A phase III randomized intergroup trial (S0016) comparing CHOP plus rituximab with CHOP plus iodine-131-tositumomab for front-line treatment of follicular lymphoma: Results of subset analyses and a comparison of prognostic models.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8001-8001
Author(s):  
Oliver W. Press ◽  
Joseph M Unger ◽  
Michael Leo LeBlanc ◽  
Lisa M. Rimsza ◽  
Jonathan W. Friedberg ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Prognostic Models ◽  
Prognostic Impact ◽  
Prior Therapy ◽  
Follicular Lymphomas

8001 Background: Advanced follicular lymphomas (FL) are considered incurable with chemotherapy and there is no consensus on the best treatment. Outcomes are variable, but can be partially predicted by defined prognostic factors. SWOG and CALGB compared the safety and efficacy of 2 immunochemotherapy regimens in a Phase III trial enrolling 554 patients between 3/1/2001 and 9/15/2008. Methods: Patients were eligible if they had bulky stage II, III or IV FL and had not received prior therapy. Patients randomized to CHOP-R received 6 cycles of CHOP every 21 days + 6 doses of rituximab. Patients randomized to CHOP-RIT received 6 cycles of CHOP, followed by consolidative radioimmunotherapy with tositumomab/iodine I-131 tositumomab. A Cox proportional hazards multi-variable regression analysis assessed the prognostic impact of age, stage, LDH, LN size and number, performance status, hemoglobin, β2 microglobulin, BM involvement, and B symptoms.  The prognostic value of 3 multi-variable models were compared. Results: Outcomes were outstanding with either CHOP-R or CHOP-RIT (2 yr PFS: 76% vs 80% [ p =0.11]; 2 yr OS: 97% vs 93% [p =0.08], respectively).  Subset analyses so far have not identified any subgroups clearly benefitting to a greater degree from CHOP-R or CHOP-RIT in terms of both PFS and OS. Cox multivariable regression analysis identified serum-β2M, LDH level, and FLIPI index as the strongest prognostic factors associated with worse PFS and OS. Conclusions: Both regimens produced outstanding PFS and OS, and no statistically significant differences between them were observed.  FLIPI, FLIPI2, and LDH + β2M models were all strong predictors of patient outcomes.  A combination of LDH + β2M was as good as the FLIPI index, and was simpler to apply.  (Supported in part by NCI grants CA32102 and CA38926 from the NCI and GlaxoSmithKline.) [Table: see text]

Improved prognostic classification of patients receiving salvage systemic therapy for advanced urothelial carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 311-311 ◽  
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Jonathan E. Rosenberg ◽  
Dean F. Bajorin ◽  
Ashley Marie Regazzi ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Systemic Therapy ◽  
Proportional Hazards ◽  
Performance Status ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Phase Ii Trials ◽  
Advanced Urothelial Carcinoma

311 Background: Previously identified prognostic factors in patients (pts) receiving salvage systemic therapy for advanced urothelial carcinoma (UC) include performance status (PS), liver metastasis (LM), hemoglobin (Hb) and time from prior chemotherapy (TFPC). Given the prognostic impact of peripheral blood neutrophils (N), lymphocytes (L), thrombocytes (T) and albumin (Alb) in other malignancies, we investigated their impact in the salvage setting of advanced UC. Methods: Phase II trials of salvage systemic therapy were utilized. Data on N, L, T and Alb were required in addition to TFPC, Hb, PS and LM status. N, L, T and Alb were categorized as normal, <lower limit of normal (LLN) and >upper limit of normal (ULN). Cox proportional hazards regression was used to evaluate their association with overall survival (OS). An optimal regression model was constructed using forward stepwise selection and risk groups defined using number of identified adverse risk factors. Trial was a stratification factor. Results: Data was obtained from 10 trials accruing 708 pts. Of these, 682 pts had available TFPC, Hb, PS and LM status, while 631, 554, 649 and 491 had N, L, T and Alb available. Median OS was 6.8 (95% CI: 6.0-7.0) months. Neutrophilia (N>ULN), thrombocytosis (T>ULN) and hypoalbuminemia (Alb <LLN) were significant poor prognostic factors for OS on univariate analyses. After adjustment for TFPC <3 months, Hb <10 g/dl, PS >0 and LM status, only thrombocytosis and hypoalbuminemia remained significant (Table). Risk groups were constructed. Median OS was 8.8, 6.3, 5.0 and 3.8 months for n=290, 220, 123 and 49 patients with 0-1, 2, 3 and ≥4 factors. This 6-factor prognostic model was internally validated with an improvement in the c-index from 0.564 to 0.590. Conclusions: The addition of hypoalbuminemia and thrombocytosis to TFPC, Hb, PS and LM status enhanced the prognostic risk groupings in pts receiving salvage systemic therapy for advanced UC. [Table: see text]

Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 507-507 ◽  
Author(s):  
Kimmie Ng ◽  
Alan P. Venook ◽  
Kaori Sato ◽  
Bruce W. Hollis ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Blood Draw ◽  
Ecog Performance Status

507 Background: Prospective epidemiologic data suggest that higher levels of 25-hydroxyvitamin D [25(OH)D] are associated with improved survival in patients with colorectal cancer (CRC), however, the relationship between 25(OH)D and outcome in metastatic CRC, specifically, is unknown. Methods: We prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated metastatic CRC patients enrolled in CALGB 80405, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS WT amendment. Progression-free survival (PFS) was a secondary endpoint. Plasma 25(OH)D levels were measured at baseline by radioimmunoassay, and dietary and lifestyle behaviors collected from self-administered questionnaires. Cox proportional hazards models were used to calculate hazard ratios adjusted for other prognostic factors. In sensitivity analyses, patients who died within 3 or 6 months of blood draw were excluded to address the possibility of reverse causation. Results: Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL (range 2.2-72.7). Older and black patients, those with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (vs. 0), higher body-mass index, lower physical activity, and blood draws during the winter and spring had significantly lower levels of 25(OH)D. Patients in the highest quintile of 25(OH)D had significantly improved OS compared to those in the lowest after adjusting for pathologic and clinical prognostic factors (median 32.6 vs. 24.5 months; HR 0.67, 95% CI, 0.53-0.86; p trend 0.002). Increasing concentrations of 25(OH)D were also associated with improved PFS (median 12.2 vs. 10.1 months; HR 0.80, 95% CI, 0.64-1.01; p trend = 0.02). The results were consistent across subgroups of patient characteristics, including KRAS status, and remained unchanged after excluding patients who died within 3 or 6 months of blood draw. Conclusions: Higher concentrations of plasma 25(OH)D are associated with significantly improved survival in metastatic CRC patients treated with chemotherapy + biologics. Randomized trials of vitamin D supplementation are warranted and are currently underway.

Body weight loss (BWL) as a prognostic/predictive factor in previously treated patients (pts) with metastatic gastric or gastroesophageal junction cancer (mGC/GEJC): Post-hoc analyses of the phase III tags trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 476-476
Author(s):  
Michele Ghidini ◽  
Howard S. Hochster ◽  
Toshihiko Doi ◽  
Eric Van Cutsem ◽  
Lukas Makris ◽  
...  
Keyword(s):  
Body Weight ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Cox Model ◽  
Gastroesophageal Junction ◽  
Body Weight Loss ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Body Weight Data ◽  
Grade 3

