Circulating tumor DNA fraction (ctDNA%) to independently predict for clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5049-5049
Author(s):  
Corinne Maurice-Dror ◽  
Nicolette Fonseca ◽  
Cameron Herberts ◽  
William Fan ◽  
Alexander W. Wyatt ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Prognostic Information ◽  
Kaplan Meier ◽  
Treatment Naïve ◽  
Ecog Ps

5049 Background: CtDNA% (the tumour-derived proportion of cell-free DNA (cfDNA)) is abundant in >60% of mCRPC pts and associates with adverse clinical prognostic factors. However, prognostic associations have not been comprehensively tested across clinical contexts. We evaluated the utility of ctDNA% as an independent prognostic biomarker in patients with mCRPC prior to first-line (1L) therapy. Methods: 410 treatment-naïve mCRPC pts had blood samples drawn prior to 1L therapy and followed prospectively for outcomes. Plasma cfDNA was subjected to deep targeted sequencing and ctDNA% was calculated using validated methods ( Annala, Cancer Discov, 2018 ). Overall survival (OS), PSA progression free survival (PSA PFS) and PSA declines ≥50% from baseline (PSA50 response rate (RR)) were stratified by ctDNA% and compared using Kaplan-Meier and Cox proportional hazards analysis. Results: Median age was 73 yrs. (range 45-98), the majority of pts had ECOG PS 0-1 (78%) and 9.5% had liver metastases at baseline. The most common 1L therapy employed was androgen receptor pathway inhibitors (90%). Median follow-up was 21 mo. (range 1-75) and median ctDNA% was 4.9% (range: 0-89%). Stratifying patients into high ctDNA (>30%) and Low ctDNA (≤2%) groups showed stronger association with OS and PSA PFS than grouping by median (Table). In a univariate comparison to pts with low ctDNA (≤2%), pts with high ctDNA% (>30%) had significantly shorter median PSA PFS, median OS and a lower PSA50 RR (Table). In a multivariable adjustment for clinical prognostic factors and cfDNA concentration, high ctDNA% remained strongly associated with OS (HR= 3.3, 95%CI: 2.1-5.3, p<0.001) and PSA PFS (HR: 3.7, 95%CI: 2.4-5.9, p<0.001). Although ctDNA% and total cfDNA concentration were correlated (R2=0.55), association with OS was stronger for ctDNA% than cfDNA concentration (stratified at median; HR: 2.9 (2.3-3.7), p<0.001 vs HR: 2.1 (1.7-2.6), p<0.001). Conclusions: In a large cohort of treatment-naïve mCRPC pts, ctDNA% prior to 1L treatment provided strong prognostic information independent of known clinical factors. These data further demonstrate the multipronged clinical utility of ctDNA-based profiling for actionable genomic alterations.[Table: see text]

Predictors for detecting circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 634-634
Author(s):  
Allan Andresson Lima Pereira ◽  
Jonathan M. Loree ◽  
Jennifer S Davis ◽  
Michael Lam ◽  
Van Karlyle Morris ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Clinical Laboratory ◽  
Binary Logistic Regression ◽  
Disease Status ◽  
Circulating Tumor Dna ◽  
Cox Proportional Hazards ◽  
Prognostic Information ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Gene Assay

