tbuckley/cabot-search huggingface dataset:
Underutilization of androgen deprivation therapy (ADT) intensification for the treatment of men with metastatic hormone-sensitive prostate cancer (mHSPC): A systematic review of real-world database studies.
Authors: Amit D Raval, Stephanie Chen, Natasha Littleton, Niculae Constantinovici, Peter J. Goebell
Journal: Journal of Clinical Oncology (2024)

66 Background: In the last decade, intensification of ADT with chemotherapy or androgen receptor pathway inhibitors (ARPi) has shown clinical benefits for men with mHSPC compared to ADT alone and has been recommended for mHSPC in clinical guidelines. The transition of these guidelines into real-world practice was investigated by several studies; however, these data have not been systematically summarized across the globe. Thus, we conducted a systematic literature review of real-world database (RWD) studies to summarize treatment patterns in mHSPC. Methods: An electronic search was performed in PubMed and Embase (covering citations until July 2023) and for relevant conferences of the past 2 years to identify RWD studies examining treatment patterns in men with mHSPC. Treatment patterns were summarized by overall study population across major geographies and factors associated with ADT intensification were described. Results: Of 2,325 retrieved citations, 29 studies met the inclusion criteria, with a total of 344,473 men with mHSPC covering study periods from 2014 to 2021. Most were cohort studies (n=26), utilizing electronic medical records (EMR)/chart reviews (n=18), and with RWDs from the United States (US) (n=21), followed by Europe (n=8), and Asia (n=6). Most studies included men with a median age of ≥70 years (n=23) and &gt;80% of men had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1 (n=5 of 8). In the US, most studies showed that ADT monotherapy was predominantly utilized (&gt;50%), followed by ADT/ARPi (20-40%), and ADT/chemotherapy (10-20%). Abiraterone was the most frequently used ARPi followed by enzalutamide. In Europe, most studies also reported ADT monotherapy (&gt;45%), followed by ADT/ARPi (11-25%), or ADT/chemotherapy (12-34%). In Asia, ADT monotherapy (&gt;62%) was the most common treatment in most studies, with low use of ADT/ARPIs (&lt;20%), and ADT/chemotherapy (&lt;15%). A few studies with recent EMR data (covering the 2020-21 data period) from cancer centers/registries showed high use of ADT/ARPi (&gt;40%) in both the US and Europe. Reported quantitative factors (n=13) associated with intensification beyond ADT were high disease burden (spread of metastases, high volume), young age, ECOG PS 0/1, low comorbidities, and treating physician specialty-oncologist; qualitative factors (n=2) were patient preference, unsatisfactory response to ADT treatment, ability to tolerate adverse events, and lack of cost barriers. Conclusions: This comprehensive review shows ADT monotherapy remained highly utilized across major geographies until 2021 despite new evidence and updated guideline recommendations. However, the utilization of intensified treatment with ARPi combinations is slowly increasing after the recent approvals in mHSPC.
Association between PET-based TheraP eligibility and <sup>177</sup>Lu-PSMA-617 (LuPSMA) outcomes in VISION-eligible patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ridvan Arda Demirci, Roman Gulati, Alireza Ghodsi, Peter Nelson, Heather H. Cheng, Jessica E. Hawley, Todd Yezefski, Michael C. Haffner, Robert Bruce Montgomery, Michael Thomas Schweizer, Evan Y. Yu, Delphine L Chen, Amir Iravani
Journal: Journal of Clinical Oncology (2024)

41 Background: The optimal threshold based on pre-treatment PET for patient selection for LuPSMA is yet to be defined. TheraP trial applied a high threshold for PSMA-expression on PSMA PET and utilized FDG PET to exclude FDG-avid/non-PSMA-avid disease while the VISION trial used only PSMA PET with a lower threshold of PSMA-expression. The stricter criteria in TheraP trial doubled the screening failure rate compared to VISION trial, 28% vs. 12.6%. In this study among VISION-eligible patients, we aimed to compare the outcome of those who were TheraP-Eligible (TheraP-E) to TheraP-Ineligible (TheraP-I). Further, the prognostic value of FDG-PET phenotyping is investigated. Methods: This retrospective cohort study