476 Background: Nutritional status is closely linked to cancer mortality, and BWL has been shown to be prognostic for survival in curative, first-, and second-line settings in mGC/GEJC. In the phase III TAGS trial, trifluridine/tipiracil (FTD/TPI) showed clinical benefit versus placebo (PBO) and manageable safety in pts with mGC/GEJC who had received ≥2 prior chemotherapy regimens. The association of early BWL with survival outcomes in TAGS was examined in retrospective analyses. Methods: The TAGS intent-to-treat (ITT) population was categorized into pts who experienced <3% or ≥3% BWL from the start of treatment until day 1 of cycle 2 (each cycle: 28 days). Overall survival (OS), and progression-free survival (PFS) were compared between subgroups within each treatment arm due to significant imbalances of early BWL between treatment arms. The effect of early BWL on OS was assessed by a univariate Cox proportional hazards (PH) model as well as a multivariate Cox PH model that adjusted for baseline prognostic factors identified in the original ITT analysis. Results: Body weight data were available for 451 of 507 (89%) pts in the study (n=304, FTD/TPI; n=147, PBO). In the FTD/TPI and PBO arms, respectively, 74% (224/304 pts) and 65% (95/147) experienced <3% BWL, whereas 26% (80/304) and 35% (52/147) experienced ≥3% BWL at the end of cycle 1. Pts with <3% BWL had longer OS than those with ≥3% BWL in both FTD/TPI (median [m] OS: 6.5 vs 4.9 months [mo]; hazard ratio [HR], 0.75; 95% CI, 0.55–1.02) and PBO arms (mOS: 6.0 vs 2.5 mo; HR, 0.32; 95% CI, 0.21–0.49). The PFS HR for pts with <3% BWL vs ≥3% BWL was 0.95 (95% CI, 0.71–1.25; mPFS, 2.1 vs 1.9 mo) in the FTD/TPI group and 0.49 (95% CI, 0.34–0.72; mPFS, 1.9 vs 1.7 mo) in the PBO group. In the pooled ITT population, the unadjusted HR for the <3% vs ≥3% BWL group calculated using a univariate Cox model was 0.58 (95% CI, 0.46–0.73), indicating a strong prognostic effect of early BWL. Results of multivariate analyses were consistent with univariate analyses and suggested that early BWL was both a prognostic ( P<0.0001) and predictive (interaction P=0.0003) factor for OS in pts with mGC/GEJC. Grade ≥3 adverse events (AEs) of any cause were reported in 77% and 82% of FTD/TPI-treated pts in the <3% and ≥3% BWL subgroups, respectively, and in 45% and 67% of placebo-treated pts in the <3% and ≥3% BWL subgroups. Conclusions: To our knowledge, this is the first analysis to show that BWL is negatively associated with survival in pts with mGC/GEJC receiving third- or later-line treatment. In TAGS, early BWL (≥3% BWL at the end of cycle 1) was a strong negative prognostic factor for OS regardless of FTD/TPI or PBO treatment. Grade ≥3 AE frequencies were similar in FTD/TPI-treated pts with <3% or ≥3% BWL. The relationship of BWL to other prognostic factors will be explored further. Clinical trial information: NCT02500043.

Toxicity and efficacy of bolus (BOL) versus continuous intravenous (CIV) dosing of doxorubicin (DOX) in soft tissue sarcoma (STS): Post hoc analysis of a prospective randomized trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11023-11023
Author(s):  
Lee D. Cranmer ◽  
Yao Lu ◽  
Karla V. Ballman ◽  
Elizabeth Trice Loggers ◽  
Seth Pollack
Keyword(s):  
Randomized Trial ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Post Hoc Analysis ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Post Hoc

11023 Background: DOX remains critical in STS treatment. Controversy exists regarding its optimal administration route (BOL vs CIV). BOL vs CIV could affect toxicity and/or efficacy. A randomized trial to assess this is unlikely. We conducted a post hoc analysis to explore differences in these routes of DOX administration. Methods: Data from a prospective randomized phase III study of doxorubicin with or without evofosfamide (TH-302) were used. At the discretion of treating physician, BOL or CIV DOX could be used. Grade 3-5 hematologic, non-hematologic and cardiac toxicities and treatment response were explored using multivariable logistic regression. OS and PFS were analyzed using Kaplan-Meier and Cox proportional hazards. Results: 640 subjects were enrolled (556 BOL, 84 CIV). Baseline differences in age, extent of disease and prior radiotherapy were controlled for in regression models. Hematologic toxicity was associated with age, performance status (PS) and cumulative (CUM) DOX dose. Non-hematologic toxicity was associated with age, PS, receipt of prior radiotherapy and CUM TH-302 dose. Cardiac toxicity was only associated with CUM DOX dose. Odds of response were strongly associated with CUM DOX dose (mg/m2, OR = 1.011, p < 0.0001), and, to a lesser extent, with CUM TH-302 dose (g/m2, OR = 1.081, p = 0.0008), STS subtype and prior radiotherapy. Comparing CIV to BOL DOX, neither OS (median 21.7m vs 18.3m, HR = 0.85, p = 0.29) nor PFS (median 6.1m vs. 6.1m, HR = 0.89, p = 0.43) was affected by manner of DOX administration (CIV vs BOL). Cox analyses indicated that factors reflecting tumoral biology and host status, rather than treatment received, were associated with OS (PS, histologic STS subtype, histologic grade, receipt of prior radiotherapy) and PFS (PS, treatment-related toxicity). Conclusions: Our analyses provide no evidence for superiority of either BOL or CIV administration of DOX as regards toxicity or efficacy in STS treatment. Thus, the logistically simpler BOL administration of DOX should be favored over CIV administration.

