tbuckley/cabot-search huggingface dataset:
Real-world homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States.
Authors: Daniel J. George, Furaha Kariburyo-Yay, Himani Aggarwal, Jon G. Tepsick, Rebekah Yu, Weiyan Li, Kimmie K. McLaurin, Chinelo Orji, Lincy S. Lal, Sameer R. Ghate
Journal: Journal of Clinical Oncology (2024)

332 Background: Olaparib is one of the first targeted therapies for patients (pts) with mCRPC. This study focused on assessing treatment patterns and results of genetic testing for HRRm in mCRPC pts treated with olaparib monotherapy. Methods: This retrospective study used data abstracted from electronic medical records in the ConcertAI Oncology Dataset with PC diagnosis between 1990 and 2023. Pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. HRRm was defined as a mutation in at least 1 of 14 genes of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L) regardless of test type. Pt demographic and clinical characteristics, patterns of individual HRRm, testing type, and timing of biomarker testing were summarized. The index date was the start date of the earliest olaparib monotherapy treatment. Results: A total of 192 mCRPC olaparib treated pts with at least one HRRm were identified. The median age was 73 years at index date. More than half of pts (56.3%) had an ECOG score of 0 or 1, and 51.0% of pts had a Gleason Score of ≥8 at index. Most pts (87.0%) had bone metastasis at index, and 20.3% had 3 or more sites of distant metastasis. Nearly one-third of pts (31.7%) had documentation of opioid use at index. Over half of the pts (56.2%) had any BRCA mutation ( BRCA2 33.3%, BRCA1 4.7%, co-occurring HRRm 18.2%) and 43.8% had non- BRCA mutation ( ATM 20.8%, CDK12 4.2%, co-occurring HRRm 11.5%, other non- BRCA 7.3%) Over 40% of pts had somatic only testing (40.6%), while 15.1% had germline only testing, 27.6% of the pts had both germline and somatic testing, and 16.7% had other testing. Most pts were tested on or after mCRPC diagnosis (142 pts; 74.0%) and the median time from mCRPC diagnosis to the first biomarker test was 16.9 (IQR 23.3) months. Conclusions: This real-world analysis highlights the need for earlier HRRm testing in pts with mCRPC to allow for optimal timing of novel treatment options that have shown efficacy in a biomarker-selected population. Most pts in this study were tested and diagnosed with HRRm many months after mCRPC diagnosis, at which point they had high levels of bone metastasis, multiple sites of distant metastases, and opioid use at the initiation of olaparib treatment. HRR testing in pts before or at the time of mCRPC would allow for olaparib therapy earlier in the disease course. [Table: see text]
Pembrolizumab plus lenvatinib vs nivolumab plus cabozantinib in patients with metastatic renal cell carcinoma: A matching adjusted indirect comparison (MAIC).
Authors: Pratik Rane, Laura Walton, Manuela Schmidinger, Avivit Peer, Shahrul Mt-Isa, Joseph E. Burgents, Murali Sundaram
Journal: Journal of Clinical Oncology (2024)