evaluated consecutive VISION-eligible mCRPC patients who received at least one cycle of LuPSMA and had both PSMA- and FDG-PET within one month of each other between June 2022 and January 2023. Patients were blindly classified as TheraP-E vs. TheraP-I. We compared whole-body semiquantitative parameters including total tumor volume (TTV), SUVmean and SUVmax and outcomes including PSA decline of ≥50% relative to baseline (PSA50), PSA-progression-free survival (PSA-PFS), and overall survival (OS) between the groups. Separately, the patients were dichotomized to having dominant FDG-avid disease (uptake &gt; liver in most sites of disease) vs. non-FDG-avid disease and OS were compared by Cox-regression. Results: 46 patients (median age: 72, ECOG 0-2: 89%, visceral disease: 28%) were included with a median follow-up of 10 months (IQR: 8-14). 14/46 (30%) patients assessed as TheraP-I and had lower PSMA-PET SUVmean and SUVmax compared to TheraP-E patients (5.6 vs. 8.8 and 23 vs. 53, p &lt; 0.001 for both) while other PET parameters including PSMA TTV and FDG parameters (SUVmax, SUVmean and TTV) were not statistically different. TheraP-I patients had lower PSA50 response (21% vs. 56%, p = 0.029) but PSA-PFS and OS were not significantly different compared to TheraP-E patients (Table). 37/46 (80%) patients assessed as FDG-avid had an increased risk of death compared to non-FDG-avid counterparts (Table). Conclusions: In a VISION-eligible population receiving LuPSMA, TheraP imaging-based ineligibility was associated with worse PSA response but with no significant difference in PSA-PFS or OS. Clinical investigation of the more permissive VISION inclusion criteria and the importance of FDG-avid disease using a larger sample size is warranted. [Table: see text]
A real-world observational study characterizing patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) treated with or without androgen receptor pathway inhibitors (ARPIs).
Authors: Michael Paul Kolinsky, Dylan E. O'Sullivan, Devon J. Boyne, Darren R Brenner, Simran Shokar, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2024)

59 Background: mCSPC treatment is rapidly evolving with androgen deprivation therapy (ADT) plus ARPIs viewed as the standard of care for most pts. Data are needed to understand the real-world characteristics and treatment patterns of mCSPC (PC) pts in this dynamic field. This study aimed to define clinical features of mCSPC pts, estimate the proportion of pts receiving ARPIs, and evaluate clinical and demographic features associated with ARPI use. Methods: This retrospective cohort study used data from electronic health records and administrative databases in the province of Alberta, Canada. All newly diagnosed metastatic PC pts between 2017-2020 were identified. Pts were considered to have mCSPC if they initiated ADT within 30 days prior to, or at any time after diagnosis. ARPI exposure was defined as receiving ARPI within 180 days of initiating ADT. ARPI-naïve pts may have received ADT alone or other non-ARPI therapy (i.e., docetaxel) within 180 days of initiating ADT. Multivariable logistic regression was used to evaluate pt characteristics related to the receipt of ARPI. Overall survival (OS) was defined as the date of diagnosis to death from any cause or last known contact. Results: Of the 976 mCSPC pts identified, 33.5% received an ARPI. In ARPI exposed pts, the median time from ADT to ARPI start was 7.9 weeks and median time on ARPI was 13.1 months (mos). In multivariable analyses, ARPI use was associated with younger pt age, more recent diagnosis, fewer comorbidities, a higher metastatic burden, treatment centre, referral to a medical oncologist, and prior local therapy (all p&lt;0.05). The median time to next therapy was 24.6 mos (95%CI=19.5-33.0) vs. 18.5 mos (95%CI+16.9-21.1), and median OS was 38.5 mos (95%CI=32.8-NA) vs. 34.2 mos (95%CI=33.3-38.8) for APRI exposed vs. ARPI-naive pts, respectively (p=0.03). Conclusions: This study identified factors associated with ARPI use in mCSPC, potentially allowing targeted efforts to improve ARPI uptake for pts in whom use is low. These findings are important as they reflect outcomes seen in real world pts.
Interim analyses from the PROSPET-BX trial: [<sup>G8</sup>Ga]PSMA PET/CT vs. mpMRI in patients with suspicion of prostate cancer and previous negative biopsy.
