbiome composition in pancreatic cancer cachexia and response to nutrition support.
Authors: Moshayedi Natalie , Yang Julianne , Lagishetty Venu , Jacobs Jonathan , Placencio-Hickok Veronica , Osipov Arsen , Hendifar Andrew Eugene , Gong Jun
Published: June 2021

4129

Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis with a 5-year survival rate of 10.0%. Previous studies in stool microbiome indicate that microbiome composition has been associated with therapy response and pathogenesis across multiple cancers, and PDAC patients (pts) with higher bacterial diversity have demonstrated greater long-term survival. The fecal microbiome has not previously been characterized for PDAC pts with cancer cachexia or associated interventions. The study addressed the changes in microbiome over the course of treatment and the association between baseline bacterial composition and outcome in PDAC pts with cachexia. Methods: Stool specimens were collected from the PNCX1 trial (NCT02400398), where all pts were given a semi-elemental diet—enzymatically hydrolyzed protein—with enteral tube feeding. Stool samples (n = 29) were collected at time points aligned with enteral feeding and chemotherapy cycles separated by 6 weeks (C1D1, C2D1, and C3D1) and analyzed using 16S v4 sequencing of the microbiome. Microbiome changes from C1D1 to C3D1, weight stability, and overall survival (OS) were measured alongside microbiome characterization. Results: Pts with a complete set of stool samples were analyzed (n = 6) for differences in microbiome composition across treatment cycles. C3D1 samples were significantly associated with both an increased population of Veillonella and Actinomyces and decreased Bacteroides and Butyricicoccus compared to C1D1. Baseline stool microbiome composition was also evaluated to predict weight stability throughout treatment. In patient stool samples (n = 8) at C1D1, greater abundance of Veillonella (p = 0.0006) and reduced Bifidobacterium (p = 2.62E-5) were linked to greater weight stability. Microbiome alpha-diversity was also characterized using Shannon and Chao1 indices, where stable weight was related to reduced species richness (Chao1, p = 0.0194) but not evenness (Shannon, p = 0.1716). C1D1 patient stool samples were then analyzed and compared to OS (n = 16). Although no significant differences in global microbiome composition were noted between OS < 180 days and OS > 180 days, Parasutterella, Tyzzerella, Phascolarctobacterium, and Lachnoclostridium were identified as more prevalent in OS > 180 days despite their relatively low abundance. Conclusions: We are among the first evaluate stool bacteria changes over treatment course in PDAC pts. While Veillonella was associated with weight stability in a cohort of advanced PDAC pts all receiving enteral feeding, several genera were found in abundance in pts with prolonged OS, though this needs further validation. The potential impact of the gut microbiome and enteral feeding on weight stability is provocative given that cachexia is a hallmark of PDAC and an effective strategy to mitigate this process would be transformative.
Treatment outcomes in renal cell carcinoma patients with metastases to the pancreas and other sites.
Authors: Duarte Cassandra , Beuselinck Benoit , Weise Nicole , Dizman Nazli , Collier Katharine , Li Haoran , Martinez Chanza Nieves , Elias Roy , Rose Tracy L , Brugarolas James , Agarwal Neeraj , Mortazavi Amir , Pal Sumanta K. , McKay Rana R. , Hu Junxiao , Lam Elaine Tat
Published: June 2021

