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.

Association of Surgical Resection, Disability, and Survival in Patients with Glioblastoma

2019 ◽  
Vol 80 (04) ◽  
pp. 262-268 ◽  
Author(s):  
Yahya Ahmadipour ◽  
Monika Kaur ◽  
Daniela Pierscianek ◽  
Oliver Gembruch ◽  
Marvin Darkwah Oppong ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Extent Of Resection ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Surgical Modality ◽  
Supratotal Resection

Objective Extent of resection (EOR) and Karnofsky Performance Status (KPS) are at odds in glioblastoma (GBM) surgery, that is, the anticipated postoperative disability limits the EOR. This study analyzes the correlation of different surgical modalities with the resulting physical status and survival of patients with GBM. Methods A total of 565 patients with primary GBM were operated on in a single institution between 2006 and 2014. Possible surgical modalities comprised supratotal resection (SLR), gross total resection (GTR; ≥ 95% by volume), tumor debulking (TDB; ≤ 95% by volume), and stereotactic biopsy (SB). Pre- and postoperative KPS before and up to 4 weeks after surgery as well as overall survival (OS) rate were determined retrospectively. Hazard ratio (HR) and 95% confidence intervals were calculated using a Cox proportional hazards model. Results Median postoperative KPS was ≥ 70, irrespective of surgical modality. Mean OS was 12.5 months. Multivariate analysis revealed age ≥ 70 years (HR: 1.93), preoperative KPS < 70 (HR: 2.15), and unmethylation in MGMT promoter (HR: 1.27) as independent factors for worse OS. Regarding surgical modality, SB was associated with the worst survival (HR: 2.3) followed by TDB (HR: 1.36). SLR was inferior to GTR (HR: 1.27). Conclusion Higher EOR in patients with GBM does not seem inevitably correlated with increasing functional impairment, but better survival, provided there is a balanced preoperative indication. Nevertheless, SLR does not seem to be superior to GTR. Whenever possible, maximal safe resection should be considered in patients with GBM, even if an EOR ≥ 95% is not possible.

Impact of hemoglobin level on the outcome of advanced non-small-cell lung cancer (NSCLC) treated with cisplatin and gemcitabine

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17010-17010
Author(s):  
O. Juan Vidal ◽  
V. Alberola ◽  
J. Muñoz ◽  
R. De Las Peñas ◽  
C. Camps ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Negative Impact ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Iiib ◽  
Phase Iii ◽  
Number Of Cycles

17010 Background: Negative impact of anemia on survival has been described in NSCLC patients (pts) treated with radiotherapy (RT) or concurrent radiochemotherapy, but scarcely data exist in NSCLC treated with chemotherapy (CT). PURPOUSE: To evaluate the prognosis value of baseline hemoglobin (Hb) among pts with advanced NSCLC treated with cisplatin and gemcitabine. Methods: 433 pts included in two trials conducted by the Spanish Lung Cancer Group (176 pts from the arm A of a randomized phase III trial comparing 3 regimens of CT and 257 pts from a phase II trial) were included in this analysis. No significant differences in baseline characteristics, response and survival (median 8.73 and 9.87 months, p=0.46) were observed between pts of the two trials. The baseline Hb and other potential risk factors for survival were analyzed with Cox Proportional Hazards model in an univariate an multivariate analysis. Results: Stage IIIB with positive pleural effusion (25%), stage IV (75%). 85% had ECOG PS 0–1. Median age: 60 years (range 31–82). 89% male. Histology: 41% adenocarcinoma, 39% squamous cell, 6.5% large cell, 14.5% NSCLC not otherwise specified. Median number of cycles received was 4 (range 1–8). Mean Hb level prior CT was 13.2 g/dl (range 8 to 19.6 g/dl). Response rate was 41% and median survival was 9.57 months (95% CI: 8.57–11–57). No statistically differences in survival were observed by stage (IIIB vs IV), age and gender. In the univariate analysis, number of cycles received (≤3 vs. >3 cycles), ECOG (2 vs 0–1), response (SD+PD vs CR+PR), baseline Hb (≤11 vs >11 gr/dl); minimum Hb during the CT (<10 vs ≥10) and second line CT (No vs Yes) emerged as prognostic factors for survival and were introduced in the multivariate model (see Table ). Conclusions: Hb level at the initiation of CT is an independent prognostic factor of survival this homogenous group of advanced NSCLC treated with cisplatin and gemcitabine. Baseline Hb should be considered as prognosis factor for survival in addition to ECOG. [Table: see text] No significant financial relationships to disclose.