399 Background: Nivolumab plus Cabozantinib (nivo/cabo) and Pembrolizumab plus Lenvatinib (pem/len) have been approved and available for patients in first-line metastatic renal cell carcinoma (RCC). There is no direct evidence of the relative efficacy between pem/len and nivo/cabo from head-to-head clinical trials. Therefore, we conducted MAIC to better inform clinical decision-making on treatment choices. Methods: Individual patient data in the intention to treat (ITT) population from KEYNOTE-581 (pem/len vs. sunitinib; 50.1 months median follow-up) were compared to published aggregated data in the same population from CheckMate-9ER (nivo/cabo vs. sunitinib; 44 months median follow-up). Efficacy outcomes compared were overall survival (OS), progression free survival (PFS), objective response rate (ORR) and complete response (CR). Effect modifiers identified included liver/bone metastasis, sarcomatoid features and IMDC risk category. Using a MAIC, KEYNOTE-581 data were reweighted to match the effect modifiers distribution of CheckMate-9ER participants. Then, matching-adjusted hazard ratios (HR) for OS and PFS, and risk difference (RD) for ORR and CR of pem/len vs. sunitinib were calculated using the reweighted KEYNOTE-581 data. Bucher method was subsequently applied to indirectly compare pem/len to nivo/cabo on these outcomes. Two-sided p-values were calculated. Results: MAIC analyses show that, while OS were comparable between treatments (HR: 1.06 [95% CI:0.77,1.48]; p=0.7072), PFS (HR: 0.75 [95% CI:0.56,0.99]; p=0.0457) and ORR (RD: 11.29 [95% CI:1.10,21.49]; p=0.030) showed a statistically significant result in favor of pem/len when compared to nivo/cabo. The CR rate among pem/len users was higher compared to nivo/cabo but was not statistically significant (RD: 5.75 [95% CI:-0.64,12.15]; p=0.078). Conclusions: In first-line metastatic RCC patients, the MAIC shows a statistically significant result in favor of Pembrolizumab plus Lenvatinib in PFS and ORR, and comparable CR and OS benefit.
Outcomes of elderly patients (pts) treated with docetaxel (DOC) for metastatic castration-sensitive prostate cancer (mCSPC): Results from ECHOS, a multicenter Italian observational study.
Authors: Orazio Caffo, Marco Maruzzo, Federico Pravisano, Consuelo ButtIgliero, Mariella Sorarù, Cristina Masini, Stefania Gori, Roberto Sabbatini, Annalisa Pappalardo, Carlo Cattrini, Giuseppe Fornarini, Isabella Vittimberga, Alessandro Rametta, Paolo Andrea Zucali, Emanuela Fantinel, Francesco Grillone, Lucia Fratino, Luca Galli, Monica Giordano, Umberto Basso
Journal: Journal of Clinical Oncology (2024)

153 Background: ECHOS trial is a large real-world study which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, &gt; 1500 pts were included in the study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed the outcomes of pts ≥75 yrs old who received DOC for mCSPC. Methods: We retrospectively and prospectively reviewed the clinical records of a consecutive series of mCSPC pts treated with DOC in the daily clinical practice in 69 Italian Hospitals. The treatment mostly consisted of DOC at the standard dose of 75 mg/sqm every 3 wks for six courses. For each pt we recorded the pre and post-DOC clinical history, the baseline characteristics of the pts, the treatment details and clinical outcomes. For the purpose of the present study, we considered only pts who ended chemotherapy by September 2022. Results: Among 920 mCSPC pts treated with DOC, 132 (14.4%) were ≥ 75 yrs old. Most of them (76%) presented de novo disease with high-volume features. Their baseline characteristics were similar to those of younger pts excepting for baseline hemoglobin levels which were significantly lower in older pts (median 12.6 vs 13.5; p = 0.001). Older pts received either a reduced dose (16.7%) or a modified schedule (8.4%) more frequently than younger one (p &lt; 0.0001). Thirty-six pts experienced a grade 3-4 toxicity, which was mainly hematological (75% of the cases). The median progression-free survival (PFS) was 12.6 mos in older pts compared to 14.9 mos observed in younger ones (p 0.2). The median number of life prolonging agents administered after DOC progression was 1 in pts ≥75 yrs as well as in pts &lt; 75 yrs. The median overall survival (OS) was 27.9 mos and 42.4 mos in older and younger pts, respectively (p &lt; 0.0001). Conclusions: Our data suggest that DOC was efficacious and well-tolerated in mCSPC pts ≥75 yrs although the treatment was administered with either dose or schedule modifications in about 25% of the cases. No differences were observed in terms of PFS between pts ≥75 and ones &lt; 75 yrs. Nevertheless, the median OS of older pts was significantly worse compared to that of younger ones.
Treatment patterns and costs among patients with metastatic renal cell carcinoma (mRCC) in the United States: A real-world study using integrated claims and clinical data.
Authors: Daniel M. Geynisman, Nathan Hill, Lisa Rosenblatt, Xin Yin, Valerie Haley, Chi Nguyen, John Barron, David Vilanova, Saby George
Journal: Journal of Clinical Oncology (2024)

