tbuckley/cabot-search huggingface dataset:
Outcomes with first-line ipilimumab and nivolumab for patients with metastatic renal cell carcinoma by number of doses.
Authors: Sahil D Doshi, Andrea Lopez Sanmiguel, Andrea Knezevic, Ritesh R Kotecha, Neil J. Shah, Marie Carlo, Darren R. Feldman, Robert J. Motzer, Martin H Voss
Journal: Journal of Clinical Oncology (2025)

540 Background: Ipilimumab (IPI) and nivolumab (NIVO) are standard first-line systemic therapy for patients with metastatic renal cell carcinoma (RCC). The regimen is administered in combination once every 3 weeks for 4 doses, followed by NIVO maintenance. The dose and frequency of IPI appears to correlate with treatment safety and tolerability across cancer types. Further, studies in advanced melanoma have demonstrated that the efficacy of IPI + NIVO is largely driven by the first two doses in many patients (Postow MA et al., J Clin. Oncol. 2022). We assessed outcomes with IPI + NIVO by number of doses given in patients with metastatic RCC. Methods: We conducted a retrospective study of patients with metastatic RCC at Memorial Sloan Kettering Cancer Center treated with first-line IPI + NIVO. Baseline characteristics and treatment outcomes were obtained from electronic health record review. We calculated overall survival (OS) by the Kaplan-Meier method starting at 12 weeks after initiation of combination therapy, including all patients who were still alive and being followed at that time point and excluding those who had disease progression prior to completing 4 doses. We compared survival rates at 12 and 18 months and median OS for patients who received 4 doses versus those who received fewer than 4 doses. Results: Patients with metastatic RCC treated with first-line IPI + NIVO were included (N=222); 77% were male, 85% had clear cell RCC, 48% had sarcomatoid and/or rhabdoid features, and 87% had IMDC intermediate or poor risk disease. Regarding IPI + NIVO, 145 patients (65%) received all 4 doses, 30 (14%) received 3 doses, 21 (9%) received 2 doses, and 26 (12%) received 1 dose. The most common reasons for not completing all 4 doses (77, 35%) were toxicity (57%) and disease progression (21%). All 145 patients who received 4 doses and 44 who received fewer than 4 doses for reasons other than early progression or death were included in the analysis. OS in the 4 dose and &lt;4 dose group at 18 months was 83% (95% CI: 76%, 89%) and 79% (95% CI: 63%, 88%), respectively. Conclusions: In this observational analysis, we found comparable OS rates in those patients who received all 4 doses of IPI + NIVO compared to those who received fewer than 4 doses for reasons other than disease progression, primarily toxicity. Four Doses of IPI + NIVO (N=145) Fewer Than Four Doses of IPI + NIVO, Excluding Early Disease Progression (N=44) 12-month OS (95% CI) 89% (82%, 93%) 86% (72%, 94%) 18-month OS (95% CI) 83% (76%, 89%) 79% (63%, 88%) Median OS, months (95% CI) 67.1 (40.1, NR) 82.5 (27.1, 109.3) Log-rank p value = 0.595
Understanding health inequalities based on socio-economic factors and geographical location in renal cell carcinoma: A large-scale national cohort study in England.