Authors: Egesta Lopci, Massimo Lazzeri, Luca Disconzi, Piergiuseppe Colombo, Alberto Saita, Roberto Peschechera, Vittorio Fasulo, Davide Maffei, Roberta Zanca, Paolo Casale, Marcello Rodari, Giorgio Ferruccio Guazzoni, Luca Balzarini, Nicolo' Buffi, Giovanni Lughezzani
Journal: Journal of Clinical Oncology (2024)

282 Background: Herein we present the results of the interim analyses of our prospective trial (Identifier: NCT05297162), designed to compare [ 68 Ga]PSMA PET/CT with mpMRI in men with a high suspicion of prostate cancer (PCa) after at least one previous negative biopsy. Methods: From April 2022 until September 2023, overall, 94 patients were screened, 78 were enrolled and 64 completed all study investigations. Inclusion criteria: PSA&gt;4.0ng/ml; free-to-total PSA ratio &lt;20%; progressive rise of PSA levels in two consecutive samples; at least one previous negative biopsy; negative digital rectal examination. [ 68 Ga]PSMA PET/CT and 3T mpMRI were performed within one month, followed by TRUS-fusion prostate biopsy. Target lesions were defined based on PI-RADS v2.1 for mpMRI and Primary Score, SUVmax and SUVratio for [ 68 Ga]PSMA PET/CT, then correlated to pathology findings. Results: Median age was 64 years (range 51-83) and median PSA 10.4 ng/ml (range 4.3-25,9). Most patients (76.6%) had one previous negative biopsy. According to re-biopsy results, 10 patients presented with clinically significant PCa (csPCa), 4 with GS 6, while the majority had a negative biopsy (78%). mpMRI results were: 40 patients with PI-RADS 2 (62.5%), 3 with PI-RADS 3 (4.7%), 15 with PI-RADS 4 (23.4%), and 6 with PI-RADS 5 (9.4%). Primary scores were: 45 score 1-2 (70%), and 19 score 3-5. PI-RADS and Primary scores were significantly correlated (P=0.0006). Median SUVmax and SUVratio were 3.7 and 1.35 for benign versus 8.9 and 3 for malignancy, respectively (P&lt;0.001). ROC analyses identified optimal cut-off points for csPCA, with SUVmax&gt;7.48 (AUC 0.756; 95%CI 0.633-0.855) and SUVratio&gt;2.79 (AUC 0.748; 95%CI 0.624-0.848). PI-RADS, Primary score, SUVmax and SUVratio proved significantly associated to biopsy results. When combining [ 68 Ga]PSMA PET/CT with mpMRI data, the detection rate was 90% for csPCa, and the combination of both modalities could spare 87.5% of unnecessary re-biopsies. Conclusions: In these interim results, [ 68 Ga]PSMA PET/CT parameters predict biopsy results as mpMRI in patients who are candidates to re-biopsy; the combination of both modalities can spare most unnecessary re-biopsies, by granting a 90% detection rate for csPCa. Clinical trial information: NCT05297162 .
Real-world comparison of prostate-specific antigen (PSA) response in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or enzalutamide (ENZ).
Authors: Benjamin H. Lowentritt, Shawn Du, Dominic Pilon, Ibrahim Khilfeh, Erik Muser, Carmine Rossi, Frederic Kinkead, Lilian Diaz, Jill Korsiak, Lorie Ellis, Patrick Lefebvre, Gordon Andrew Brown
Journal: Journal of Clinical Oncology (2024)

51 Background: APA and ENZ, two androgen receptor synthesis inhibitors (ARSIs), used in combination with androgen deprivation therapy (ADT) are among the recommended treatments for patients with mCSPC. Deep PSA response, evaluated as ≥90% PSA decline (PSA90), is an important outcome after ARSI initiation, with early, deep response associated with longer survival. The primary objective of this study was to compare PSA90 response in ARSI-naïve patients with mCSPC by 6 months after initiating APA or ENZ in real-world clinical practice. Methods: Linked electronic medical record (EMR) data of US community urology practices in the from PPS Analytics and administrative health data from Komodo Health Solutions Research Database were evaluated. Patients with mCSPC were selected into two cohorts, based on the index date, defined as the first paid pharmacy claim or in-office dispensation for APA or ENZ on or after 16 Dec 2019. Patients were required to have ≥12 months of pre-index EMR clinical activity. Pre-index characteristics (i.e., age, race, geographic region, payer type, index year, time from metastasis, time from first prostate cancer [PC] diagnosis, de