Correlation of survival with tumor histology, age, and prognostic risk group for previously untreated patients with advanced renal cell carcinoma (adv RCC) receiving temsirolimus (TEMSR) or interferon-alpha (IFN)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5033-5033 ◽  
Author(s):  
J. P. Dutcher ◽  
C. Szczylik ◽  
N. Tannir ◽  
P. Benedetto ◽  
P. Ruff ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Tumor Histology ◽  
Poor Risk ◽  
Hazards Model

5033 Background: Temsirolimus is a novel mTOR inhibitor and has demonstrated significantly longer overall survival (OS, P=0.0069) and progression-free survival (PFS, P=0.0001) vs IFN for patients (pts) with previously untreated adv RCC with poor-risk features (Hudes et al. ASCO 2006). Planned and post-hoc analyses were performed to assess the influence of tumor histology (clear- cell vs other), age (<65 y vs =65 y), and prognostic-risk groups (intermediate vs poor; Motzer et al. JCO 20:289) on survival in pts treated with TEMSR or IFN. Methods: Pts received IFN 3 million units [MU] subcutaneously 3x weekly, escalating to 18 MU; TEMSR 25-mg intravenous infusion weekly; or TEMSR 15-mg infusion plus IFN 6 MU. Kaplan-Meier analysis and a Cox proportional hazards model were used to analyze OS and PFS for pt subsets. Histologies were reported by investigators. Results: The proportion of pts with different histologies was balanced across the 2 arms (81% clear-cell; 13% indeterminate, 6% non-clear-cell). Of those with additional subtype data, 75% were papillary. For pts with clear-cell tumors, median OS and PFS were longer for TEMSR vs IFN with hazard ratios (HR) of 0.82 and 0.76, respectively ( Table ). For pts with other tumor histologies, median OS and PFS also were longer for TEMSR vs IFN with HR of 0.49 and 0.38, respectively. Among pts <65 y, median OS and PFS were longer for TEMSR than for IFN (OS: TEMSR [n=145] 12.0 mo; IFN [n=142] 6.9 mo; HR=0.62 [95% CI, 0.47, 0.82]; PFS: TEMSR 5.6 mo; IFN 3.1 mo; HR=0.61 [0.47, 0.79]). There was no difference in OS or PFS for pts =65 y treated with TEMSR or IFN but TEMSR had a better side effect profile than IFN. OS and PFS for pts with intermediate- or poor-risk features will be reported. Conclusions: TEMSR benefits pts with clear-cell RCC and other histologies as well as younger and older pts. [Table: see text] No significant financial relationships to disclose.

Circulating mir-21 and mir-378 are predictive of progression-free survival (PFS) in patients treated with everolimus in metastatic renal cell cancer (mRCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4617-4617
Author(s):  
James Lin Chen ◽  
Kimryn Rathmell ◽  
David F. McDermott ◽  
Walter Michael Stadler
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Clear Cell ◽  
Standard Dose ◽  
Cell Cancer ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Negative Control ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

4617 Background: The oral mTOR inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and modestly delays RCC progression. We hypothesized that circulating microRNAs, which have been associated with renal cancer and inflammation, may serve as predictive biomarkers to help better define a population more sensitive to treatment. Methods: Plasma from mRCC pts refractory to VEGF inhibition were obtained prior to treatment with standard dose everolimus as part of a clinical trial examining FDG-PET as a potential predictive biomarker. As we were specifically interested in tumor response to drug, only pts who died, remained on trial, or had radiographic progression by RECIST criteria were profiled. Pts who were unable to tolerate drug were excluded. MicroRNAs were extracted and profiled without pre-amplification using Exiqon LNA PCR panels. Crossing point (Cp) values within 5 of the negative control were removed. MicroRNAs must have been present in >90% of samples and varied at least p > 0.10 from mean to be further analyzed. Cox-proportional hazards model and Kaplan-Meier analyses were performed. Results: 28 patients had available plasma and met criteria for profiling. Pt characteristics included: 20 (71%) clear cell histology, median age 57.7 (43 – 76), median number of prior systemic therapies 2 (1 – 3). 103 microRNAs were expressed in at least 90% of all samples. Mir-21 and mir-378 were independently correlated with PFS (FDR: 0.02 and 0.06, respectively). Low circulating plasma mir-21 and mir-378 levels resulted in a median PFS prolongation of 370d vs. 101d (p=0.027) and 368d vs. 106d (p=0.001). Analysis of the clear cell cohort for mir-21 and mir-378 also demonstrated a significant median PFS difference of 350d vs. 173d (p=0.045) and 345d vs. 147d (p=0.004). Conclusions: Elevated levels of circulating mir-21 and mir-378 have been associated with systemic inflammatory states, and in our study are correlated with decreased PFS in mRCC pts undergoing everolimus therapy. Further prospective studies will be required to validate these exploratory results for their potential role as prognostic or predictive biomarkers.