Comparison of outcomes with pembrolizumab monotherapy (P) versus combination with chemotherapy (P+C) in advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21579-e21579
Author(s):  
Kartik Sehgal ◽  
Ritu R. Gill ◽  
Poorva Bindal ◽  
Anita Geevarghese Koshy ◽  
Danielle C McDonald ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Performance Status ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Ecog Performance Status

e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p < 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91]. Further stratification into PD-L1 TPS ≥50% and < 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS < 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS < 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

Effects of Azacitidine (AZA) Vs Conventional Care Regimens (CCR) in Elderly (≥75 years) Patients (Pts) with Myelodysplastic Syndromes (MDS) from the AZA-001 Survival Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3629-3629 ◽  
Author(s):  
John F Seymour ◽  
Pierre Fenaux ◽  
Lewis B. Silverman ◽  
Ghulam J Mufti ◽  
Eva Hellström-Lindberg ◽  
...  
Keyword(s):  
Active Treatment ◽  
Subgroup Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Treatment Options ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Risk Of Death

Abstract Background. A recent phase III trial (AZA-001) showed AZA is the first treatment to significantly extend overall survival (OS) in higher-risk MDS patients (pts) (Blood2007;110:817). MDS incidence increases with age resulting in limited treatment options, particularly for those ≥75 years of age, given the poor tolerability and ineffectiveness of cytotoxic therapies. This subgroup analysis compared the effects of AZA vs CCR on OS, hematologic improvement (HI), transfusion independence (TI), and tolerability in pts ≥75 yrs of age. Methods. Higher-risk MDS (FAB: RAEB, RAEB-T, CMML and IPSS: Int-2 or High) pts were enrolled. All pts were pre-selected by site investigators – based on age, performance status, and comorbidities – to receive 1 of 3 CCR: best supportive care only (BSC); lowdose ara-C (LDAC), or intensive chemotherapy (IC). Pts were then randomized to AZA (75 mg/m2/d SC × 7d q 28d), or to CCR. Those randomized to AZA received AZA; those randomized to CCR received their pre-selected treatment. Randomization was stratified based on FAB subtype (RAEB and RAEB-T) and IPSS (Int-2 or High). Erythropoiesis stimulating agents were disallowed. OS was assessed using Kaplan-Meier (KM) methods and HI and TI were assessed per IWG 2000. To adjust for baseline imbalances, a Cox proportional hazards model was used, with ECOG status, LDH, number of RBC transfusions, Hgb, and presence or absence of -7/del(7q) at baseline as variables in the final model. Adverse events (AEs) were evaluated using NCI-CTC v. 2.0. Results. Of all enrolled pts (N=358, median age 69 yrs), 87 pts (24%) were ≥75 yrs of age (AZA n=38, CCR n=49 [BSC, n=33; LDAC, n=14; IC, n=2]). The majority of pts randomized to CCR received BSC only, suggesting clinicians are generally reticent to use active treatment in this population. Similar to the overall AZA-001 results, treatment with AZA was associated with prolonged survival in pts ≥75 yrs of age, with KM median OS in the AZA group not reached at 17.7 months of follow-up, vs KM median OS for CCR at 10.8 months (HR: 0.48 [95%CI: 0.26, 0.89]; p=0.0193). In these pts, OS rates at 2 years were significantly higher in the AZA group vs CCR: 55% vs 15% (p=0.0003). Two-fold more RBC transfusion-dependent pts at baseline in the AZA group achieved TI vs CCR: 10/23 (44%) vs 7/32 (22%), p=0.1386, respectively. Similarly, more pts in the AZA group achieved HI (major + minor) vs CCR: 58% vs 39%, (p=0.0875), respectively. As previously reported, AZA was generally well tolerated. Anemia, neutropenia, and thrombocytopenia were seen in 42%, 66%, and 71% of pts in the AZA group, respectively, vs 47%, 26%, and 40% in the CCR group, who were predominately receiving BSC only. Infections were reported by 79% and 60% of AZA and CCR pts, respectively. Discontinuations due to an AE occurred in 13% of AZA and 8% of CCR pts ≥75 yrs of age. Conclusion. Data from this subgroup analysis indicate pts ≥75 yrs of age with higher-risk MDS receiving active treatment with AZA experience significantly prolonged 2-year OS and reduced risk of death. AZA is generally well tolerated in this elderly patient population.