398 Background: The treatment landscape for mRCC has evolved in recent years with the use of tyrosine kinase inhibitors (TKI) and immuno-oncology (IO) therapies. This study examined patient characteristics, treatment patterns, costs, and survival for individuals with mRCC who received either IO-IO or IO+TKI as first-line (1L) regimens. Methods: This retrospective cohort study used an administrative claims dataset from a commercial health plan integrated with clinical data from a cancer care quality program (CCQP) and socioeconomic data from national surveys. Eligible patients began treatment for mRCC between 04/01/2018 and 1/31/2023, were aged ≥ 18 years old, and had ≥ 6 months of health plan enrollment prior to and ≥ 1 month after their 1L treatment. Patient characteristics and 1L and second-line (2L) regimens were described. Costs were summarized per patient per month (PPPM) within time intervals. The Kaplan-Meier method was used to estimate treatment-free interval (TFI) and survival times. Results: The study identified 824 eligible mRCC patients; mean age was 60, 77% were male, and 85% White/6% Black race. Patients receiving 1L IO-IO (n = 471; nivolumab plus ipilimumab) or IO+TKI regimens (n = 353; pembrolizumab plus axitinib [63.7%], nivolumab plus cabozantinib [21.8%], pembrolizumab plus lenvantinib [14.4%]) had similar baseline characteristics with the exception of health plan type, body mass index, and risk score (Table 1). As 2L therapy, patients most often received TKI monotherapy (56%) or IO+TKI (26%). Treatment costs were higher for IO-IO in the first 3 months but lower in subsequent time intervals compared with IO+TKI. Medication costs represented 80% of total costs on average. Between IO-IO and IO+TKI arms, median TFI (1.1 and 1.2 months, respectively) and cumulative survival time (75.1% and 78.3% at 12 months, respectively) were similar. Conclusions: The study described treatment patterns for mRCC and found patients receiving 1L IO-IO and IO+TKI regimens were similar demographically, though IO-IO patients started with poorer risk scores. Although IO-IO was associated with higher treatment costs in the first 3 months, the subsequent monthly costs were lower vs IO+TKI. Results also indicated that retreatment with IO in the 2L setting is occurring in real-world practice.[Table: see text]
Use of the Prostatype P-score to predict adverse pathology (AP) at radical prostatectomy (RP).
Authors: Gerald L. Andriole, Emelie Berglund, Steven Gaal, Vladimir J.N. Bykov
Journal: Journal of Clinical Oncology (2024)

276 Background: Men with low or favorable intermediate risk prostate cancer (PCa) may undergo Active Surveillance (AS) or curative treatment. Among the factors patients and clinicians use to determine which approach to take is the likelihood of AP at RP. Nomograms using clinical parameters alone or along with GC’s have been used to aid in the prediction of AP at RP. The Prostatype test has been developed from prostate biopsy specimens of men with localized PCa. It has been validated in 2 large studies to accurately predict 10-year Prostate Cancer Specific Mortality and 10-year Prostate Cancer Metastasis. The Prostatype test is generated from the signature of 3 embryonic stem cell genes (IGFBP3, F3, and VGLL3) measured from the biopsy along with clinical data (PSA, Gleason Score, and T-stage). Its intended use is to guide treatment decisions in men currently on or considering AS. The Prostatype test is CE marked and is available for clinical use in Europe. Methods: To validate the ability of the Prostatype test performed on prostate biopsy tissue to predict AP (Gleason score 4+3 or higher and/or non-organ confined disease (pT3)) at RP, we studied 214 patients (Median age 65 (59,68); Median PSA 7.6 (5.3, 11.1); 20% Gleason 6; 64% Gleason 7; 16% Gleason &gt;8) who underwent RP, of which 117 (55%) had AP. The model to predict AP at RP is an Artificial Neural Network (ANN) algorithm. Results: This ANN showed excellent performance, e.g., great balance between precision and sensitivity and had a high overall accuracy (AUC of 0.88) at predicting AP at RP. This 5-layer ANN model includes IGFBP3, F3, % positive biopsies and biopsy primary Gleason score. Confusion matrix measurement of the performance of the model shows it minimizes misclassification of patients with AP, and together with the Matthews Correlation coefficient (0.639) provides evidence that the ANN model manages false positives and false negatives correctly. Conclusions: This study shows that the Prostatype test is a strong predictor of AP at RP and may be used to guide decision making of clinicians and patients who are currently on or considering AS.
Characteristics and outcomes of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) showing a primary resistance (PR) to docetaxel (DOC): Results from a large real-world database.
Authors: Orazio Caffo, Consuelo ButtIgliero, Paola Ermacora, Mariella Sorarù, Stefania Di Girolamo, Roberto Sabbatini, Stefania Gori, Gaetano Facchini, Carlo Cattrini, Andrea Marchetti, Francesca Valcamonico, Francesca Vignani, Vincenza Conteduca, Donata Sartori, Carmen Barile, Emanuele Naglieri, Nicola Calvani, Alessia Cavo, Claudia Biasini, Davide Bimbatti
Journal: Journal of Clinical Oncology (2024)