Authors: Prantik Das, Joshua Owide, Rania Mohammed
Journal: Journal of Clinical Oncology (2025)

464 Background: Kidney cancer is 7 th most common cancer in England with renal cell carcinoma (RCC) accounting for about 80% of all cases of kidney cancer. It has well established that the incidence and mortality rates of RCC are strongly associated with four main risk factors, including family history, lifestyle, environment, and occupation. In addition, unequal access to improvements in RCC cancer treatment and limited access to screening and diagnosis, significantly contribute to the difference observed in survival rate. Methods: We aim to assess the association between area-level measures of socioeconomic deprivation, from the 20% most deprived of the population (quintile 1) to the 20% least deprived (quintile 5), or geographical regions in England, with both the diagnosis and treatment of RCC, over five years from April 2019 to March 2024. This study utilized patient-level data for primary and metastatic renal cancer (ICD-10: C64) by organisation, procedure, ethnicity, age group and deprivation quintile from Hospital Episode Statistics (HES). Results: Among 54,535 included patients, 9,935 (18.2%) came from the most deprived quintile and 11,330 (20.8%) from the least deprived quintile with a mean age of 62 years across all patients. Of included patients, 43,290 (79.3%) were Caucasian (white) and the remaining 14,235 patients came from other ethnic groups. In total, 61.0% of patients were middle aged (aged from 45 to 74), with 35.0% elderly (75 and above) and 5.4% classed as young (below 45). Caucasian populations have higher rates of metastatic disease (34.6%) vs non white (29.6%). Prevalence of metastatic disease increases with age (24.1% vs 33.3% vs 34.6% in young, middle aged and elderly respectively). Higher deprivation is associated with lower rates of nephrectomy (42.3% in most deprived vs 43.6% in least deprived). Patients in areas of higher deprivation are on average younger than those in least deprived areas (57 years in most deprived vs 64 in least deprived) while non-white renal cancer patients are also typically younger (57 non-white vs 64 white). The Midlands (central England) region is associated with the highest rates of metastatic cancer (37.4%) while North East &amp; Yorkshire (30.8%) and London (31.1%) has the lowest metastatic disease rates. Conversely, total nephrectomy rates are highest in North East &amp; Yorkshire while they are lowest in the South West region and London (46.6% vs 42.8% vs 43.0% respectively). Conclusions: This study presents the most recent and extensive RCC data from England, exploring the impact of socioeconomic status and geographical location in diagnosis and management of RCC. These findings could facilitate targeted initiatives to improve health inequity across regions in England.
Addition of darolutamide to first line treatment of metastatic castration-resistant prostate cancer (mCRPC): A randomized open label phase II trial (SAKK 08/23).
Authors: Ursula Vogl, Katrin Eckhardt, Katrin Gobat, Silke Gillessen, Richard Cathomas
Journal: Journal of Clinical Oncology (2025)

TPS280 Background: The implementation of androgen-receptor pathway inhibitors (ARPI) +/- docetaxel (doce) in addition to androgen deprivation therapy (ADT)in metastatic hormone sensitive prostate cancer (mHSPC) has limited the therapeutic options in the mCRPC setting. In the SAKK 08/16 trial, darolutamide (daro) maintenance demonstrated prolonged radiographic progression-free survival (rPFS) compared to placebo in patients (pts) with mCRPC who had received prior ARPI, and did not progress during taxane therapy. This benefit was more pronounced in pts with a response to the prior ARPI. Continuing enzalutamide in addition to doce versus a switch to doce alone after progression on enzalutamide in later line mCRPC has been demonstrated to prolong PFS in a phase 3 trial. The continued maximal androgen-receptor (AR) blockage in the mCRPC first-line setting in addition to a standard of care could potentially control persistent AR-pathway sensitive clones. Daro is an optimal drug for the use as ARPI maintenance because of its favourable safety profile and a low potential for drug-drug interactions.We hypothesize that the addition of daro to a first-line SOC in mCRPC in pts with a prior long response to ADT and ARPI in mHSPC improves rPFS. Methods: SAKK 08/23 is an international open-label randomized phase 2 trial enrolling pts with ECOG 0-2 having progressed to mCRPC with a response to prior ADT-ARPI combination for at least 18 months showing at least a 50% PSA response or partial remission according to RECIST. Pts must not have received treatment for mCRPC. Pretreatment with doce in mHSPC is allowed. Patients will be randomized 1:1 to receive physician’s choice standard of care (SOC: doce, cabazitaxel, 177 lutetium-PSMA, radium-223 or olaparib) or SOC with daro. Treatment with daro will be continued until progression according to PCWG3. Stratification factors include country and treatment with taxanes versus radium-223 versus 177 lutetium-PSMA vs olaparib. The primary endpoint is rPFS. Secondary endpoints include overall survival, time to symptomatic/clinical progression, event-free survival, time to PSA progression by PCWG3, objective response rate according to RECIST, PSA response and PSA response duration. Without daro we expect a median rPFS of 6 months for taxanes, radium-223 and Olaparib and 8 months for 177 lutetium-PSMA. Assuming a three months increase in median rPFS with the addition of daro 121 events are needed (one-sided type I error of 10%, power of 80%) which leads to a sample size of 162 patients (including 10% dropout after one year). The trial will enroll pts in Switzerland and Spain. Accrual to the study is currently ongoing. Clinical trial information: NCT06401980 .