634 Background: Utilization of ctDNA has been rapidly adopted as a predictive diagnostic in advanced NSCLC and indications in GI cancers may be emerging. While tissue-based assays have yields above 90%, there is less known about factors that influence the sensitivity of ctDNA for detecting mutations. Methods: We retrospectively evaluated mCRC patients (pts) who had plasma-derived NGS utilizing a highly-sensitive 68-73-gene assay. Tissue from prior resections or biopsies underwent concurrent 46-gene sequencing. In a case-control design, pts with a known mutation on tissue and radiologic evidence of metastatic disease but no detectable ctDNA mutation were matched 1:3 with randomly selected pts with detectable mutations and compared according to clinical, laboratory, and radiologic characteristics. A binary logistic regression was performed and Kaplan-Meier and Cox-proportional hazards models were used to compare overall (OS) and progression-free (PFS) survivals. Results: Of 427 mCRC pts who underwent ctDNA testing, 416 pts met inclusion criteria. Plasma-derived NGS did not find tumor mutations in 66 cases (15.9%); 198 pts with detectable alterations were selected as controls. After multivariate analysis, the lack of detection of ctDNA was associated with decreasing age (OR 0.94; 95%CI 0.91-0.98; p = 0.004), absence of liver (OR 0.19; 95%CI 0.08-0.45; p < 0.001) and lymph node metastases (OR 0.28; 95%CI 0.12-0.70; p = 0.006). A key determinant was timing of collection relative to disease status: plasma collected after evidence of progression was substantially more likely to have detectable alterations (OR 10.95; 95%CI 4.23-28.33; p < .001); in these pts, the modeled rate of detection was 98%, which increased to > 99% if the pts also had either liver or nodal disease. Pts with no detectable ctDNA had better OS (HR 0.38; 95%CI 0.21-0.69, p = 0.002) and PFS (HR 0.52; 95%CI 0.32-0.85; p = 0.009). Conclusions: When limited to ctDNA collected in newly diagnosed or recently progressing pts, the yield of ctDNA is 98%, which equals or exceeds the yield of tissue based testing. Our findings support the notion that ctDNA testing, when appropriately utilized, can replace tissue based testing and may provide prognostic information.

Sunitinib in patients with pancreatic neuroendocrine tumors (panNETs): Exploratory pharmacogenomic analyses.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 255-255
Author(s):  
Nicola Fazio ◽  
Jean-Francois Martini ◽  
Adina-Emilia Croitoru ◽  
Michael Schenker ◽  
Sherry Li ◽  
...  
Keyword(s):  
Protein Transport ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nucleotide Polymorphisms ◽  
Exact Test ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve

255 Background: In a phase IV trial (NCT01525550), median progression-free survival (PFS) was 13.2 mo in sunitinib-treated patients (pts) with well-differentiated panNETs. Objective response rate (ORR) was 24.5% and median overall survival (OS) was 37.8 mo. Exploratory analyses evaluated potential associations between single nucleotide polymorphisms (SNP) in genes involved in angiogenesis, protein transport or inflammatory response and clinical outcomes. Methods: Blood samples were genotyped using TaqMan assays for 12 SNPs previously associated with panNET risk, prognosis or drug effect. Associations between SNP and PFS or OS were assessed by comparing genotypes within treatment-naïve (TN), previously treated (PT) and combined groups, and within a genotype between treatment groups, using Kaplan-Meier analysis and Cox proportional hazards models. Fisher’s exact test was used for association between ORR and genotype. PFS and ORR were investigator-assessed. P values displayed are unadjusted and Bonferroni method was used for multiplicity adjustment. Results: 56 pts were genotyped: 25 TN and 31 PT. There were no significant associations between genotype and PFS or OS but there was a trend toward shorter PFS in pts with VEGFR1 rs9554320 C/A versus C/C (hazard ratio [HR] 1.78; 95% confidence interval [CI] 0.83–3.82; p = 0.117) and VEGFR1 rs9582036 A/C versus A/A (HR 1.88; 95% CI 0.9–3.93; p = 0.102). The genotypes G/G of VEGFA rs2010963 (p = 0.041) , G/G of VEGFA rs833068 (p = 0.041) and A/C of VEGFR1 rs9582036 (p = 0.046) showed a trend toward a higher ORR in the PT versus TN group. Genotype T/T of VEGFR2 rs7692791 (p = 0.103) showed a trend toward to a lower ORR in the TN versus PT group. Higher ORR was associated with IL1B rs16944 G/A versus G/G (46.4% vs 4.5%; p = 0.001) in the combined group. Conclusions: Potential associations between ORR and VEGFA rs2010963 and rs833068, VEGFR1 rs9582036 and VEGFR2 rs7692791 were observed. IL1B rs16944 was significantly associated with ORR, consistent with the role of IL1B in panNET etiology and development. Most correlations were not significant after adjustment for multiplicity. Clinical trial information: NCT01525550.