4557

Background: Metastatic RCC (mRCC) involving the pancreas is distinct from RCC involving other metastatic sites and is characterized by an indolent clinical course, heightened angiogenesis, and an inflamed stroma (PMID: 32271170). We previously reported on outcomes of RCC patients (pts) with pancreatic oligometastasis (ASCO GU 2020). We now report on outcomes in pts with mRCC involving the pancreas in conjunction with other metastases (mets). Methods: We conducted a retrospective, multi-institutional study of mRCC pts with mets to the pancreas and other sites. Data on pt demographics, tumor characteristics, systemic therapy, and outcomes were collected. Pts were classified based on treatment category: immunotherapy (IO) or vascular endothelial growth factor/receptor inhibitors (VEGFI). Outcomes measured included objective response rates (ORR), time-on-treatment (TOT), and overall survival (OS). Results: The analysis included 229 pts from 9 institutions, diagnosed between 1985-2020. Of these, 211 (92%) had clear-cell histology; 131 (57%) had nephrectomy; 41 (18%) had local pancreas-directed therapy; 111 (48%) had synchronous presentation of disease in the pancreas and other sites at time of mets. IMDC risk was favorable in 33%, intermediate in 41%, poor in 11%, and unknown in 15% pts. Median lines of therapy was 2 (range 0-9). Of 219 pts who received first-line (1L) therapy, 151 (69%) had VEGFI therapy, 41 (19%) had IO, and 18 (8%) had VEGFI/IO combination (Table). The IO group included 21 pts on checkpoint inhibitor (CPI), 16 pts on HD-IL2, 4 pts on other IO. 1L ORR was 39.7% for VEGFI (95% CI 31.8-48.0) and 31.7% for IO (95% CI 18.1-48.1) and was not statistically significant (NS, OR 1.4, 95% CI 0.65-3.23, p = 0.371). Median TOT for 1L therapy was 11.6m for VEGFI and 6.5m for IO (p = 0.0106). With a median follow-up of 51.5m, the median OS (mOS) for all pts from time of metastatic disease was 7.7 years (y) (95% CI 6.3-10.3). The mOS for pts who received 1L VEGFI was 7.6y (95% CI 5.5-9.5) and was not reached (NR) for those who got 1L IO (95%CI 6.5-NR); this difference was significant with an unadjusted p-value of 0.029. The pair-wise comparison between mOS of the 1L CPI subgroup compared to that of the 1L VEGFI group was significant (p = 0.0148). Conclusions: Consistent with the literature, mRCC pts with involvement of the pancreas in this study have prolonged OS compared to historical OS for the standard mRCC population. Additionally, our findings suggest that the choice of first-line therapy may impact outcomes. Additional analyses will be presented.[Table: see text]
Association of baseline neutrophil-to-eosinophil ratio (NER) and neutrophil-to-lymphocyte ratio (NLR) with response to combination immunotherapy (IO) with ipilimumab plus nivolumab (ipi/nivo) in patients with metastatic renal cell carcinoma (mRCC).
Authors: Tucker Matthew D. , Brown Landon Carter , Kao Chester , Hirshman Nathan , Kinsey Emily Noelle , Chen Yu-Wei , Ancell Kristin Kathleen , Beckermann Katy , Davis Nancy B. , McAlister Renee , Schaffer Kerry , Armstrong Andrew J. , Harrison Michael Roger , George Daniel J. , Rathmell Wendy Kimryn , Rini Brian I. , Zhang Tian
Published: June 2021

4563

Background: Previous reports have shown that the baseline neutrophil-to-lymphocyte ratio (NLR) is associated with prognosis in patients with mRCC. However, NLR has not been shown to reliably predict for response to IO. Retrospective analyses in metastatic melanoma and mRCC have shown an association of eosinophilia with improved outcomes to single agent immunotherapy. We sought to evaluate and compare the baseline NLR and NER with response to ipi/nivo in patients with mRCC. Methods: A retrospective review of patients with mRCC treated at the Vanderbilt-Ingram Cancer Center or Duke Cancer Institute with ipi/nivo was performed. Patients with clear cell histology and a baseline complete blood count with differential were included. Patients previously treated with IO were excluded. Patients were separated into groups (above and below the median) based on baseline median NER and baseline median NLR. Analyses of progression free survival (PFS) and overall survival (OS) were conducted using the log rank test. The odds ratio (OR) for objective response rate (ORR) was analyzed using Fisher’s exact test. Results: 111 patients met inclusion criteria. The median age was 60, 77% of patients were male, 68% had prior nephrectomy, 74% were naïve to systemic therapy, and 84% were IMDC intermediate/poor risk. The median NER was 25.0 and median NLR was 3.4. Patients with < median baseline NER had significant improvement in PFS, OS, and ORR (see table). Patients with < median baseline NLR had significant improvement in OS but not in PFS or ORR. Conclusions: Baseline NER was associated with improved outcomes with ipi/nivo. While both NER and NLR were associated with improved OS, only NER was additionally associated with both improved PFS and ORR. With multiple first-line treatment options for mRCC, baseline NER may serve as an early non-invasive predictor for response to ipi/nivo.[Table: see text]
Association of increased intensity of prostate-specific antigen screening in younger African American men with improved prostate cancer outcomes.
Authors: Qiao Edmund , Kotha Nikhil V. , Nalawade Vinit , Qian Alexander , Voora Rohith S. , Nelson Tyler J. , Stewart Tyler F. , Parsons John Kellogg , Rose Brent S.
Published: June 2021

