Final analysis of phase III LATITUDE study in patients (pts) with newly diagnosed high-risk metastatic castration-naïve prostate cancer (NDx-HR mCNPC) treated with abiraterone acetate + prednisone (AA+P) added to androgen deprivation therapy (ADT).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 141-141 ◽  
Author(s):  
Karim Fizazi ◽  
Namphuong Tran ◽  
Luis Enrique Fein ◽  
Nobuaki Matsubara ◽  
Alfredo Rodríguez Antolín ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Standard Of Care ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Hazards Model ◽  
Total Death ◽  
Secondary Endpoints

141 Background: The first and second interim analyses (IA1 and IA2) of the LATITUDE study in NDx-HR mCNPC pts with addition of AA+P to ADT vs placebo (PBO)+ADT showed significant benefit in the coprimary endpoints of overall survival (OS) and radiographic progression free survival (rPFS), and secondary endpoints. Final OS analysis and updated safety results are presented. Methods: 1,199 pts were randomized (1:1) to AA (1 g QD) + P (5 mg QD) + ADT or PBO + ADT. Primary endpoint of OS and secondary endpoints were assessed (stratified proportional hazards model), and adverse events (AEs) were summarized from final analysis, which was planned for around 852 total death events. Results: Final analysis was conducted after a median follow-up of 51.8 mo (~22 mo from IA1) and 618 deaths were observed (275 [46%] in AA+P and 343 [57%] in PBO). Treatment was ongoing for 157 (26.3%) pts in AA+P; 72 (12.0%) crossed over from PBO to AA+P, of which 59 (81.9%) remained on treatment. AA+P treatment continued to show significant OS benefits vs PBO (HR: 0.7, 95% CI: 0.6-0.8; p<0.0001), along with significant improvements in secondary endpoints (table). Serious AEs were reported in 32.2% pts in AA+P and 25.1% in PBO. Grade 3/4 AEs of special interest (AA+P vs PBO; %) were hypertension (21.9 vs 10.5), hypokalemia (11.7 vs 1.7), hepatotoxicity (8.9 vs 3.5), cardiac disorders (3.9 vs 1) and fluid retention (0.8 vs 1). Conclusions: The final analysis continues to demonstrate a significant OS advantage of combining AA+P to ADT in NDx-HR mCNPC pts. These efficacy findings and AE profiles are consistent with IA1 and IA2 and reinforce AA+P as a standard of care in NDx-HR mCNPC pts. Clinical trial information: NCT01715285. [Table: see text]

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]

AR-V7 and prediction of benefit with taxane therapy: Final analysis of PROPHECY.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 184-184
Author(s):  
Andrew J. Armstrong ◽  
Jun Luo ◽  
Monika Anand ◽  
Emmanuel S. Antonarakis ◽  
David M. Nanus ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Predictive Biomarker ◽  
Protein Assay ◽  
Poor Risk ◽  
Hazards Model ◽  
Poor Outcomes ◽  
Taxane Chemotherapy

184 Background: We previously found that men with AR-V7 (+) poor risk mCRPC have a low chance of benefit with abiraterone or enzalutamide. The benefits of subsequent taxane chemotherapy based on AR-V7 status may help inform treatment decisions. Methods: We conducted a multicenter prospective study of men with poor risk mCRPC (PROPHECY, NCT02269982) starting Abi or Enza and subsequent taxane chemotherapy. AR-V7 status from CTCs was assessed before abi/enza and again before taxane chemotherapy using the Epic nuclear protein assay or the Johns Hopkins Adnatest assay. The primary endpoint was to test the association of AR-V7 with radiographic/ clinical progression free survival (PFS) and OS with taxane chemotherapy, using the proportional hazards model, adjusting for Cell Search enumeration and clinical risk score. Results: We enrolled 118 men with mCRPC starting Abi/Enza; of these, 51 were evaluable with CTC AR-V7 testing and received subsequent taxane chemotherapy. With 50 PFS events, see table for final results. While AR-V7 positivity was associated with worse outcomes overall, AR-V7 (+) patients had similar PFS, OS, and confirmed >50% PSA declines adjusting for CTC enumeration and clinical prognostic factors. Concordance between the two AR-V7 assays pre-taxane was 0.78 (kappa 0.46). AR-V7 positivity increased at progression on abi/enza, but not following taxane chemotherapy. Conclusions: Men with AR-V7 positive mCRPC have poor outcomes, but may benefit from taxane chemotherapy after progression on abi/enza. AR-V7 may provide a helpful predictive biomarker to guide treatment with a second AR inhibitor or a taxane. Clinical trial information: NCT02269982. [Table: see text]

Cetuximab plus chemotherapy in patients with liver-limited or non-liver-limited KRAS wild-type colorectal metastases: A pooled analysis of the CRYSTAL and OPUS studies.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 96-96 ◽  
Author(s):  
Claus-Henning Kohne ◽  
Carsten Bokemeyer ◽  
Ute Sartorius ◽  
Michael Schlichting ◽  
Philippe Rougier ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Colorectal Metastases ◽  
R0 Resection ◽  
Wild Type ◽  
Hazards Model