Outcomes of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with pazopanib after progression on other targeted therapies (TT): A single-institution experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4615-4615
Author(s):  
Marc Ryan Matrana ◽  
Aditya V. Shetty ◽  
Bradley J. Atkinson ◽  
Lianchun Xiao ◽  
Paul G. Corn ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Kinase Inhibitor ◽  
Multivariable Analysis ◽  
Safety Data ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve ◽  
Metastatic Sites

4615 Background: Pazopanib is an approved multi-tyrosine kinase inhibitor that prolongs progression-free survival (PFS) compared to placebo in treatment-naive and cytokine-refractory mRCC. Outcomes and safety data on its use after TT are limited. Methods: We retrospectively reviewed pts with mRCC who received salvage pazopanib between 11/09-11/11. Kaplan-Meier method was used to estimate survival outcomes. PFS was calculated from start of pazopanib until progressive disease (PD) or death. Univariable and multivariable Cox proportional hazards models were fitted to evaluate associations of PFS with covariables. Results: 114 consecutive pts met inclusion criteria (median age 62.6 years, 66% males, 83% clear cell). All pts had PD after other TT (median # of prior TT 2, range 1-5; median time on prior TT 23.3 mos). 79% of pts had PD on sunitinib, 39% on sorafenib, 19% on temsirolimus, 59% on everolimus, and 23% on bevacizumab. 25% received prior chemotherapy and 16% received prior cytokines in addition to TT. 87% had prior nephrectomy. 11% had favorable-risk, 68% intermediate-risk, and 21% poor-risk per MSKCC criteria. 85 events (PD or death) occurred. Median OS was 17 mos (95% CI: 10.3-NA). Median PFS was 6.4 mos (95% CI: 4.5-9.5). By multivariable analysis, PFS was associated with male gender (HR=0.433, 95%CI: 0.269-0.696; p=0.0006), # of metastatic sites (HR=1.252; 95%CI: 1.04-1.503; p=0.016), hypertension exacerbation (HR=0.378; CI: 0.175-0.813; p=0.0128) and PS 2+ vs.0-1 (HR=2.067; CI: 1.243-3.437; p=0.0052). 58% discontinued pazopanib due to PD, 12% died of PD on treatment, and 11% discontinued pazopanib due to adverse events (AEs), mostly GI complaints or fatigue. There were no treatment related deaths. Common AEs included: fatigue (44%), diarrhea (29%), nausea/vomiting (15%), anorexia (14%), hypertension exacerbation (11%), hypothyroidism (11%), hand-foot skin reaction (9%), and increase LFTs (4%). 86% of AEs were grade 1/2. Conclusions: In this retrospective study, pazopanib demonstrated efficacy in mRCC following PD with other TT. AEs were mild/moderate and manageable.

Conditional survival probability of patients with resected pancreatic adenocarcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 284-284
Author(s):  
Mark Vikas Mishra ◽  
Colin Eamon Champ ◽  
Timothy Norman Showalter ◽  
Scott W. Keith ◽  
Pramila R. Anne ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Pancreatic Adenocarcinoma ◽  
Proportional Hazards ◽  
Female Gender ◽  
Cox Proportional Hazards ◽  
Conditional Survival ◽  
Prognostic Information ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Younger Age

284 Background: The purpose of this study is to evaluate conditional survival (CS) probabilities for patients with resected pancreatic adenocarcinoma (PC) amongst patients who have survived ≥1 more year(s) after diagnosis. Methods: Patients with resected PC from 1998-2008 were identified from the Surveillance, Epidemiology and End Results Database. Data on patient, tumor and treatment characteristics were extracted. Overall survival (OS) rates were calculated using the Kaplan-Meier method. A multivariate analysis (MVA) at different time points from survival was performed to determine independent prognostic factors associated with all-cause mortality hazard ratios (HRs) using Cox proportional hazards models. Results: A total of 4,883 patients with resected PC were identified. Fourteen percent of patients had Stage IA/B disease, 23% Stage IIA, 53% Stage IIB, and 2% Stage IIIA, and 6% with unknown stage. The 1-, 3-, and 5-year survival estimates for patients at diagnosis were 67%, 29%, and 21%, respectively. One, 3- and 5-year survival probabilities conditional upon number of years already survived are shown in table 1. Prognostic factors significantly correlated with improved OS at the time of diagnosis on MVA include: earlier stage, younger age, later year of diagnosis, white race, female gender, and residence in a high income district (p < 0.05). After already surviving 3 years following diagnosis, younger age was the only prognostic factor correlated with improved OS (p<0.05). Conclusions: CS estimates provide additional prognostic information that may be used to counsel PC patients on how their prognosis may change over time. Further research utilizing prospectively-collected data is warranted to help determine recommended follow-up intervals and benchmarks for future clinical trials. [Table: see text]