158 Background: ECHOS trial is a large real-world study, which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, &gt; 1500 pts were included in the study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed the characteristics and outcomes of mCSPC pts progressing within 6 mos from the start of DOC. Methods: We retrospectively and prospectively reviewed the clinical records of a consecutive series of mCSPC pts treated with DOC in the daily clinical practice in 69 Italian Hospitals. The treatment mostly consisted of DOC at the standard dose of 75 mg/sqm every 3 wks for six courses. For each pt we recorded the pre and post-DOC clinical history, the baseline characteristics of the pts, the treatment details and clinical outcomes. For the purpose of the present study, we considered only pts who ended chemotherapy by September 2022. PR was defined as the onset of progressive disease within 6 mos from the DOC start. Results: Among 920 mCSPC pts treated with DOC, 122 (14.3%) were PR. Most of them (95.6%) presented a de novo (DN) disease, which showed mostly high volume (HV) features (82.3%). Compared to the pts without PR, those showing PR presented more frequently a visceral involvement (26.2% vs 18.2%; p = 0.038), had lower baseline levels of hemoglobin (12.8 g/dl vs 13.4 g/dl; p &lt; 0.0001), and higher baseline levels of lactate dehydrogenase (266 U/L vs 220,5 U/L; p &lt; 0.002). No other significant differences were observed in terms of baseline PSA and alkaline phosphatase levels, symptoms degree, disease volume and timing of mets presentation between PR e no-PR pts. The median number of life prolonging agents administered after DOC progression was 1 in pts with PR as well as in pts without PR. The median overall survival was 11.9 mos and 44.9 mos in PR and no-PR pts, respectively (p &lt; 0.0001). Conclusions: Our data suggest that PR led a significant worsening of prognosis with a relevant shortening of life expectancy in pts who receive DOC for mCSPC.
Diagnosis of prostate cancer and benign prostatic hyperplasia based on urinary cell-free DNA methylation characteristics.
Authors: Jindan Luo, Hang Dong, Haoran Tang, Jiahe Yi, Pan Du, Shidong Jia, Liping Xie
Journal: Journal of Clinical Oncology (2024)

275 Background: Distinguishing between early-stage prostate cancer (PCa) and benign prostatic hyperplasia (BPH) has posed a persistent clinical challenge. Exploring the epigenetic characteristics of urinary cell-free DNA (ucfDNA) offers potential for improving diagnosis. In this preliminary study, we aimed to investigate the feasibility of utilizing of urinary cfDNA methylation features as a non-invasive way to detect PCa. Methods: Paired tissue, plasma, and urine samples were collected from 12 PCa patients, along with paired plasma and urine samples from 12 BPH patients, and urine samples from 24 healthy donors. PredicineEPIC, a whole genome-based DNA methylation assay, was implemented to profile methylation features in all these samples. Results: We discovered that the methylation patterns of ucfDNA more closely resembled those of tumor tissue compared to plasma cfDNA, suggesting that urine can serve as an effectual alternative to blood for detecting cancer related signals. We identified 369 differentially methylated regions that contained PCa-specific methylation signals. Subsequently, we employed feature selection and applied a machine learning regression algorithm to construct a classification model. Validation on an independent GEO dataset yielded an impressive AUC of 0.83 for distinguishing between PCa and benign prostatic hyperplasia (BPH). Conclusions: This study demonstrated the potential of ucfDNA-based methylation markers in the early detection of prostate cancer.
Enzalutamide combination treatment (tx) suspension in men with high-risk biochemically recurrent (BCR) prostate cancer: Outcomes from EMBARK.
Authors: Stephen J. Freedland, Paul R. Sieber, Martin Gleave, Ugo De Giorgi, Bryan Allyn Mehlhaff, Daniel Costin Danila, Curtis Dunshee, Costas D. Lallas, Marc Pliskin, Yiyun Tang, Gabriel P. Haas, Matt Rosales, Jamal Christo Christo Tarazi, Fabian Zohren, David Russell, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