novo PC, ADT use, first-generation antiandrogen use, chemotherapy use, metastasis locations, most recent PSA level, testosterone level, and Gleason score) were balanced between cohorts with inverse-probability treatment weighting (IPTW). Patients were followed from index date until the earliest of index ARSI discontinuation or switch, radiopharmaceutical initiation, end of open administrative claim or EMR clinical activity, or end of data availability (30 Sep 2022). PSA90 was defined as the earliest ≥90% decline in PSA relative to most recent pre-index PSA. The proportion of patients achieving PSA90 was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: In total 860 APA and 869 ENZ patients were identified. Patient pre-index characteristics were balanced with IPTW (Table). By 6 months post-index, 80.3% of APA and 75.0% of ENZ patients had ≥1 PSA test result. By 6 months, significantly more APA patients attained a PSA90 response, as compared to ENZ patients (p=0.005; Table). The median time to PSA90 response was 3.5 months for APA and 4.9 months for ENZ. Conclusions: This US real-world study of patients with mCSPC demonstrated that treatment with APA produces a deep, early PSA response by 6 months in a greater percentage of patients than treatment with ENZ. [Table: see text]
Real-world survival of men with metastatic castration-sensitive prostate cancer (mCSPC) initiated on apalutamide (APA) or enzalutamide (ENZ) in an oncology database: ROME Study.
Authors: Mehmet Asim Bilen, Shawn Du, Ibrahim Khilfeh, Carmine Rossi, Jill Korsiak, Alvi Rahman, Patrick Lefebvre, Dominic Pilon, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

57 Background: Androgen receptor signaling inhibitors (ARSIs), including APA and ENZ, have demonstrated progression-free and overall survival benefits for men with mCSPC in the clinical trial setting, but data evaluating real-world treatment effectiveness remains limited. The aim of this study was to describe real-world survival among men with mCSPC who initiated APA or ENZ in the United States (US). Methods: In this retrospective longitudinal cohort study, clinical data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry Electronic DataMart (1/1/2013–05/31/2023) were used. Patients with chart-confirmed metastasis and without castration resistance were classified into two treatment cohorts based on earliest initiation of APA or ENZ on/after 12/16/2019 (index date). Patients had ≥12 months of clinical data pre-index and were followed from the index date until the earliest of 24 months post-index, end of clinical activity, or end of data availability. Patients’ date of death was obtained from electronic medical records, Social Security Death Index, or other confirmed sources. Using an intention-to-treat approach, Kaplan-Meier analysis was used to describe the proportion of patients surviving by 24 months post-index. An unadjusted Cox proportional hazards model was used to describe crude differences in survival rates between patients initiating APA and ENZ. Results: There were 234 APA (mean age: 73.2 years; 59.8% White, 13.7% Black) and 527 ENZ (mean age: 73.9 years; 55.2% White, 13.1% Black) patients included in this study (Table). APA median time on-treatment was 10.9 months over a median observation period of 13.3 months, while ENZ median time on-treatment was 11.1 months over a median 14.8 months observation period. By 24 months, a higher proportion of patients in the APA cohort survived than in the ENZ cohort (85.4% vs 73.9%; unadjusted hazard ratio=0.59, 95% confidence interval: 0.39, 0.95; p=0.030; Table). Conclusions: In this real-world analysis of patients with mCSPC, more patients treated with APA survived by 24 months following treatment initiation as compared to treatment with ENZ. While the current study reports unadjusted analyses, future studies adjusting for potential confounding variables should be conducted to confirm these findings in order to inform clinicians on treatment selection for patients with mCSPC. [Table: see text]
Clinical and patient factors associated with treatment intensification for metastatic castration-sensitive prostate cancer.