RADT-33. LONG-TERM OUTCOMES, TREATMENT UTILIZATION, AND PROGNOSTIC FACTORS FOR PEDIATRIC CHORDOMA: AN NCDB ANALYSIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi48-vi48
Author(s):  
James Cantrell ◽  
Pawan Acharya ◽  
Sara Vesely ◽  
Michael Confer ◽  
Ozer Algan ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Radiation Dose ◽  
Proportional Hazards ◽  
Propensity Score Analysis ◽  
Descriptive Analysis ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Total Resection ◽  
Kaplan Meier

Abstract BACKGROUND Chordomas are rare tumors arising from the embryonal notochord presenting at the base of skull, spine, or sacrum. Pediatric chordomas (PC) comprise less than 5% of all chordomas and are more likely to be atypical or dedifferentiated. Evidence for management is limited to single institution series with 5-year overall survival (OS) between 60-100%. METHODS Using the NCDB Participant User File, a retrospective observational cohort study was performed. The cohort was defined using the bone-soft-tissue, brain, and central nervous system databases selecting for cases with chordoma ICD-03 codes and age ≤ 25 years. Kaplan Meier method, log-rank test, and Cox proportional hazards regression were performed. RESULTS 297 patients from 2004-2017 met inclusion criteria for descriptive analysis with 269 cases included for survival analysis. Mean age was 16.9 years, with 10% less than age 5. The cohort was 55% female, 8% Black, and 79% White. Primary sites included bones of the skull (70%), spine (22%), and pelvis (6%). Regarding treatment, 7% had no resection, 49% sub-total resection (STR), 33% gross-total resection (GTR), and 11% unspecified resection. 51% received radiation therapy with 46% of those receiving proton therapy. 7% received chemotherapy. The 1, 3, 5, and 10-year OS was 95%, 86%, 77%, and 72%. Selected prognostic factors from univariable OS model for OS analysis included: age &gt; 5 (HR 0.30 (95% CI 0.16-0.57) p = 0.0002), surgical resection [GTR (HR 0.28 (95% CI 0.12-0.63) p = 0.0023) and STR (HR 0.27 (95% CI 0.12-0.59) p = 0.0011)], and radiation dose ≥ 7200cGy (HR 0.40 (95% CI 0.16-0.99) p = 0.047). CONCLUSION In the largest cohort reported for PC, 3 and 10-year OS was 86% and 72%. Age, surgery, and radiation dose are important prognostic factors. Propensity score analysis to gauge effect of treatment, tumor, and patient characteristics on OS is forthcoming.

scholarly journals Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Kyle W Singleton ◽  
Alyx B Porter ◽  
Leland S Hu ◽  
Sandra K Johnston ◽  
Kamila M Bond ◽  
...  
Keyword(s):  
Treatment Response ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Response To Therapy ◽  
Cytotoxic Therapy ◽  
Kaplan Meier ◽  
Recurrent Gbm

Abstract Background Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. Methods DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. Conclusion DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

scholarly journals Efficacy and safety of selective internal radiation therapy with yttrium-90 for the treatment of unresectable hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nguyen Van Thai ◽  
Nguyen Tien Thinh ◽  
Thai Doan Ky ◽  
Mai Hong Bang ◽  
Dinh Truong Giang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
Tumor Response ◽  
Complete Response ◽  
Tumor Burden ◽  
Cox Proportional Hazards ◽  
Factors Affecting ◽  
Kaplan Meier ◽  
Modified Recist

Abstract Background This retrospective analysis was undertaken to evaluate the efficiency of SIRT with Y-90 microspheres and determined prognostic factors affecting patients with unresectable HCC. Methods A total of 97 patients diagnosed with unresectable HCC who underwent SIRT with Y-90 microspheres. Patient survival was assessed using the Kaplan–Meier method, and prognostic factors affecting survival were assessed using log-rank tests and Cox proportional hazards regression. Results Among the 97 patients (90 males, mean age 60.4 ± 12.3 years) who underwent SIRT, the median clinical follow-up was 16.4 (1.8–62) months. The median overall survival (OS) was 23.9 ± 2.4 months. Tumor response according to the Modified RECIST in patients followed up beyond 6 months included a complete response (CR) to treatment in 12 patients (18.8%), partial response (PR) in 23 (35.8%), stable disease (SD) in 8 (12.5%), and progressive disease (PD) in 21 (32.8%). Factors associated with longer OS included age > 65 years, BCLC stage B, tumor size < 5 cm, tumor burden < 25%, and tumor response (CR/PR). In multivariate analysis, unilobar disease and objective tumor response (CR/PR) were predictors of longer OS. Conclusion SIRT was an effective treatment for unresectable HCC. Unilobar disease before SIRT and tumor response (CR/PR) were positive prognostic factors.