5004

Background: African-American (AA) men are substantially more likely to present with lethal prostate cancer (PCa) at younger ages than non-Hispanic White men. Despite this disparity, AA men are poorly represented in the prostate-specific antigen (PSA) screening studies on which evidence-based PCa screening guidelines are based. This limits proper PSA screening guidance for AA men, especially for those younger than 55. We examined associations of PSA screening intensity with disease severity at diagnosis and prostate cancer-specific mortality (PCSM) in AA men < 55 years of age. Methods: The earliest recommended age to begin discussion of PSA screening is 40 years. We identified AA men aged 40-55 years, diagnosed with PCa from 2004 to 2017 within the Veterans Health Administration. PSA screening was identified using procedural codes. Screening intensity was defined as percentage of years screened within the pre-diagnostic observation period. This included up to 5 years prior to diagnosis. Multivariable logistic regression assessed the influence of PSA screening intensity on metastatic disease at diagnosis. Lead-time correction using published screening-dependent lead times was performed. PCSM was evaluated using Fine-Gray regression and non-cancer death as a competing event. Additional analysis was performed stratifying PSA screening into ‘High’ and ‘Low’ groups centered on the mean. Results: The cohort included 4,654 AA men at a mean age of 51.8 years with mean PSA screening rate of 53.2%. The pre-diagnostic observation period ranged from 1 to 5 years (median = 5 years). Median follow-up was 7 years. At diagnosis, there was a higher prevalence of Gleason sum ≥ 8 (Grade Group ≥ 4) and metastatic disease in the ‘Low’ group compared with the ‘High’ group ([Gleason sum ≥ 8 (Grade Group ≥ 4)]: 18.6% vs. 14.4%, p < 0.01; Metastatic disease at diagnosis: 3.7% vs. 1.4%, p < 0.01). Increased PSA screening intensity was associated with significantly reduced odds of metastatic disease at diagnosis (odds ratio: 0.61, 95% confidence interval (CI) = [0.47-0.81], p < 0.01) and decreased risk of PCSM (sub-distribution hazard ratio: 0.75, 95% CI = [0.59-0.95], p = 0.02). Conclusions: In this large national cohort of AA men aged 40 to 55 years, PSA screening increased intensity was associated with decreased risk of lethal disease and metastases at time of diagnosis and decreased PCSM. These data support the hypothesis that PSA screening and early prostate cancer detection may improve outcomes in younger AA men.
Survival of veterans treated with enzalutamide and abiraterone in advanced prostate cancer.
Authors: Schoen Martin W. , Carson Kenneth Robert , Luo Suhong , Eisen Seth , Reimers Melissa Andrea , Drake Bettina F. , Bennett Charles L. , Knoche Eric Marshall , Yan Yan , Sanfilippo Kristen Marie
Published: June 2021