Bayesian re-analysis: Comparing radical cystectomy with trimodality therapy in patients with muscle invasive bladder cancer.
Authors: Abigail Pepin, Ronac Mamtani, John Paul Christodouleas, Daniel Lee
Journal: Journal of Clinical Oncology (2025)

737 Background: Randomized trials comparing radical cystectomy (RC) and trimodality therapy (TMT) in muscle invasive bladder cancer (MIBC) have not been feasible. In 2023, Zlotta et al. published a retrospective multi-institutional analysis evaluating metastasis free survival (MFS) and overall survival (OS) outcomes in patients treated with RC or TMT. Zlotta et al. is generally considered the highest quality data available for this comparison, but the results were presented using traditional frequentist statistics which can be challenging to interpret. The purpose of this study was to use Bayesian re-analysis of Zlotta et al. to convert its frequentist summary statistics into outcome probabilities, enabling a more intuitive treatment comparison between RC and TMT. Methods: The Zlotta et al. study results comparing RC and TMT were described by estimating the probability of any benefit (HR&lt;1) or a minimal clinically meaningful (MCR) benefit (HR&lt;0.8). An informative neutral prior distribution was defined by surveying bladder cancer experts on the comparison of RC and TMT use in bladder cancer patients included in Zlotta et al. (cT2–T4N0M0, &lt;7cm, no or unilateral hydronephrosis, no CIS, average age 70). Using a neutral prior of no advantage to either treatment and methods adapted from Wijeysundera et al., we calculated probabilities of a benefit in MFS and OS. We performed sensitivity analyses by varying the strength of the study-specific priors’ neutrality assumption and by using an alternative informative neutral prior developed for oncology comparisons but not specifically for MIBC. Results: The expert-informed informative neutral prior assumption assumed a 70% chance that any differences with respect to any cancer control or overall survival outcome would be less than the minimal clinically significant thresholds. The posterior probabilities of the primary analysis are presented in the table. Sensitivity analyses of the estimates of any benefit for MFS and OS varied by up to 3%, while estimates of a MCR benefit for MFS and OS varied up to 15%. Conclusions: The best available evidence suggests that in selected MIBC patients there is a &gt;96% chance that TMT is associated with any OS advantage over RC but a &lt;59% chance that the benefit reaches a minimal clinically meaningful benefit threshold. There is &gt;65% chance that TMT is associated with any MFS advantage over RC but &lt;13% chance of a minimal clinically meaningful benefit. Bayesian re-analysis of outcome estimate from Zlotta et al. 2023. Probability of any benefit of TMT over RC (HR&lt;1) Probability of any benefit of RC over TMT (HR&gt;1) Probability of a MCR benefit of TMT over RC (HR&lt;0.8) Adjusted MFS Zlotta et al. Outcomes IPTS SHR 0.89 (95% CI 0·67–1·20) 73% 27% 12% PSM SHR 0.93 (95% CI 0.71–1.24) 66% 34% 7% Adjusted OS IPTS SHR 0.70(95% CI 0.53–0.92) 98% 2% 58% PSM SHR 0.75 (95% CI 0.58–0.97) 97% 3% 44%
Treatment strategies in human papillomavirus-related advanced penile cancer
Authors: Mattia Longoni, Christian D. Fankhauser, Fausto Negri, Andrea Salonia, Giuseppe Basile, Peter A. S. Johnstone, Marco Bandini, C. Fankhauser, M. Bandini, F. Castiglione, H. M. De Vries, G. Fallara, J. Lobo, K. H. Pang, A. Sachdeva, A. Thomas, I. Anselmo da Costa Santiago, L. Antonelli, G. Basile, W. Cazzaniga, J. Chorbińska, L. Elst, D. Glombik, J. B. Grogg, S. Nazzani, P. Paffenholz, A. Poterek, S. Yan, A. Territo
Journal: Nature Reviews Urology (2025)
Survival outcomes among metastatic castration-resistant prostate cancer patients treated with androgen receptor pathway inhibitor and docetaxel.