A multivariate analysis of prognostic factors from assure (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 618-618
Author(s):  
Naomi B. Haas ◽  
Judith Manola ◽  
Robert G. Uzzo ◽  
Keith Flaherty ◽  
Michael Pins ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Clear Cell ◽  
Locally Advanced ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Risk Category ◽  
Fuhrman Grade ◽  
Hazards Model ◽  
Postoperative Setting

618 Background: Previous post-surgical prognostic nomograms for clear cell RCC are based upon TNM stage, PS, Fuhrman grade, and sometimes presence of necrosis. 1943 patients (pts) with locally advanced renal cell carcinoma (RCC) participated in the ASSURE trial of one year of sunitinib daily for 4 wks of a 6 wk cycle, sorafenib daily, or placebo, then treated for up to 9 cycles. Of these, 1541 pts had clear cell predominant features. There were no significant differences in DFS (median 5.7 years) between either of the experimental arms and placebo, in the total or clear cell population. We investigated site-reported clinical and surgical factors associated with prolonged DFS. Methods: Patients were staged according to the AJCC 2007 version. Factors considered in addition to those in the final model shown below were age, race/ethnicity, histology, risk category and PS as stratified, and 10 other specific baseline symptoms. A Cox proportional hazards model was built including factors that significantly changed the -2 log likelihood ratio (Collett). Results: Shorter DFS was associated with higher age, stage and Fuhrman grade, male sex, PS > 0, open vs. laparoscopic surgical approach, low hemoglobin and diagnosis based on presence of symptoms. Conclusions: The association of stage, grade, age, and PS with outcome confirms previous analyses in resectable disease. The same factors which predict outcome in metastatic disease now clearly confer relapse risk in the postoperative setting. Clinical trial information: NCT00326898. [Table: see text]

Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4500-4500 ◽  
Author(s):  
Brian I. Rini ◽  
Elizabeth R. Plimack ◽  
Viktor Stus ◽  
Rustem Gafanov ◽  
Robert Hawkins ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Risk Group ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line ◽  
Poor Risk ◽  
First Line Therapy ◽  
Line Therapy