5032

Background: Abiraterone (AA) and enzalutamide (ENZ) are two second generation antiandrogens used to treat advanced prostate cancer, but no large head-to-head trials have been performed. These oral therapies are commonly used in older patients with medical comorbidities who are not candidates for chemotherapy or clinical trials and have different mechanisms of action, adverse events, and drug interactions. To understand survival of patients with prostate cancer, we studied United States veterans treated prior to approval of AA and ENZ for metastatic hormone sensitive prostate cancer when both drugs had approval for metastatic castration resistant prostate cancer. Methods: We identified patients treated with AA or ENZ between 9/10/2014 and 6/3/2017 in the Veterans Health Administration and followed them to April 2020. Age, Elixhauser comorbidity score, treatment with androgen deprivation therapy (ADT) and docetaxel were collected. Cox proportional hazards modeling was used to assess the association between first oral treatment (AA or ENZ) and overall survival, while adjusting for covariates. Results: Of 5895 patients, 2562 (43.5%) were initially treated with ENZ, 3333 (56.5%) with AA, and 3040 (51.6%) received only one of the two drugs during the study period. Patients initially treated with ENZ compared to AA were older (mean 75.9 vs. 75.0 years, p = 0.001), had higher mean comorbidity score (6.2 vs. 5.9, p < 0.001), and were less likely to receive both ENZ and AA (45.2% vs. 51.0%, p < 0.001) or docetaxel (24.1% vs. 28.4%, p < 0.001). Patients who received only AA or ENZ and never received docetaxel were older (mean 78.3 vs. 73.2 years, p < 0.001) with higher mean comorbidity scores (6.4 vs. 5.7, p < 0.001). In the entire cohort, initial treatment with ENZ was associated with longer median survival (24.1 vs. 22.2 months, p = 0.003). After adjusting for age and comorbidities, ENZ was associated with a decreased risk of death compared to AA (HR 0.87, 95% CI 0.82-0.92). In 3317 patients who received two or more therapies (ENZ, AA, docetaxel) there was no difference in median survival between initial treatment with ENZ or AA (28.0 vs. 27.9 months). In 2578 patients (43.7%) who never received docetaxel and either ENZ or AA only, median survival was longer in patients treated with ENZ (18.9 vs. 13.6 months, p < 0.001) and was associated with decreased mortality when adjusting for age and comorbidities (HR 0.73, 95% CI 0.67-0.80). Conclusions: In the overall cohort, initial treatment with ENZ was associated with increased survival compared to AA. Patients who received only ENZ or AA and never received docetaxel had the largest benefit from ENZ, a difference of 5.3 months median survival. Efforts should be made to improve therapy selection for patients with prostate cancer, especially older patients with comorbidities.
The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.
Authors: Cooperberg Matthew R. , Brendel Paul , Lee Daniel J. , Doraiswami Rahul , Rajasekar Hariesh , Makarov Danil V. , Meeks William , Fang Raymond , Roe Matthew T , Shelton Jeremy B.
Published: June 2021

5061

Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]
PSMA-PET/CT Registry for Recurrent Prostate Cancer (PREP): Initial findings from a single center.
Authors: Kapoor Anil , Zukotynski Katherine , Tajzler Camilla , Hoogenes Jen , Matsumoto Edward , Uy Michael , Bauman Glenn , Metser Ur , Finelli Antonio , Ding Maylynn , Shayegan Bobby
Published: June 2021

5064

Background: Several lesion-targeted therapies exist for locally recurrent or limited stage metastatic prostate cancer (PCa) post-radiotherapy (RT) and radical prostatectomy (RP). However, detection of disease sites is limited using conventional imaging (CI) including computed tomography (CT) and bone scan. Prostate specific membrane antigen (PSMA) targeting PET radiopharmaceuticals like [18F]DCFPyL may help detect disease not seen on CI. Our objective was to assess the ability of PSMA targeted PET/CT to detect sites of disease recurrence and impact on patient management. Methods: This multi-center prospective registry study included six Ontario centers. Eligible patients in 1 of 7 clinical cohorts (Table) were identified and approved by Cancer Care Ontario (CCO) to have restaging with PSMA targeted PET/CT. Referring physicians were asked to complete a form indicating whether a change in management strategy would occur based on the PET/CT results. At 6 months post-PET/CT, actual patient management will be confirmed via provincial registries. These interim results are from a single center. Results: 253 patients were enrolled and had a PSMA targeted PET/CT. At baseline, median age was 71 years (range 50-102 years) and median PSA was 2.7 ng/mL (range 0.04-134.0 ng/mL). The majority of patients (n=59; 23.3%) were in cohort 2 (biochemical failure post-RP). In patients with negative CI, PSMA targeted PET/CT detected disease sites in 68.5% (170/248), resulting in a change in management for 67.8% (137/202) overall and 72.1% and 64.3% post-RT and post-RP, respectively. Conclusions: PSMA targeted PET/CT detected occult lesions on CI in the majority of patients enrolled, leading to a high rate of change in management. Our institutional results are in keeping with preliminary results reported for the provincial cohort. Clinical trial information: NCT03718260. [Table: see text]
Single-lesion PSMA protein expression and response to Lu-177 PSMA therapy in patients with castration-resistant prostate cancer.
Authors: Stangl-Kremser Judith , Rasul Sazan , Tosoian Jeffrey J. , Salami Simpa , Zaslavsky Alexander , Udager Aaron M. , Mazal Peter , Kain Renate , Comperat Eva , Pozo Salido Carmen , Steinbach Christina , Hassler-Di Fratta Melanie , Kramer Gero , Shariat Shahrokh , Palapattu Ganesh S.
Published: June 2021