Authors: Yunji Hwang, Travis Wheeling, Mark Hatfield, Christopher Kim
Journal: Journal of Clinical Oncology (2025)

57 Background: Real-world evidence on treatment patterns and real-world overall survival (rwOS) are limited in metastatic castration-resistant prostate cancer (mCRPC) patients treated with prior androgen receptor pathway inhibitor (ARPI) and docetaxel treatment. The objective of the study was to describe distribution of ARPI switch or cabazitaxel and their rwOS in patients with mCRPC settings after ARPI and docetaxel treatment. Methods: The study analyzedConcertAI Patient 360 data with a prostate cancer diagnosis in US, derived from electronic health records and claims data between 1990 and 2023. Among the eligible adult mCRPC patients, the study population included patients who subsequently received ARPI switch or cabazitaxel in mCRPC setting. The patient number and distribution (%) by treatments and subgroups were summarized. The study used the Kaplan-Meier method to calculate rwOS (median, months; interquartile range, IQR) and rwOS rate (%) at 12, 24 and 36 months from the start date of ARPI switch or cabazitaxel (Index Date). Results: Among 945 mCRPC patients with prior ARPI and docetaxel treatment (median age: 72 years; white: 79%; baseline PSA ≥ 100 ng/mL: 41%), cabazitaxel was more commonly used (59%) compared to ARPI switch (abiraterone: 22%; enzalutamide: 19%). The rwOS was 13 months, and rwOS rates of the overall patients were 53%, 29% and 21% for at 12, 24 and 36 months, respectively. Patients with liver metastasis had 9 months of median rwOS, while patients without liver metastasis had 14 months. Conclusions: The relatively short OS demonstrated the unmet medical need in mCRPC patients who received multiple treatments including ARPI and taxane-based chemotherapy, warranting the development of more effective and innovative treatments extending patient survival. Overall survival in metastatic castration-resistant prostate cancer patients treated with androgen receptor pathway inhibitor and docetaxel. Total (N=945) Months (IQR) Median OS in total patients (Death, n=770; 81%) 13 (6 - 29) Median OS in subgroup patients by liver metastasis No 14 (6 - 30) Yes 9 (5 - 20) OS Rate % 12 months 53 24 months 29 36 months 21 IQR= interquartile range; OS=overall survival.
Trends and demographic disparities in the preferred place of death for bladder cancer patients in the United States (2000–2020): An analysis from the CDC database.