Azacitidine Prolongs Overall Survival (OS) and Reduces Infections and Hospitalizations in Patients (Pts) with WHO-Defined Acute Myeloid Leukemia (AML) Compared with Conventional Care Regimens (CCR)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3636-3636 ◽  
Author(s):  
Pierre Fenaux ◽  
Ghulam J Mufti ◽  
Eva Hellström-Lindberg ◽  
Valeria Santini ◽  
Norbert Gattermann ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Poor Response ◽  
Best Supportive Care ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
The Poor ◽  
Response To Chemotherapy

Abstract Background. Azacitidine (AZA), as demonstrated in the phase III trial (AZA-001), is the first MDS treatment to significantly prolong OS in higher-risk MDS pts (Blood2007; 110:817). Approximately one third of the pts enrolled in AZA-001 were FAB RAEB-T (≥20%–30% blasts) and now meet the WHO criteria for AML (Blood1999;17:3835). Considering the poor prognosis (median survival <1 year) and the poor response to chemotherapy in these pts, this subgroup analysis evaluated the effects of AZA vs CCR on OS and on response rates in pts with WHO AML. Methods. The AZA-001 trial enrolled higher-risk MDS pts (FAB: RAEB, RAEB-T, CMML and IPSS: Int-2 or High). Prior to randomization, site investigators preselected (based on age, performance status, and comorbidities) 1 of 3 CCR: best supportive care only (BSC); low-dose ara-C (LDAC), or intensive chemotherapy (IC). Pts were subsequently randomized 1:1 to AZA (75 mg/m2/d SC × 7d q 28d) or CCR; pts randomized to CCR received their investigator preselected treatment. Karyotypes were reclassified using AML standards: favorable {inv 16, t(8;21)}, unfavorable (−7/7q- or complex) and intermediate (all others including normal). OS was assessed by Kaplan-Meier (KM) methods and Cox proportional hazards model; and IWG AML criteria (J Clin Oncol2003;214642–9) were used to assess morphologic complete remissions (CR). Efficacy analyses included all WHO AML pts randomized. All pts were followed until death or study closure. Results. Of 358 enrolled pts, 113 met the definition for WHO AML (median: 23% blasts) of whom 86% were considered unfit for IC and were preselected by investigators to receive a low intensity regimen (BSC or LDAC). 55 of the 113 pts were randomized to AZA and 58 pts to CCR. AZA and CCR groups had comparable baseline demographic and clinical characteristics. Of the 58 pts randomized to CCR, 5 withdrew without receiving treatment and 53 were treated with their investigator preselected treatment as follows: IC (19%;10/53), LDAC (34%; 18/53) and BSC (47 %; 25/53). Of the 55 pts randomized to AZA, 2 withdrew without receiving treatment. Median age was 70 years; 24% had an unfavorable karyotype, 72% had an intermediate karyotype (including 46% normal); no pts had a favorable karyotype. Median follow-up for OS was 20.1 months. Median (min–max) number of treatment cycles was 8 (1–39) for AZA, 2.5 (1–3) for IC; 5.5 (1–14) for LDAC; and 6 months (2 – 19) for BSC. KM median OS was 24.5 vs. 16.0 months, respectively, in the AZA and CCR groups, hazard ratio (HR)=0.47, 95% CI, 0.28 to 0.79, p=0.004, Figure. OS rates at 2 yrs were 50% and 16%, respectively, in the AZA and CCR groups, p=0.0007. There was no statistical difference in the morphologic CR rate between the AZA (18%, 10/55) and CCR groups (16%, 9/58; p=0.80). OS results in cytogenetic intermediate pts showed a significant HR favoring the AZA group (N=38) over CCR (N=43, HR= 0.47 [95% CI: 0.24, 0.91], p=0.024) but not in pts with unfavorable cytogenetics: AZA (N=14) vs CCR (N=13, HR=0.66 [95% CI: 0.26, 1.68], p=0.381); however, pt numbers were low. WHO AML pt outcome measures showed significant benefits with AZA: fewer infections requiring IV antibiotics per pt-year in the AZA group (0.58) vs CCR (1.14, HR=0.51 [95% CI 0.29, 0.78], p=0.003); and reduced rates of hospitalization in the AZA group (3.4 per pt-year) vs CCR (4.3 per pt-year, HR=0.79 [95% CI 0.62, 1.00], p=0.028). AZA was generally well tolerated. Conclusion. AZA significantly prolongs OS with significant improvements in important pt outcomes in elderly WHO AML pts with low marrow blast counts, who currently have limited therapeutic options. Trials are ongoing to confirm the effect of AZA in elderly AML pts with more proliferative disease. Figure. Figure.