156 Background: The 3-arm EMBARK trial found statistically superior and clinically meaningful improvements in metastasis-free survival (MFS) with enzalutamide + leuprolide acetate (enza combo) and enza monotherapy vs placebo + leuprolide (alone) in patients (pts) with high-risk BCR prostate cancer. Tx was suspended at week 37 in 321 (90.9%) pts in the enza combo arm and 240 (67.8%) in the leuprolide-alone arm based on prostate-specific antigen (PSA) response. Outcomes in the enza combo vs leuprolide-alone arms by tx suspension status are reported. Methods: The phase 3 EMBARK study enrolled pts with high-risk BCR, defined as PSA doubling time ≤9 months, and PSA ≥2 ng/mL above nadir post-radiotherapy (RT) or ≥1 ng/mL after radical prostatectomy (RP) ± postoperative RT. Pts were randomized 1:1 to enza 160 mg/day + leuprolide (22.5 mg every 12 weeks) or leuprolide alone. Tx was suspended at week 37 if serum PSA was &lt;0.2 ng/mL at week 36 and restarted when PSA reached ≥2 ng/mL (primary RP) or ≥5 ng/mL (no primary RP). A secondary endpoint was the proportion of pts with undetectable PSA 2 years after suspension. MFS (per blinded independent central review) was analyzed descriptively between tx arms by suspension status. P-values were nominal. Results: The 3-year MFS rate (95% CI) in the suspension group was 94.4% (91.2–96.5%) with enza combo and 90.0% (85.3–93.2%) with leuprolide alone; in the no suspension group, 3-year MFS rates were 76.2% (33.2–93.5%) and 66.9% (55.4–76.1%), respectively. MFS in the suspension group was improved with enza combo vs leuprolide alone (HR 0.470, 95% CI 0.308–0.717; P=0.0003); no difference in MFS was observed in the no suspension group (HR 0.719, 95% CI 0.225–2.295; P=0.5763), although sample size was small for enza combo (n=9). Compared with no suspension, a higher proportion of pts in the suspension group received prior RP and a lower proportion received prior RT (Table). Two years after suspension, 16.8% (95% CI, 12.9–21.4%) of enza combo pts and 9.6% (95% CI, 6.2–14.0%) of leuprolide-alone pts had undetectable PSA ( P=0.0089). Conclusions: MFS was improved with enza combo vs leuprolide alone for pts with BCR who suspended tx. No difference in MFS was observed in the no suspension group, but firm conclusions were precluded by the limited number of pts who did not suspend tx with enza combo. Pts who suspended tx had higher rates of prior RP vs those who did not. Pts who had received enza combo prior to tx suspension were more likely to have undetectable PSA 2 years thereafter compared with those who received leuprolide alone. Clinical trial information: NCT02319837 . [Table: see text]
Outcomes with neoadjuvant chemotherapy in bladder-preserving treatment for MIBC.
Authors: Michael Glover, Agnes Ewongwo, Melissa Usoz, Zachary Kornberg, Hilary Bagshaw, Jay Bakul Shah, Sumit Shah, Yushen Qian
Journal: Journal of Clinical Oncology (2024)

577 Background: Trimodality bladder preservation is an acceptable alternative to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC). Multiple retrospective studies have reported similar disease control rates and overall survival rates with chemoradiation (CRT), but the benefit of neoadjuvant chemotherapy (NAC) prior to CRT is not established. This study investigates the outcomes of CRT with or without NAC for management of MIBC. Methods: Retrospective analysis of 135 adult patients with muscle invasive bladder cancer evaluated in the Department of Radiation Oncology over 7 years (2016-2022). Patients were excluded if they did not receive NAC or if they underwent RC. Patients were treated with NAC followed by CRT. Overall survival (OS), progression-free survival (PFS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier methods. Follow-up was censored at 36 months after treatment. Differences in survival outcomes by completion of status of NAC were analyzed using log-rank tests. All survival analyses were performed in SAS version 9.4. Results: Of the 135 evaluated patients, 38 were treated with NAC followed by CRT. The 24-month OS, PFS, and MFS were 76% [95% CI 62-92%], 60% [95% CI 46-79%], and 72% [95% CI 58-90%] respectively. The 24-month PFS in patients who received a full course of NAC was 66.0% [95% CI 50-87%]) and 38.0% [95 CI 15-92%] in those who did not complete NAC regimen. Overall PFS was significantly higher in the NAC cohort (log-rank p=0.03). There was no significant difference in OS between patients who completed prescribed course of NAC versus those who did not (log-rank p=0.48). Treatment was overall well tolerated with 28.2% of grade 2 or higher RT toxicity. Conclusions: NAC prior to CRT achieved excellent short term disease-free and survival outcomes in patients with non-metastatic MIBC. This analysis is limited by its retrospective nature but suggests that completion of NAC prior to CRT may be associated with lower rates of disease recurrence. [Table: see text]