Authors: Manas Vaibhav Pustake, Mohammad Arfat Ganiyani, Atulya Aman Khosla, Avi Ravi Harisingani, Mostafa Eysha
Journal: Journal of Clinical Oncology (2025)

747 Background: Understanding trends in end-of-life care for bladder cancer patients, particularly their preferred place of death (PPOD), is essential for improving palliative care planning. Despite being a leading cause of mortality in the U.S., there is limited insight into how preferences for end-of-life settings have evolved over time, or how they vary across demographic groups. Identifying these trends can help enhance care quality and address disparities in access to hospice and home-based care. This study aims to provide a comprehensive analysis of PPOD trends for bladder cancer patients from 2000 to 2020. Methods: Data from the CDC WONDER database were used to analyze bladder cancer mortality trends between 2000 and 2020. Deaths were categorized by place of death (home, hospice, medical facility, nursing home), age, race, census region, and year. Descriptive statistics summarized mortality trends, and chi-square tests assessed associations between demographic characteristics and place of death. Logistic regression identified factors associated with hospice utilization, adjusting for age, race, and region. The analysis also examined the impact of the COVID-19 pandemic on end-of-life care in 2020. Results: Between 2000 and 2020, there were 293,906 bladder cancer deaths in the U.S., with the South accounting for the highest proportion (35.6%). Home was the most common place of death (41.6%), followed by medical facilities (24.4%), nursing homes (19.5%), and hospice facilities (9.0%). Significant associations were found between place of death and age, race, and region (p &lt; 0.001). Logistic regression showed younger individuals (under 85) had higher odds of dying in hospice, while Black individuals were less likely to use hospice than White individuals (OR = 0.699, p &lt; 0.001). Hospice utilization increased over time (OR = 1.134 per year, p &lt; 0.001). In 2020, home and hospice deaths increased, with a decline in medical facility deaths, likely due to the COVID-19 pandemic. Conclusions: Hospice care and home-based end-of-life care have become more prominent, though disparities in access persist, particularly among racial and regional groups. These findings highlight the need for more inclusive palliative care strategies to ensure equitable access to compassionate end-of-life care for all patients. Logistic regression results for factors influencing hospice utilization. Variable B S.E. p-value Odds Ratio 35-44 years -18.100 1742.864 0.992 0.000 45-54 years 0.309 0.041 &lt;0.001 1.362 55-64 years 0.291 0.023 &lt;0.001 1.338 65-74 years 0.207 0.018 &lt;0.001 1.230 75-84 years 0.121 0.017 &lt;0.001 1.128 Asian or Pacific Islander -19.165 946.130 0.984 0.000 Black or African American -0.358 0.031 &lt;0.001 0.699 Year (2000-2020) 0.126 0.001 &lt;0.001 1.134
The prognostic value of LDH in patients with good risk metastatic seminoma treated with single agent carboplatin AUC10.
Authors: Nasreen Abdul Aziz, Kenrick Ng, Sushila Ganguli, Prabhakar Rajan, Anand Sharma, Jonathan Shamash
Journal: Journal of Clinical Oncology (2025)

644 Background: Raised lactate dehydrogenase (LDH) is a surrogate marker for disease burden and an independent adverse prognostic factor for IGCCCG good risk metastatic seminoma patients treated with cisplatin and etoposide-based chemotherapy (Beyer et al, 2021). Patients with a pre-treatment LDH greater than 2.5x the upper limit of normal (ULN), despite still categorized as good risk disease, have a poorer 3-year progression free survival (PFS) of 80% with this combination treatment. Carboplatin Area Under the Curve (AUC) 10 monotherapy is an alternative to cisplatin and etoposide-based chemotherapy, with comparable effectiveness and a better side effect profile. However, the prognostic value of LDH and specific outcomes of patients with raised LDH in patients treated with carboplatin AUC10 has not been evaluated. Methods: A retrospective analysis of outcomes of good risk metastatic seminoma patients treated with carboplatin AUC10 from January 2000 to January 2021 at two supra-regional cancer centres was conducted. Data were extracted using electronic health records. The variables collected included primary tumor location, stage, tumor markers, relapse date, post-relapse treatment and cause of death. Results: 245 patients were identified with a median follow up period of 5.9 years. The primary site of the tumor was most commonly the testes (n=229, 93.5%). 76 (31%) presented with stage 2a, 81 (33%) with stage 2b and 43 (16%) with stage 2c. 14 patients (6%) experienced a relapse, with 11 patients received bleomycin, etoposide and cisplatin as salvage treatment. 24 patients (10%) had LDH levels &gt;2.5 ULN. The 3-year PFS rate for patients with LDH &gt;2.5 ULN was 79.2% versus 95% in LDH &lt;2.5 ULN (p=0.0004). This was comparable to the 80% reported in the high LDH group by Beyer et al. Conclusions: Our results confirm the validity of raised LDH as an adverse prognostic factor in good risk metastatic seminoma patients treated with carboplatin AUC10, with similar PFS outcomes compared to etoposide-cisplatin based chemotherapy described in Beyer et al. Elevated LDH does not appear to be a contraindication to the use of carboplatin AUC10 monotherapy in this patient population and represents a less toxic alternative to etoposide-cisplatin based chemotherapy.