5065

Background: The recent introduction of Lu-177 PSMA for the treatment of castration-resistant prostate cancer (CRPC) has been met with much excitement. Initial reports of clinical response are promising, despite known inter- and intra-patient molecular heterogeneity. In this study, we examined the utility of PSMA protein expression in metastatic tumor tissues as a predictor of lesion-specific response to Lu-177 PSMA therapy in men with CRPC. Methods: Between 2015-2020, 19 patients with metastases at multiple sites underwent metastatic lesion biopsy, Ga-68 PSMA PET imaging, and subsequent treatment with three cycles of Lu-177 PSMA. A monoclonal anti-PSMA antibody (EPITOMICS (USA), 1:50) was used to semi-quantitatively assess PSMA protein expression in the biopsy specimen. The histoscore (range 0-300) was derived from intensity and extent of the immunohistochemistry staining and was determined by experienced genitourinary pathologists. Imaging evaluation was performed according to the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria. We assessed the association of the PSMA protein expression in metastatic tumor tissues and the lesion-specific response to Lu-177 PSMA therapy. Results: In 12 patients with biopsy specimens available for staining, PSMA expression correlated with enhancement (SUVmax) of the biopsy site on Ga-68 PSMA PET imaging (rs = 0.63). Of the nine patients with repeat imaging after Lu-177 PSMA therapy, five (55.6%) had a lesion-specific response at the site of biopsy. PSMA expression on immunohistochemistry was unable to accurately predict lesion-specific response in univariable analysis (p = 0.81, 95% CI 94.6-76.6). Among the five men with a lesion-specific response, three (60%) experienced overall progression based on PERCIST. There was no association between lesion-specific response and overall progression (p = 0.64). Conclusions: In patients with multiple metastases, PSMA protein expression from a single site biopsy was not predictive of site-specific Lu-177 PSMA response based on PERCIST. Additional studies are necessary to further interrogate the clinical consequence of PSMA expression heterogeneity in metastatic sites as well as the mechanisms underpinning resistance to Lu-177 PSMA in patients with CRPC.
De-escalation of five years adjuvant endocrine therapy duration in patients with ER-low positive (immunohistochemical 1% to 10%) early-stage breast cancer: A propensity-matched analysis from the prospectively maintained database.
Authors: Yu Keda , Cai Yuwen , Shao Zhiming
Published: June 2021