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

Results of subset analyses on overall survival (OS) from study CA184-043: Ipilimumab (Ipi) versus placebo (Pbo) in post-docetaxel metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Charles G. Drake ◽  
Eugene D. Kwon ◽  
Karim Fizazi ◽  
Alberto Bossi ◽  
Alfons JM van den Eertwegh ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Prognostic Features ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
To Receive ◽  
Clinical Trial Information

2 Background: The CA184-043 phase 3 study did not reach statistical significance for its primary endpoint of OS (HR=0.85, p=0.053). However, antitumor activity was observed in other efficacy endpoints, including progression-free survival. Prespecified subset analyses were performed to understand if any prognostic features may identify mCRPC patients (pts) more likely to benefit from Ipi treatment. Methods: 799 pts were randomized to receive a single dose of radiotherapy (RT) followed by either Ipi (N=399) or Pbo (N=400). Prespecified subset analyses based on Kaplan-Meier/Cox methodology were performed using known prognostic factors for OS in mCRPC. Results: Prespecified subset analyses suggested that Ipi may be more active in pts with favorable prognostic factors, including no visceral disease, alkaline phosphatase <1.5 ULN, and hemoglobin ≥11 g/dL (Table). The safety profile in this study was consistent with previous reports of Ipi. Conclusions: Based on these subset analyses, Ipi added to RT appears to have greater activity than RT alone in pts with a favorable prognostic profile. These results support continued investigation of Ipi in the ongoing CA184-095 study in chemotherapy-naive mCRPC pts. Clinical trial information: NCT00861614. [Table: see text]

Histologic subtype and response to immune checkpoint inhibitor (ICI) therapy in advanced urothelial cancer (aUC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 495-495
Author(s):  
Natalie J. Miller ◽  
Ali Raza Khaki ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Mehmet Asim Bilen ◽  
Victor Sacristan Santos ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Routine Practice ◽  
Histologic Subtype ◽  
Tract Cancer ◽  
Kaplan Meier ◽  
Urinary Tract Cancer ◽  
Tract Disease ◽  
Histologic Types

495 Background: Urinary tract cancer can be pure urothelial carcinoma (PUC) or variant UC (VUC, defined here as pure non-UC or mixed UC + non-UC); VUC often has a worse prognosis. Little is known about outcomes for patients (pts) with VUC receiving ICI. We hypothesized that VUC does not compromise ICI efficacy in pts with aUC. Methods: We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathologic, treatment and outcomes data was collected for pts with aUC who received ICI. Pts were stratified to PUC vs VUC; VUC was further divided by histologic subtype, i.e. squamous, neuroendocrine (NE), etc. We compared overall response rate (ORR) using logistic regression, progression free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox proportional hazards; p<0.05 was significant. Results: 519 consecutive pts were identified; 405, 414 and 411 included in ORR, OS and PFS analyses, respectively. Demographics included mean age 69, 27% female, 66% ever smokers, 15% upper tract disease, 54% with extirpative surgery. ORR to ICI between pts with PUC and VUC was comparable (both 28%, p=0.86) without significant differences for individual subtypes vs PUC. Median OS for pts with PUC was 11.0 vs 9.9 mo for VUC (p=0.45), but only 3.7 mo for those with NE features (HR=3.01 [95% CI 1.63-5.57] vs PUC, p<0.001). Median PFS was 4.1 vs 5.2 mo for PUC vs VUC (p=0.46) and 2.8 mo for NE (HR=1.85 [95% CI 0.94-3.61] vs PUC, p=0.07). Conclusions: ORR to ICI and OS were comparable across histologic types; however, OS was shorter for tumors with NE features. VUC should not exclude pts from receiving ICI in routine practice and clinical trials.[Table: see text]

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