A multi-centre review of the use of adjuvant pembrolizumab for renal cell carcinoma.
Authors: Eleanor McCarthy, Alice Chadwick, Juan Jose Soto-Castillo, Lisa M Pickering, Ricky Dylan Frazer, Manon Pillai, Tom Waddell, Duncan Lindsay, Ansh Agarwal, Diana Matthews, Mahrukh Khalid, Simon Aird Grumett, Ellis Adamson, John McGrane, Helen Clare Dearden, Naveen Vasudev, Natalie Charnley
Journal: Journal of Clinical Oncology (2025)

484 Background: In patients with increased risk of recurrence after surgical resection of renal cell carcinoma (RCC), adjuvant treatment with pembrolizumab has been shown to reduce recurrences and improve overall survival. This treatment is now offered as standard of care in England. In the KEYNOTE 564 trial 96.3% of patients who received pembrolizumab experienced at least one adverse event and 32.4% of patients experienced an adverse event of grade 3-5. 38.9% of trial patients discontinued treatment early; 21.3% due to adverse events and 10.5% due to disease recurrence. 7.4% of patients who were treated with pembrolizumab were treated with high dose systemic steroids (≥40mg prednisolone per day). Aims: To evaluate how real world data compares to the findings of KEYNOTE 564, in UK centres. Methods: This was a retrospective review of 182 patients treated with adjuvant pembrolizumab following surgery for RCC across 7 centres in the UK between 2022-2024. Toxicity, discontinuation, use of steroids, and recurrences were assessed. Results: 182 patients were started on adjuvant pembrolizumabbetween 2022-2024. Median FU is 8.4 months. Overall, 18 patients (9.9%) have experienced recurrence, and 15 (83.3%) of these occurred during treatment. 82 (45.1%) patients are currently undergoing treatment, and 41 (22.5%) patients completed the full 12-month course. 59 (32.4%) patients did not complete the full course, 44 (24.1%) due to toxicity and 15 (8.2%) due to recurrence. Mean number of cycles completed for patients discontinuing treatment was 3.4 (range 1 – 8). Toxicity was varied with endocrine (24%), skin (23%) &amp; colitis (12%) being the most common toxicities of all grades. 24 (13.2%) and 3 (1.6%) patients experienced grade 3 and grade 4 toxicities respectively. The commonest toxicity leading to treatment discontinuation was colitis (27.3%). The number of patients requiring steroids for toxicity management was 59 (32.4%) with 34 (18.6%) requiring high dose steroids and 7 (3.8%) requiring additional immunosuppressive agents (methotrexate (3), infliximab (3) and MMF (1)). 26 (14.2%) patients required hospitalisation for management of toxicity. There was 1 treatment-related death due to complications from colitis and nephritis. Conclusions: In our group of patients, discontinuations of Pembrolizumab due to toxicity and recurrence rates were similar to data from KEYNOTE 564. A larger proportion of patients in our real world data were treated with high dose steroids (19%) compared to the trial (7.4%).