538

Background: There are limited data on endocrine therapy benefits for patients with estrogen receptor (ER)-low positive breast cancer (staining 1% to 10% of tumor nuclei by immunohistology). We aimed to compare the effect of short-term 2-3 years versus standard 5 years of adjuvant endocrine therapy on survival outcomes in patients with ER-low positive early breast cancer. Methods: We used data from the prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center for this propensity-matched analysis. Women with ER-low positive, operable, and unilateral early-stage invasive ductal breast cancer were enrolled in this study. Patients with advanced disease, having received neoadjuvant chemotherapy or ovarian function suppression, or with unknown duration or longer than 5 years of adjuvant endocrine therapy were excluded. Enrolled patients were divided into three groups: received no endocrine therapy; received 2-3 years of endocrine therapy; and received approximately 5 years of endocrine therapy. The primary endpoint was disease-free survival (DFS). Multivariate Cox regression analysis and propensity score matching were performed to minimize bias. Hazard ratios (HR) with 95% CIs were calculated. Results: From 2012 to 2017, 634 patients with ER-low positive breast cancer in the database met the inclusion criteria. At a median follow-up of 60 months (interquartile range, 46-74), the 5-year DFS of the whole cohort was 84.9%, with 77.6% for patients who received no endocrine therapy (N = 89), 83.7% for patients who received 2-3 years endocrine treatment (N = 185), and 87.5% for patients who received 5 years endocrine therapy (N = 360). When compared with those receiving no endocrine therapy, patients receiving 5 years treatment was associated with a significantly improved DFS (HR, 0.55; 95% CI 0.32-0.95; P = 0.03); however, there was no significant difference in DFS between patients receiving 2-3 years and 5 years endocrine therapy (HR, 0.79; 95% CI, 0.48-1.28; P = 0.33). In the multivariate Cox regression analysis of the propensity score-matched samples of 360 patients, the DFS was not significantly better for patients who received 5 years of endocrine therapy than 2-3 years treatment (HR, 0.74; 95% CI 0.41-1.34; P = 0.32). An exploratory analysis of re-biopsy of the recurrence lesions indicated more than half of relapsed disease displayed ER-negative, and less than 5% lesions were proved to be ER ≥10% positive. Conclusions: Our data did not support the necessity of 5 years duration of endocrine therapy for patients with ER-low positive breast cancer. Short-term 2-3 years duration might be an alternative option. Further translational research on identifying endocrine-sensitive cases within ER-low positive patients is needed.
Differentiated activity profile for the PD-1 inhibitor balstilimab.
Authors: Joyce Cailin , Chand Dhan , Duckless Benjamin , Hidalgo Manuel , Grossman Joseph Elan , Kaleta Remigiusz , O'Malley David M.
Published: June 2021

5529

Background: The development and clinical application of immune checkpoint inhibitors has transformed the therapeutic landscape for cancer treatment in recent years. Balstilimab (AGEN2034) is a fully human, monoclonal IgG4 antibody that binds with high affinity to programmed death 1 (PD-1), thus preventing the interaction between this receptor and its ligands programmed death ligand 1 and 2 (PD-L1, PD-L2). Emerging evidence suggests that balstilimab exhibits a differentiated activity profile compared to currently approved anti-PD-1 agents, including pembrolizumab and nivolumab. Methods: Balstilimab as monotherapy was evaluated in a large phase 2 study in patients (pts) with recurrent/metastatic cervical cancer who had relapsed after a platinum-based treatment regimen for advanced disease. Pts were dosed at 3 mg/kg once every 2 weeks for up to 24 months and antitumor activity was assessed using RECIST v1.1. The tumor cell killing activity of balstilimab was evaluated preclinically in a human co-culture system of (1) primary T cells engineered to recognize NY-ESO-1 and (2) NY-ESO-1+ cancer cell lines, including PD-L1 and/or PD-L2-deficient engineered lines. The co-culture system was maintained for ̃ two weeks to drive partial T cell exhaustion; a state where cytotoxicity is compromised but recoverable with PD-1 blockade. Cytotoxicity of these partially exhausted T cells was quantified against PD-L1/L2 double positive, single positive, or double negative cancer cells in the presence or absence of PD-(L)1 antibodies. Results: In the second-line treatment setting for pts with advanced cervical cancer, balstilimab showed a numerically higher objective response rate (ORR) in subjects with PD-L1+, squamous cell carcinoma (SCC) tumors (21%, 95% CI, 12.7-32.6%) than those reported for pembrolizumab. Unlike pembrolizumab, balstilimab showed activity in PD-L1(-) pts, and irrespective of tumor histology (ORR 7.9%, 95% CI, 2.7-20.8%). Despite lower overall PD-L1 positivity compared to SCC (41.7 v 72.9%), an ORR of 12.5% (95% CI, 5.9-24.7%) was observed in the subset of pts with a poorer prognosis, those with cervical adenocarcinoma. Concordant with clinical observations, balstilimab demonstrated superior rescue of antigen-specific T cell cytotoxicity in vitro relative to pembrolizumab, nivolumab, or atezolizumab. Balstilimab also induced cytotoxicity against PD-L1 and/or PD-L2 deficient target cancer cells. Conclusions: Taken together, these data suggest functional differentiation of balstilimab from other PD-1 inhibitors with potentially important implications for extending the therapeutic reach of anti-PD-1 therapy. Investigation of the underlying mechanistic basis for these findings is ongoing. Clinical trial information: NCT03104699.
Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.
Authors: Poveda Andres , Lheureux Stephanie , Colombo Nicoletta , Cibula David , Lindemann Kristina , Weberpals Johanne I , Bjurberg Maria , Oaknin Ana , Sikorska Magdalena , Gonzalez Martin Antonio , Madry Radoslaw , Rubio María Jesus , Ledermann Jonathan A. , Davidson Richard , Blakeley Christopher , Bennett James , Brown Jessica , Skof Erik
Published: June 2021