Final overall survival and updated biomarker analysis results from the randomized phase III ICOGEN trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7559-7559 ◽  
Author(s):  
Yan Sun ◽  
Yuankai Shi ◽  
Li Zhang ◽  
Xiaoqing Liu ◽  
Caicun Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Significant Difference ◽  
Biomarker Analysis ◽  
Nsclc Patients

7559 Background: A total of 399 pretreated patients with advanced NSCLC were randomly assigned to receive gefitinib or icotinib in the phase III ICOGEN trial, the first head-to-head phase III trial of EGFR-TKIs. The results of the primary endpoint, PFS, have been reported previously. This report represents the final OS and biomarker analysis results. Methods: EGFR mutation was evaluated by using Scorpion ARMS (QIAGEN, n=152). Overall survival was analyzed by Cox proportional-hazards model analysis at 82% maturity. Results: Median OS was 13.3 months for icotinib and 13.9 months for gefitinib (hazard ratio [HR] = 0.90; 95% CI, 0.79 to 1.02; P = .109). The EGFR mutation rate was 43% in the icotinib group and 59% in the gefitinib group. Compared to wild type patients, patients with EGFR mutation had longer PFS (median, 6.2m vs. 2.3m; P=.00001) as well as OS (median, 20.5m vs. 7.7m; P=.00001). There were no significant differences in PFS or OS between the two treatment groups in EGFR mutation-positive subgroup (median PFS, 7.8m vs. 5.3m for icotinib and gefitinib, respectively, P =.3162; median OS, 20.9m vs. 20.2m for icotinib and gefitinib, respectively, P =.7611.) or in EGFR mutation-negative subgroup (median PFS, 2.3m vs. 2.2m for icotinib and gefitinib, respectively, P =.1531; median OS, 7.8m vs. 6.9m for icotinib and gefitinib, respectively, P =.7885.). Conclusions: There is no statistically significant difference between icotinib and gefitinib in PFS or OS when given to NSCLC patients. This suggests that icotinib can provide similar OS benefits to gefitinib in advanced NSCLC patients. Moreover, EGFR mutation status is the strongest predictor in identifying which patients are most likely to benefit from icotinib.

scholarly journals Survival of Patients with Hepatocellular Carcinoma in Renal Insufficiency: Prognostic Role of Albumin-Bilirubin Grade

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1130
Author(s):  
Shu-Yein Ho ◽  
Chia-Yang Hsu ◽  
Po-Hong Liu ◽  
Chih-Chieh Ko ◽  
Yi-Hsiang Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Renal Insufficiency ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Prognostic Role ◽  
The Impact

Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade in this special setting is unclear. We aimed to investigate the role of ALBI grade associated with the impact of RI on HCC. A prospective cohort of 3690 HCC patients between 2002 and 2016 were retrospectively analyzed. The Kaplan–Meier method and multivariate Cox proportional hazards model were used to determine survival and independent prognostic predictors. Of all patients, RI was an independent predictor associated with decreased survival. In multivariate Cox analysis for patients with RI, α-fetoprotein level ≥20 ng/mL, tumor size >3 cm, vascular invasion, distant metastasis, presence of ascites, performance status 1–2, performance status 3–4, and ALBI grade 2 and grade 3 were independent predictors of decreased survival (all p < 0.05). In subgroup analysis of patients with RI undergoing curative and non-curative treatments, the ALBI grade remained a significant prognostic predictor associated with decreased survival (p < 0.001). In summary, HCC patients with RI have decreased survival compared to those without RI. The ALBI grade can discriminate the survival in patients with RI independent of treatment strategy and is a feasible prognostic tool in this special patient population.

Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: Survival and biomarker analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5023-5023 ◽  
Author(s):  
R. M. Bukowski ◽  
T. Eisen ◽  
C. Szczylik ◽  
W. M. Stadler ◽  
R. Simantov ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Vegf Signaling ◽  
Hazards Model ◽  
Biomarker Analysis ◽  
Tumor Biopsies