4500 Background: In KEYNOTE-426, pembro + axi significantly improved OS (HR 0.53, P < .0001), PFS (HR 0.69, P = .0001), and ORR (59.3% vs 35.7%, P < .0001) vs sunitinib and had manageable toxicity as first-line therapy for mRCC (NCT02853331). The pembro + axi benefit was observed across all IMDC risk groups and regardless of PD-L1 expression. We present data for the combined intermediate/poor risk group and for patients (pts) with sarcomatoid features. Methods: 861 eligible pts with clear-cell mRCC, no prior systemic therapy for mRCC, and KPS ≥70 were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID (N = 432) or sunitinib 50 mg orally QD (4-wk on/2-wk off) (N = 429). Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR (RECIST v1.1 by BICR) was the key secondary endpoint. The intermediate/poor risk group was prespecified; the sarcomatoid group was exploratory. HRs and their 95% CIs were calculated with a Cox proportional hazards model. None of the analyses were multiplicity-controlled. Results: 592 (68.8%) of all randomized pts were of IMDC intermediate/poor risk — 294 in the pembro + axi arm, 298 in the sunitinib arm. Pembro + axi improved OS (HR 0.52, 95% CI 0.37-0.74; 12-mo rate 87.3% vs 71.3%), PFS (HR 0.67, 95% CI 0.53-0.85; median 12.6 vs 8.2 mo), and ORR (55.8% [95% CI 49.9-61.5] vs 29.5% [24.4-35.1]) in pts with intermediate/poor risk; CR rates were 4.8% (95% CI 2.6-7.9) vs 0.7% (0.1-2.4). Of the 578 pts with known status, 105 (18.2%) had sarcomatoid features — 51 in the pembro + axi arm, 54 in the sunitinib arm. Pembro + axi improved OS (HR 0.58, 95% CI 0.21-1.59; 12-mo rate 83.4% vs 79.5%), PFS (HR 0.54, 95% CI 0.29-1.00; median not reached vs 8.4 mo), and ORR (58.8% [95% CI 44.2-72.4] vs 31.5% [19.5-45.6]) in pts with sarcomatoid features; CR rates were 11.8% (95% CI 4.4-23.9) vs 0% (0.0-6.6). Conclusions: Pembro + axi provides benefit in the combined population of pts with IMDC intermediate or poor risk and in pts whose tumors had sarcomatoid features. The observed benefits were consistent with those seen in the total population. Clinical trial information: NCT02853331.

scholarly journals Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuqi Sun ◽  
Jie Mei ◽  
Wenping Lin ◽  
Ziliang Yang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Binary Logistic Regression ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Related Factors ◽  
Hazards Model ◽  
Before And After

Abstract Background Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy. Methods A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS. Results Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006). Conclusion Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.

Randomized phase II study of panitumumab (Pmab) + irinotecan (CPT-11) versus cetuximab (Cmab) + CPT-11 in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) after fluoropyrimidine (FU), CPT-11, and oxaliplatin (L-OHP) failure: WJOG6510G.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 661-661 ◽  
Author(s):  
Naotoshi Sugimoto ◽  
Daisuke Sakai ◽  
Takao Tamura ◽  
Hiroki Hara ◽  
Tomohiro Nishina ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Efficacy Analysis ◽  
Hazards Model ◽  
Previously Treated ◽  
Grade 3

661 Background: Continuation of CPT-11 in combination with Cmab after CPT-11 failure has a survival benefit over Cmab alone. However, it is not clear whether CPT-11 with Pmab shows similar benefits. Methods: Pts with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies were randomized 1:1 to either Cmab + CPT-11(Cmab arm), or Pmab + CPT-11(Pmab arm). Primary objective was progression free survival (PFS), with an expected hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (80% CI) using cox proportional hazards model. Median PFS with both arms were assumed to be 6.0 months. Secondary objectives were overall survival (OS), response rate (RR), disease control rate (DCR), and safety. Results: From December 2011 to September 2014, 121 pts were enrolled from 31 sites in Japan. Because 1 patient declined before treatment, totally, 120 (Cmab arm: 59, Pmab arm 61) pts were eligible for efficacy analysis. Baseline characteristics were well balanced between the two arms. 116 pts (96.7 %) were previously treated with bevacizumab. Efficacy results are shown in the table. The common grade 3 or 4 adverse events in Cmab/Pmab arm were leukopenia 19.0/3.3%, neutropenia 27.6/8.3%, hypomagnesaemia 6.9/16.7%, and rash 5.2/13.3 %, respectively. Conclusions: Non-inferiority of Pmab to Cmab in combination with CPT-11 was suggested for patients with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies, associated with favorable PFS and OS. Clinical trial information: UMIN000006643. [Table: see text]