5545

Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841. [Table: see text]
Does time to completion of radiation treatment in locally advanced vulvar cancer impact survival?
Authors: Nguyen Nancy T. , Zhao Xiao , Ponzini Matthew , Wilson Machelle , Leiserowitz Gary S. , Brooks Rebecca A.
Published: June 2021

5593

Background: Although well established in cervical cancer, it is unclear whether time from initiation to completion of radiation therapy for vulvar cancer affects survival outcomes. We seek to assess if completion of radiation, either alone (RT) or as concurrent chemoradiation (CRT), within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS). Methods: Women 18 years or older with FIGO stage II to IVA vulvar cancer who received external beam RT or CRT as part of their initial treatment course were identified from the National Cancer Database from 2004-2017. Patients with non-squamous cell carcinoma histology or who received systemic cytotoxic therapies as primary treatment were excluded. Patients who received less than 20 fractions of radiation were also excluded. Time to radiation completion was the number of days from the initiation to completion of radiation. The delay of radiation completion was calculated as the difference between the actual time to radiation completion and predicted duration of radiation. Types of treatment (RT and CRT) were both stratified into groups based on the delay of radiation completion, less than 7 days or greater than 7 days. Chi-square, Fisher Exact ANOVA and Kruskal-Wallis tests were used for analysis. Kaplan-Meier curves with log-rank tests were fit for univariate time-to-event analysis. Multivariable Cox proportional hazard models were fit to assess effects after controlling for confounding. Results: There were 2378 patients identified for analysis (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78) and the CRT group was younger (p < 0.0001) than the RT group. The majority were white (88.35%) with advanced FIGO stage III or IVA (72.29 %) disease. Median dose of total radiation was 5720 cGy (IQR 5040-6300) with higher doses observed in the greater than 7 days delay group versus less than 7 days, (p < 0.0001). Median follow up was 27.2 (IQR 11.8-57.9) months. For both cohorts, completion of treatment with delay less than 7 days resulted in significant improvement in median survival when compared to treatment completion delay of more than 7 days: RT (Median OS 34.9 versus 21.6 months, p < 0.01) and CRT (58 versus 41.3 months, p < 0.01). On multivariate subset analysis, both completion of CRT and RT were associated with improved OS when treatment was completed with less than 7 days delay vs greater than 7 days delay, CRT (HR 0.869 [95%CI 0.758-0.997]), RT (HR 0.820 [95%CI 0.698-0.964]). Advanced FIGO stage IVA was associated with the greatest increase in hazard of death, (HR 1.758 [95%CI 1.516-2.039]), compared to FIGO stage II. Conclusions: Completion of radiation with less than 7 days delay is associated with improved overall survival, which is independent of concurrent chemotherapy. These findings suggest that strategies to minimize delays in radiation treatment are crucial in treating locally advanced vulvar cancer.
Impact of clinical trial enrollment on episode costs in the Oncology Care Model (OCM).
Authors: Young Garrett , Bilbrey Larry Edward , Arrowsmith Edward , Blakely L. Johnetta , Daniel Davey B. , Yue Andrew , Chaudhry Basit Iqbal , Spigel David R. , Lyss Aaron J. , Dickson Natalie R. , Fox John , Schleicher Stephen Matthew , Schwartzberg Lee S.
Published: June 2021