5023 Background: Based on the significant PFS benefit of sorafenib (SOR) vs placebo (P) in a Phase III advanced RCC trial, P patients were unblinded and crossed over to SOR in May 2005. Final OS and biomarker data are reported. Methods: Final OS analysis was planned at ∼540 events (a=0.037 after adjusting for previous analyses). To minimize effect of crossover on OS, a secondary analysis was planned censoring P data on June 30, 2005 (a=0.037). Plasma VEGF and sVEGFR2 were measured by ELISA at baseline (BL), cycle (C) 1 day (D) 21, and C3D1. pERK was assayed by IHC. Results: 903 patients were randomized (SOR, 451; P, 452). The only OS analysis before crossover (May 2005) showed an estimated 39% OS improvement for SOR vs P (HR=0.72; p=0.018) (ECCO 2005); 216 P patients had crossed to SOR. OS analysis 6 months after crossover (Nov 2005) showed a 30% improvement in OS for SOR vs P (HR=0.77, p=0.015) (ASCO 2006). These OS differences did not reach prespecified O’Brien-Fleming statistical boundaries. Final OS (Sep 2006) at 561 deaths showed an improvement of 13.5% for SOR vs P and was not significant (median 17.8 vs 15.2 months; HR=0.88; p=0.146; a=0.037). Secondary analysis censoring P data (June 2005) showed a significant OS benefit for SOR vs P (HR=0.78, 95% CI: 0.62, 0.97; p=0.0287; a=0.037), suggesting crossover had confounded OS. Changes in VEGF (n=712) and sVEGFR2 (n=717) were observed after SOR treatment (AACR 2006); VEGF increased 32% (n=279) at C1D21 and 47% (n=203) at C3D1, and sVEGFR2 decreased 18% (n=282) and 24% (n=206). Using a COX proportional hazards model, BL VEGF was an independent prognostic factor (p=0.014); patients with high BL VEGF (>131 pg/ml) had poorer prognosis and a trend towards greater PFS benefit with SOR (SOR vs P, HR=0.48 vs 0.64 for high vs low VEGF, p=0.096). BL sVEGFR2, changes in VEGF or sVEGFR2 at C1D21, and pERK levels in limited diagnostic tumor biopsies were not predictive of SOR response. Conclusion: SOR demonstrated a PFS benefit in advanced RCC, although ITT final OS analysis showed a confounding effect of crossover. Significant OS benefit of SOR was seen in a planned secondary analysis adjusting for crossover. VEGF levels have prognostic importance, and SOR-associated changes in VEGF and sVEGFR2 are consistent with inhibition of VEGF signaling. No significant financial relationships to disclose.

Liver metastases (LM) to predict for short overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4655-4655 ◽  
Author(s):  
William Kevin Kelly ◽  
Susan Halabi ◽  
Michael Anthony Carducci ◽  
Daniel J. George ◽  
John Francis Mahoney ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Data Set

4655 Background: Patients withCRPC with LM represent a subset of patients with a poor prognosis. An exploratory analysis was performed to evaluate the difference in baseline characteristics and clinical outcomes in patients with and without LM from a randomized phase III trial (CALGB 90401) in men with mCRPC. Methods: Data from 1,050 men treated with docetaxel, prednisone with either bevacizumab or placebo were used. Pts were chemotherapy naïve, and had evidence of progressive mCRPC despite castrate testosterone levels and anti-androgen withdrawal, ECOG performance status ≤ 2, and adequate bone marrow, hepatic and renal functions. The proportional hazards model was used to assess the prognostic significance of LM in predicting OS and progression free survival (PFS) adjusting for stratification factors. Results: Fifty-nine (5.6%) of the 1045 pts with a complete data set had documented LM. Patients with LM had higher baseline alkaline phosphatase (ALK, 167 vs 117 U/L, p =0.0205) and lactate dehydrogenase (LDH, 262 vs 205 U/L, p =0.0001) compared to patients without LM. There were strong associations between LM status and lung metastasis (p=0.0004) and other visceral disease (p=<0.001) but not with bone disease. Clinical outcomes as a function of LM status are listed in the table. The median OS time in LM pts was 14.4 compared to 22.6 months, with a hazard ratio (HR) 1.4. The HR for treatment effect (DP+B vs. DP) for LM was not statistically significant for either group. Conclusions: Compared to pts without LM, mCRPC with LM are characterized by higher LDH and ALK and have a poor OS despite having similar PFS and objectivebiochemical response to docetaxel based therapy. [Table: see text]

CA19-9 decrease at 8 weeks as a predictor of overall survival (OS) in a randomized phase III trial (MPACT) of weekly nab-paclitaxel (nab-P) plus gemcitabine (G) versus G alone in patients with metastatic pancreatic cancer (MPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4058-4058 ◽  
Author(s):  
E. Gabriela Chiorean ◽  
Daniel D. Von Hoff ◽  
Thomas J. Ervin ◽  
Francis P. Arena ◽  
Jeffrey R. Infante ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Rank Test ◽  
Hazards Model ◽  
Relationship Of ◽  
To Receive ◽  
The Relationship