Evaluation of brain metastasis in JAVELIN Renal 101: Efficacy of avelumab + axitinib (A+Ax) versus sunitinib (S).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 687-687 ◽  
Author(s):  
Eric Jonasch ◽  
Elshad Hasanov ◽  
Robert J. Motzer ◽  
Subramanian Hariharan ◽  
Toni K. Choueiri ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Disease Site

687 Background: Patients (pts) with brain metastasis from renal cell carcinoma (RCC) have poor prognosis and are often excluded from randomized registrational trials. The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) for A+Ax vs S in pts with advanced RCC (Motzer NEJM 2019). The activity of A+Ax in pts with brain metastasis enrolled in JAVELIN Renal 101 is presented. Methods: PFS was compared between treatment arms for the subgroup of pts randomized in JAVELIN Renal 101 with brain metastases at enrollment (pts with brain disease site prior to randomization by blinded independent central review [BICR] or by investigator assessment). PFS time was summarized per BICR assessment by treatment arm using the Kaplan-Meier method. The Cox proportional hazards model was fitted to compute the hazard ratio (HR) and the corresponding CI. In addition, time to brain metastasis was assessed for pts without brain metastasis by BICR at enrollment after treating death as a competing risk. Results: Of all randomized pts (A+Ax arm, N=442; S, N=444), 23 in each arm (5.2%) had asymptomatic brain metastasis at enrollment; of these, pts assigned to A+Ax had a PFS of 4.9 mo (95% CI: 1.6, 5.7) vs 2.8 mo (95% CI: 2.3, 5.6) for pts assigned to S (HR: 0.90; 95% CI: 0.43, 1.88). Among pts without brain metastasis at enrollment, 8 pts on the A+Ax arm and 10 on the S arm developed brain metastasis during the trial, based on BICR assessment; 17/18 occurred ≤12 mo from randomization. The cumulative incidence rate of brain metastasis at 18 mo was 2% (95% CI: 0.6, 3.3) for the A+Ax arm and 3% (95% CI: 1.1, 4.8) for the S arm. Conclusions: In this post hoc exploratory analysis of JAVELIN Renal 101, the observed PFS among pts with brain metastasis at enrollment was similar between the two arms, with HR and median PFS numerically favoring A+Ax. Pts on the S arm had a numerically higher incidence of new brain metastases on trial. Outcomes are poor in pts with advanced RCC and brain metastasis; more effective treatments are needed. Clinical trial information: NCT02684006.

Updated overall survival (OS) results from the phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2- advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1001-1001
Author(s):  
Dennis J. Slamon ◽  
Patrick Neven ◽  
Stephen K. L. Chia ◽  
Guy Heinrich Maria Jerusalem ◽  
Michelino De Laurentiis ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Term Survival ◽  
Free Survival ◽  
Hazards Model

1001 Background: The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2− ABC (median, not reached vs 40.0 mo; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92, P =.00455). This analysis was final per the protocol; following the unblinding of the study, pts still on study treatment in the PBO arm were allowed to cross over to the RIB arm. We report an exploratory analysis of OS after an additional median 16.9 mo of follow-up, allowing for further characterization of long-term survival benefits of RIB. Methods: Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. Updated OS was evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional postprogression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT), and CT-free survival were also evaluated and summarized. Results: At the data cutoff (Oct 30, 2020), the median follow-up was 56.3 mo (min, 52.7 mo) and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the RIB vs PBO arms, respectively. With this extended follow-up, RIB + FUL continued to demonstrate an OS benefit vs PBO + FUL (median, 53.7 vs 41.5 mo; HR, 0.73; 95% CI, 0.59-0.90). RIB + FUL had prolonged OS vs PBO + FUL in the 1L (median, not reached vs 51.8 mo; HR, 0.64; 95% CI, 0.46-0.88) and 2L subgroups (median, 39.7 vs 33.7 mo; HR, 0.78; 95% CI, 0.59-1.04). Subgroup analyses also showed a consistent OS benefit compared with the intent-to-treat (ITT) population for most subgroups. PFS2, time to CT, and CT-free survival for the ITT population favored RIB + FUL (Table). Among pts who discontinued study treatment, 81.9% and 86.4% received a next-line subsequent antineoplastic therapy, while 14.0% and 30.0% received a CDK4/6i as any subsequent line in the RIB vs PBO arms, respectively. No new safety signals were observed. Conclusions: The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO + FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2− ABC. The OS benefit of RIB was observed in the 1L and 2L subgroups, which further supports the use of RIB in these populations. The results also demonstrated a significant delay in the use of subsequent CT with RIB vs PBO. Clinical trial information: NCT02422615 .[Table: see text]