Analysis of the GERCOR index in KRAS Exon2 WT patients with mCRC treated with salvage-line cetuximab-based chemotherapy: HGCSG0901.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 781-781
Author(s):  
Ayumu Hosokawa ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Kazuteru Hatanaka ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Impact ◽  
Significant Difference

781 Background: The GERCOR index (GI) based on performance status and serum LDH was reported to be useful to predict survival for patients with previously untreated mCRC. However, in the salvage setting, the validity of the GI has not been reported in patients treated with cetuximab (Cmab)-based chemotherapy. Methods: 269 patients with mCRC treated with Cmab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS Exon2 wild type patients who were refractory to or intolerant of 5-FU / irinotecan/ oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival (OS) were performed using patient characteristics. Survival analyses were performed with the Kaplan-Meier method, log-rank test and the Cox proportional hazards model. The analysis was also designed to determine whether the GERCOR index could be extended to progression-free survival (PFS). Results: All data were available for prognostic categorization in 132 patients. Median OS and PFS were 9.8 and 4.3 months. The distribution and median OS / PFS for GI were as follows: low risk (L)(n = 28; 17.9/3.8 months), intermediate risk (I)(n = 52; 12.2/5.0 months), and high risk (H)(n = 52; 7.5/4.1 months). For OS, there was significant difference between L and H (p < 0.001) and between I and H (p < 0.001), but not between L and I (p = 0.076). For PFS, there was significant difference between I and H (p = 0.017), but not between L and I (p = 0.407), and between L and H (p = 0.222). In the Cox multivariate analysis, GI showed an independent prognostic impact (L vs. I ; HR 2.195, p=0.003 / L vs. H ; HR 4.028, p<0.001), but not predictive impact (L vs. I ; HR 0.987, p=0.958 / L vs. H ; HR 1.314, p=0.268). Conclusions: In this analysis, GI might be a prognostic factor in salvage treatment with Cmab-based chemotherapy.

Time from prior chemotherapy (TFPC) as a prognostic factor in advanced urothelial carcinoma (UC) receiving second-line systemic therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4522-4522
Author(s):  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
David J. Vaughn ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Disease ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Prior Chemotherapy ◽  
Line Therapy