4058^ Background: nab-P + G showed promising efficacy in a phase I/II study in MPC, and decreases in CA19-9 correlated with OS. In MPACT, patients (pts) who received nab-P + G vs G had improved median OS (8.5 vs 6.7 mo; HR 0.72; p = 0.000015), PFS (5.5 vs 3.7 mo; HR 0.69; p = 0.000024) and ORR (23% vs 7%; p = 1.1 × 10−10). Here we present a prespecified exploratory analysis of CA19-9 from the MPACT trial. Methods: 861 previously untreated pts with MPC were randomized 1:1 to receive nab-P 125 mg/m2 + G 1000 mg/m2 days 1, 8, and 15 every 4 weeks or G alone 1000 mg/m2 weekly for 7 weeks followed by a week of rest (cycle 1) and then days 1, 8, and 15 every 4 weeks (cycle ≥ 2). CA19-9 was evaluated at baseline and then every 8 weeks. OS comparisons at different CA19-9 criteria were performed by stratified Cox proportional hazards model (P by stratified log-rank test using randomization criteria). Results: 750 pts had an evaluable CA19-9 at baseline. More pts in the nab-P + G arm vs the G arm demonstrated a best CA19-9 decrease from baseline of ≥ 20% and ≥ 90% (61% vs 44% and 31% vs 14%, respectively; Table). At the first postbaseline assessment (week 8), greater proportions of pts in the nab-P + G arm vs the G arm had CA19-9 decreases of ≥ 20% and ≥ 90% (Table). At that time point, for pts with a decrease of ≥ 20% in CA19-9, nab-P + G demonstrated a significantly longer OS vs G. The risk reduction for pts with a ≥ 90% decrease was greater than in pts with a ≥ 20% decrease. In pts with an 8-week CA19-9 decrease < 20%, median OS for nab-P + G vs G was 8.3 vs 8.0 mo (HR 0.92; p = 0.705). The relationship of CA19-9 kinetics with OS will also be examined. Conclusions: Higher proportions of pts in the nab-P + G arm had CA 19-9 responses of ≥ 20% and ≥ 90% vs the G arm. Pts who achieved a CA19-9 decrease at 8 weeks of ≥ 20% or ≥ 90% had significantly longer OS with nab-P + G than with G. Clinical trial information: NCT00844649. [Table: see text]

Relationship between biomarkers and everolimus efficacy in the phase III RECORD-1 trial of patients with metastatic renal cell carcinoma (mRCC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 352-352
Author(s):  
Stephane Oudard ◽  
Bernard J. Escudier ◽  
John A. Thompson ◽  
Viktor Grünwald ◽  
Cristina Masini ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Time Course ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Day Treatment ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Continuous Variables ◽  
Baseline Levels

352 Background: Compared with placebo, everolimus provided significant improvement in median PFS in the RECORD-1 study of VEGFr-TKI-refractory mRCC. To investigate the role of angiogenesis pathway molecules as potential biomarkers of everolimus efficacy in RECORD-1, plasma levels of sVEGFR-2, VEGF-A, and bFGF were estimated. Methods: In addition to best supportive care, patients received everolimus 10 mg/day (n = 277) or placebo (n = 139). Placebo patients who progressed were offered everolimus. Predose blood samples were collected on day 1 of the first four 28-day treatment cycles. Plasma levels of sVEGFR-2, VEGF-A, and bFGF were assessed by ELISA. Effect of treatment over time on each biomarker was assessed by a mixed effects model. Hazard ratios (HR) for prognostic effects were obtained using log baseline biomarker values as continuous variables in a stratified Cox proportional hazards model. Results: Plasma levels of sVEGFR-2, VEGF-A, and bFGF were available for 45%, 45%, and 39% of everolimus patients and 50%, 50%, and 45% of placebo patients. Patients with biomarker data had baseline characteristics similar to those of the overall population. Mean baseline levels (pg/mL) of sVEGFR-2, VEGF-A, and bFGF were similar for everolimus (8945, 245, and 8, respectively) and placebo (8985, 253, and 13, respectively). Everolimus significantly improved median PFS over placebo irrespective of baseline levels of the analyzed biomarkers (p < 0.001), indicating they are not predictive of everolimus efficacy. Prolonged PFS in the biomarker population was associated with lower VEGF-A baseline level (HR, 1.27; 95% CI, 1.03-1.57; p = 0.028), suggesting VEGF-A may be prognostic for mRCC. Compared with placebo, everolimus significantly reduced bFGF (p = 0.0095) and sVEGFR-2 (p< 0.001) levels over the time course of the study; no effect on VEGF-A levels was observed. Conclusions: Everolimus significantly improved PFS compared with placebo, regardless of baseline biomarker levels. Lower VEGF-A levels may be a potential prognostic factor for longer PFS. Everolimus treatment significantly downregulated plasma levels of bFGF and sVEGFR-2 from baseline. Clinical trial information: NCT00410124.

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