Once-weekly (70 mg/m2) versus twice-weekly (56 mg/m2) dosing of carfilzomib (CFZ) for patients (pts) with relapsed and/or refractory multiple myeloma (RRMM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19505-e19505
Author(s):  
Philippe Moreau ◽  
A. Keith Stewart ◽  
Meletios A. Dimopoulos ◽  
David Samuel DiCapua Siegel ◽  
Thierry Facon ◽  
...  
Keyword(s):  
Adverse Events ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Prior Therapy ◽  
Hazards Model ◽  
Grade 3 ◽  
Post Hoc

e19505 Background: CFZ combined with dexamethasone is approved to treat pts with RRMM, with CFZ given once-weekly at 70 mg/m2 (Kd70 QW) or twice-weekly at 56 mg/m2 (Kd56 BIW). No randomized trials have directly compared Kd70 QW with Kd56 BIW. We performed a post hoc comparison between pts who received Kd56 BIW in the ENDEAVOR trial and pts who received Kd70 QW in the A.R.R.O.W. or CHAMPION-1 trials. Methods: Data were analyzed from 3 trials of CFZ in RRMM: A.R.R.O.W. (240 pts in Kd70 QW arm; 2–3 prior therapies and refractory to most recent therapy), CHAMPION-1 (104 pts received Kd70 QW; 1–3 prior therapies), and ENDEAVOR (464 pts in Kd56 BIW arm; 1–3 prior therapies). Pts who received Kd70 QW in A.R.R.O.W. and CHAMPION-1 were pooled and compared with pts who received Kd56 BIW in ENDEAVOR. As study populations slightly varied among the 3 trials, an analysis of safety and efficacy was performed in a subgroup of pts who received 2–3 prior therapy lines and were not refractory to bortezomib (BTZ). Also, we performed regression analyses (controlling for age, ISS stage, BTZ and lenalidomide refractory status, and number of prior regimens) among all pts in the trials who received Kd70 QW or Kd56 BIW. Results: Among BTZ non-refractory pts with 2–3 lines of prior therapy, median progression-free survival (PFS) was 12.1 months (95% CI 8.4–14.3) for Kd70 QW (n = 146) and 14.5 months (95% CI 10.2–NE) for Kd56 BIW (n = 217), and the overall response rate (ORR) was 69.9% (95% CI 61.7–77.2) for Kd70 QW and 72.4% (95% CI 65.9–78.2) for Kd56 BIW. The rate of grade ≥3 adverse events (Kd70 QW vs Kd56 BIW) was 67.6% and 85.3%; among adverse events of interest, the grade ≥3 rate was 1.4% and 5.1% for cardiac failure, 3.4% and 6.0% for renal failure, and 5.5% and 15.7% for hypertension. Kd70 QW represents a convenient and well-tolerated treatment modality for pts with RRMM. In a Cox proportional hazards model, the hazard ratio for PFS (Kd70 QW vs Kd56 BIW) was 0.91 (95% CI 0.69–1.19), and in a logistic regression model the odds ratio for ORR (Kd70 QW vs Kd56 BIW) was 1.12 (95% CI 0.74–1.69). Conclusions: This post hoc analysis suggests that once-weekly Kd70 has a comparable benefit-risk profile to twice-weekly Kd56. Clinical trial information: NCT02412878, NCT01677858, NCT01568866.

scholarly journals Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Cerebrovascular Events ◽  
Long Term Follow Up ◽  
Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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