6513

Background: Clinical trials are critical for improving outcomes for patients with cancer. However, there is some concern from health insurers that clinical trial participation can increase total cost of care for cancer patients. We investigated the impact of clinical trial participation on total costs paid by Medicare during the OCM program in a large community-based practice. Methods: Tennessee Oncology (TO) is a community oncology practice comprising over 90 oncologists across 30 sites of care. We linked TO trial data and electronic medical record data with OCM data for episodes of care from 2016-2018. To assess the impact of trial participation on total cost relative to routine care, we created matched comparator groups for each OCM episode based on cancer type, metastatic status, number of comorbidities, performance status, and age. Patients with breast cancer receiving hormone therapy only were excluded. Absolute and percent cost differences between groups were calculated for episodes that had a comparator group size of five or greater. Differences in total cost for trial episodes were compared to non-trial episodes, and significance was assessed using the Mann–Whitney U test. We also studied the impact of trial participation on receipt of active treatment in the last 14 days of life (TxEOL), hospice use, and hospitalizations. Results: During the study period, 8,026 completed OCM episodes met study criteria. Patients were enrolled in a clinical trial for 459 of these episodes. On average, episodes during which patients were on trial cost $5,973 less than matched non-trial episodes (Table), independent of early versus late-phase trial. Most savings resulted from decreased drug costs. There were no differences in rates of TxEOL (15% vs. 14% p=1.0), rates of hospitalizations (31% vs. 30% p=0.54), or hospice use (52% vs. 62% p=0.08) between trial and non-trial episodes. Median difference from comparator group average cost was significantly lower for clinical trial episodes (-18% vs. -6%, p<0.01). Conclusions: In the community setting, total costs paid by Medicare for patients participating in clinical trials during OCM episodes were lower than costs for similar patients receiving routine care. Clinical trial participation did not adversely impact end-of-life care or likelihood of hospitalization. These findings suggest that patient participation in clinical trials does not increase total cost of care nor enhance financial risk to payers.[Table: see text]
Bone modifying agents in veterans with castration-resistant prostate cancer.
Authors: Bauman Jordan , Kumbier Kyle , Burns Jennifer A. , Sparks Jordan , Tsao Phoebe A. , Skolarus Ted A. , Shahinian Vahakn B. , Caram Megan Veresh
Published: June 2021

6582

Background: Skeletal related events (SREs) are a known complication for the 80% of men with metastatic prostate cancer who have bone metastases. Previous studies have demonstrated that bone modifying agents (BMAs) such as zoledronic acid and denosumab reduce SREs in men with metastatic castration-resistant prostate cancer who have bone metastases and are now recommended by national guidelines. We sought to investigate factors associated with use of BMAs in Veterans with CRPC across the Veterans Health Administration (VA). Methods: Using the VA Corporate Data Warehouse, consisting of aggregated medical record data from 130 facilities, we used an algorithm previously published to identify men with a diagnosis of castration-resistant prostate cancer (CRPC) based on rising prostate specific antigen (PSA) levels while on androgen deprivation therapy and who received systemic treatment for CRPC with one of the commonly used therapies: abiraterone, enzalutamide, docetaxel, ketoconazole between 2010 and 2017. To account for clustering among facilities, we used a multilevel multivariable logistic regression to determine the association of patient and disease-specific variables on the odds of a patient receiving a BMA after they started treatment for CRPC. Results: Of 4,998 patients with CRPC in our cohort, 2223 (44%) received either zoledronic acid or denosumab at some point after they were initiated on treatment for CRPC. After adjusting for other variables and accounting for a facility, the odds of receiving a BMA decreased by 3% for every additional year of age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and decreased significantly with increasing comorbid conditions (OR 0.94, 95% CI 0.72-0.98 for Charlson Comorbidity Index [CCI] of 1; OR 0.69, 95% CI 0.59-0.81 for CCI 2+). Patients who were Black had 25% lower odds of receiving a BMA than patients who were White (OR 0.75, 95% CI 0.65-0.87). PSA at time of CRPC treatment start had a small but not significant effect on receipt of a BMA (OR 1.04, 95% CI 1.00-1.08) for every unit increase of PSA on the log scale. PSA doubling time was not associated with receipt of a BMA. The presence of a diagnosis code for bone metastases was far lower than expected in this cohort of patients with CRPC (40.7%), and thus was not included in the model. We did not expect the presence of bone metastases to vary significantly among the other independent variables. Conclusions: Despite most patients with CRPC historically having bone metastases, less than half of patients with CRPC received a BMA. Patients who are older, had more comorbidities, or were Black were less likely to receive a BMA after starting treatment for CRPC. Understanding factors that lead to different patterns of treatment can guide initiatives toward more guideline-concordant care.