96 Background: In the CRYSTAL and OPUS studies, adding cetuximab (cet) to first-line chemotherapy (CT) improved clinical benefit in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer. In a pooled analysis of these trials the benefit of treatment according to whether pts had liver-limited disease (LLD) or non-LLD was investigated. Methods: Cox‘s proportional hazards model for overall survival (OS) and progression-free survival (PFS) or logistic regression model for objective response rates (ORR) and R0 resection were used on individual pt data, stratified by study. Likelihood ratio tests were used to statistically explore interactions. Results: Adding cet to CT significantly improved PFS and ORR in LLD pts, and OS, PFS and ORR in non-LLD pts ( table ), and increased R0 resection rates: LLD 11.8% vs 5.3%, odds ratio=2.38, p=0.11 and non-LLD, 3.3% vs 1.7%, odds ratio=1.97, p=0.19. No treatment-by-study interactions were noted. Treatment effects did not vary significantly by LLD status (PFS, p=0.60, OS, p=0.68, ORR p=0.074). However LLD vs non-LLD pts had improved outcome in each treatment arm: PFS, CT HR=0.74, p=0.091; CT + cet HR=0.66, p=0.031; OS, CT HR=0.70, p=0.009; CT + cet HR=0.74, p=0.039; ORR, CT odds ratio=1.20, p=0.47, CT + cet odds ratio=2.32, p=0.002; R0 resection, CT odds ratio=3.15, p=0.050, CT + cet odds ratio=3.82, p=0.0018. Conclusions: The OS benefit from adding cet to CT is mainly seen in pts with non-LLD, thus strengthening the value of cet in palliative treatment. LLD status appears to be predictive for response in pts receiving CT + cet, facilitating potential resection. A larger number of pts (with R0 resection and longer follow-up) may be needed to confirm an OS benefit from CT + cet in LLD pts. [Table: see text]

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]

Early carcinoembryonic antigen (CEA) dynamics to predict fruquintinib efficacy in FRESCO, a 3+ line metastatic colorectal carcinoma (mCRC) phase III trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16001-e16001
Author(s):  
Yuxian Bai ◽  
Shukui Qin ◽  
Jin Li ◽  
Yanhong Deng ◽  
Lei Yang ◽  
...  
Keyword(s):  
Placebo Group ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Radiological Evaluation

e16001 Background: The FRESCO phase 3 trial demonstrated a significant survival benefit with fruquintinib vs. placebo in the third-line or later therapy of mCRC patients. CEA levels are widely used in conjunction with imaging to monitor response to systemic therapy in patients with mCRC. Herein, we undertook post-hoc analyses of FRESCO patient data to investigate the early changes in CEA during treatment, as well as potential relationships with efficacy parameters. Methods: Patients were included if baseline CEA was abnormal according to local lab reference range. Serum CEA levels were measured at baseline and Day 1 of each cycle (except for Cycle 1). Early CEA change was analyzed at first radiological evaluation (C3D1, Week 8), CEA response was defined as ≥ 50% decrease from baseline, and CEA progression was defined as ≥ 100% increase from baseline. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated through Cox proportional hazards model; p-value was generated from log rank test. Results: 88.4% (245/277) and 94.9% (130/137) of patients had an abnormal baseline CEA in the fruquintinib group and placebo group, respectively. Median baseline CEA values were similar between treatment groups. After 2 cycles of treatment, the proportion of patients had CEA response was significantly higher in the fruquintinib group than placebo group (30.0% vs. 1.3%, p < 0.001). In the fruquintinib group, patients with early CEA response (n = 63) had longer median OS (12.8 vs. 7.8 months, HR = 0.45, p < 0.001) and median PFS (5.6 vs. 3.7 months, HR = 0.49, p < 0.001) than patients without (n = 147). 66.7% (140/210) of patients in fruquintinib group had stable disease (SD), and fruquintinib in those patients with concomitant CEA response exhibited a significantly greater OS benefit than with CEA progression (14.4 vs. 8.7 months, HR = 0.38, p = 0.004). Conclusions: Fruquintinib increased early CEA response. CEA response at first radiological evaluation after cycle 2 could be considered as a predictor for better OS and PFS. Among patients with SD at first evaluation, those with CEA response seems benefit more from fruquintinib. Clinical trial information: NCT02314819 .

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.

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.

Quality of life (QOL) predicts for progression-free survival (PFS) in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib compared to interferon-alpha (IFN-α)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6594-6594 ◽  
Author(s):  
D. Cella ◽  
J. Z. Li ◽  
J. C. Cappelleri ◽  
A. Bushmakin ◽  
C. Charbonneau ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Self Report ◽  
Phase Iii ◽  
Health State ◽  
Eq Vas

6594 Background: In a recent international, randomized phase III trial, sunitinib malate, an oral multitargeted receptor tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET and FLT3 with both antitumor and antiangiogenic effects, was associated with statistically superior clinical efficacy and superior health-related QOL vs. IFN-a as first-line therapy in patients with mRCC (Motzer et al, Proc ASCO 2006;24:2s [Abstract LBA3]). Here we report a substudy of baseline QOL variables predicting PFS. Methods: 750 mRCC patients were randomized 1:1 to receive either sunitinib 50 mg orally once daily in repeated 6-week cycles (4 weeks on treatment followed by 2 weeks off) or IFN-a (9 MU via subcutaneous injection 3 times weekly). QOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index's Disease-Related Symptoms subscale (FKSI-DRS), and the patient self-rated overall health state (EQ-VAS) from the EuroQol Group's EQ-5D self-report questionnaire. For all QOL endpoints, higher scores indicated better outcomes (better QOL or fewer symptoms). Cox proportional-hazards model was used to test which baseline QOL variables predict PFS while controlling for other baseline demographic and clinical factors as well as treatment. Because the three QOL scores are correlated (r=0.61–0.69), three separate univariate models were fitted. Results and Conclusions: All three baseline QOL variables were predictive of PFS: better baseline FACT-G, FKSI-DRS and EQ-VAS scores were associated with longer PFS. When QOL and other baseline variables were controlled in the models, the superior treatment effect of sunitinib on PFS remained robust and large (See the table below). [Table: see text]

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