4522 Background: Prognostic factors for overall survival (OS) in patients receiving second-line chemotherapy for advanced platinum-pretreated UC include ECOG performance status (PS) >0, hemoglobin (Hb) <10g/dL and the presence of liver metastasis (LM) (Bellmunt J, J Clin Oncol 2010). We hypothesized that time from prior chemotherapy (TFPC) independently impacts OS. Methods: Of 11 available phase II trials evaluating second-line therapy for advanced UC (n=698), 6 trials with available baseline Hb, PS and LM were utilized (n=534). The trials evaluated vinflunine (2 trials), docetaxel plus vandetanib or placebo, paclitaxel-gemcitabine, nanoparticle-albumin-bound paclitaxel and paclitaxel-cetuximab. The Kaplan-Meier method was used to estimate OS from date of starting second-line therapy. Cox proportional hazards regression stratified for trial was used to evaluate the prognostic effect of factors on OS. TFPC was evaluated as a continuous variable, and based on cutpoints of 3, 6, 9 and 12 months (mo) from prior chemotherapy to first study treatment. The choice of optimal cutpoint for TFPC was determined by the maximum likelihood ratio χ2 statistic. Results: Overall, 513 patients were evaluable. 64.1% received prior chemotherapy for metastatic disease. Median OS was 6.8 mo (95% CI: 6.1 to 7.4); range was 0 to 84.2 mo. Median OS was 5.2, 7.1, 8.8, 7.6 and 10.6 mo respectively for TFPC <3 (n=181), 3 to <6 (n=133), 6 to <9 (n=77), 9 to <12 (n=45) and >12 (n=77) mo, respectively. Shorter TFPC was independently prognostic for decreased survival. The optimal cutpoint for TFPC was <3 mo, but no well-defined plateau was observed. PS>0 (HR=1.72, p<0.001), LM (HR=1.41, p=0.002), Hb <10 g/dl (HR=1.59, p=0.001) and TFPC <3 mo (HR=1.67, p<0.001) were significantly prognostic in the multivariate model. Timing of prior chemotherapy (metastatic disease vs. perioperative) was not prognostic. Conclusions: A shorter duration of TFPC exhibited a significant negative prognostic impact on OS independent of known prognostic factors in patients receiving second-line therapy for advanced UC. If externally validated, TFPC should be a stratification factor in trials of second-line therapy for advanced UC.

Project data sphere (PDS) in prostate cancer: A first look including concomitant medication use.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 204-204
Author(s):  
Bethany Gill ◽  
Leila Khoja ◽  
Zhu Juan Li ◽  
Robert James Hamilton ◽  
Marianne Koritzinsky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Concomitant Medication ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Prognostic Models ◽  
P Value ◽  
Metastatic Site ◽  
Concomitant Medications

204 Background: PDS enables patient-level analyses of control arms of cancer trials. The interface (www.projectdatasphere.org) allows for both web-based and download-based analyses. We aimed to validate established prostate cancer prognostic models and explore the effect of concomitant medications on survival in mCRPC. Methods: Data was obtained for 2,747 control subjects with mCRPC from 7 Phase III clinical trials with 1962 subjects available for OS analyses from 5 studies. Overall survival was estimated using the Kaplan-Meier Method. Cox-proportional hazards models, stratified by trial, were used to estimate hazard ratios. Results: Metastatic site was significant for overall survival (Median: Node only 23.69m, Bone 18.17m, Lung 14.72m, Liver 9.43m; p < 0.001). Of the 23 types of medication examined, after adjusting for metastatic site, patients taking proton pump inhibitors (HR: 1.155, p=0.017) and Erythropoietin (HR: 1.49, p-value<.001) had worse overall survival whilst patients taking fish oil (HR:0.68, p-value=0.033) and non-lipophilic statins (HR:0.69, p=.00277) had improved overall survival. Within the limits of available data, we validated the prognostic models for overall survival proposed by Templeton et al. and Sonpavde et al individually and after inclusion of concomitant medication where patients taking metformin (HR=0.729, p=.0082) and Cox 2 inhibitors (HR=0.708, p=.015) had improved OS whilst those taking low molecular weight heparin (HR=1.352, p=.004) had worse OS. Conclusions: As a first project utilizing open-source PDS data in prostate cancer, we validated two prostate cancer prognostic models and illuminated the ability to undertake novel analyses such as the association of concomitant medications with outcome. Limitations of the data relate to incomplete and inconsistent data entry. Future expansion of patient trials and numbers will help to facilitate future analyses.

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