Authors: Sreevalsa Appukkuttan, Troy Williams, Jay Jhaveri, David Campbell, Sheldon Kong, Bashir Kalayeh, Scott David Ramsey
Journal: Journal of Clinical Oncology (2024)

63 Background: Intensified therapies convey a survival advantage over androgen deprivation therapy (ADT) alone in metastatic hormone sensitive prostate cancer (mHSPC). We sought to identify area- and patient-level factors that are associated with intensification of therapy among mHSPC patients treated in US health systems. Methods: Electronic health records from OPTUM were used to identify patients aged ≥18 with mHSPC who received ADT between 2020 and 2022. Treatment intensification was defined as receiving one of the following within 90 days of initiation of ADT: apalutamide, enzalutamide, abiraterone +/- prednisone +/- docetaxel, darolutamide +/- docetaxel, docetaxel +/- other systemic therapy, and external beam radiation therapy (EBRT). Multivariable logistic regression was used to determine factors associated with intensification. We used Chi-squared tests to select the model with the best statistical fit. Results: We identified 1,123 patients with mHSPC who received ≥1 ADT in the post-index period with mean age of 71.2 (9.5), 73% Caucasian, 18% African American, and 2% Asian. Overall, 640 (57%) patients received treatment intensification within 90 days of ADT initiation. The proportion of patients receiving intensification increased from 53% to 63% between 2020 and 2022. The most common intensification treatments were abiraterone acetate (46%) and enzalutamide (38%). The median time to first treatment after metastasis was 15 days for receiving intensified therapy and 34 days for non-intensified therapy. In multivariable logistic regression, younger age, presence of bone/bone marrow metastasis at baseline, region (Northeast and West), and lower modified Charlson Comorbidity Index (CCI) score (excluding cancer) were significantly associated with receiving intensified therapy (Table). PSA was not included in models due to substantial missingness (40%). Conclusions: Just over half of eligible patients received treatment intensification following ADT. There are also significant disparities in treatment by age, region, and site of metastases. Future studies examining physician and patient preferences for intensification, as well as possible misperceptions and biases, would provide evidence to address undertreatment in this setting. [Table: see text]
Prostate-specific antigen (PSA) response among patients with metastatic castration-sensitive prostate cancer (mCSPC) initiated on apalutamide (APA) or abiraterone acetate (ABI) in real-world urology practices.
Authors: Gordon Andrew Brown, Ibrahim Khilfeh, Shawn Du, Carmine Rossi, Lilian Diaz, Frederic Kinkead, Erik Muser, Jill Korsiak, Patrick Lefebvre, Dominic Pilon, Lorie Ellis, Benjamin H. Lowentritt
Journal: Journal of Clinical Oncology (2024)

53 Background: Recently approved oral therapies APA and ABI (plus prednisone) are effective mCSPC treatments. Prior real-world evidence showed that, relative to ABI, patients who initiated APA had significantly higher rates of PSA decline ≥90% (PSA90), which has been associated with longer overall survival. The objective of this study was to compare PSA90 response among an enhanced cohort of patients with mCSPC initiated on APA or ABI. Methods: Electronic medical records from PPS Analytics including data from US community urology practices were linked with administrative claims from the Komodo Health Solutions Research Database. Androgen receptor signaling inhibitor (ARSI)-naïve patients with mCSPC with ≥12 months of pre-index clinical activity were selected into the APA or ABI cohort based on their first paid claim/dispensation on or after 17 Sep 2019 (index date). Patients were followed to earliest of index ARSI discontinuation or switch, radiopharmaceutical use, end of insurance or clinical activity, or end of data availability (30 Sep 2022). Inverse probability treatment weighting (IPTW) was used to reduce potential pre-index confounding, controlling for age, race, region, insurance payer, index year, time from metastasis to index date, time from first prostate cancer (PC) diagnosis to index date, metastasis locations, de novo PC, use of androgen deprivation therapy, first-generation antiandrogens or chemotherapy, most recent PSA and testosterone levels, and most recent Gleason score. PSA90 was defined as the earliest attainment of ≥90% decline in PSA relative to pre-index (most recent value within 13 weeks). The proportion of patients achieving PSA90 was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: A total of 917 APA and 632 ABI patients were identified. Patient characteristics were balanced with IPTW (Table). By 6 months post-index, 80.9% of APA and 72.8% of ABI patients had a PSA measurement. By 6 months, significantly more APA patients attained a PSA90 response, as compared to ABI patients (P &lt; 0.001; Table). Median time-to-PSA90 was 3.5 months for APA patients and 8.8 months for ABI patients. Conclusions: This real-world study supports previous findings that a greater percentage of patients with mCSPC in the US initiating APA achieved deep PSA response compared to those initiating ABI. [Table: see text]