Assessment of the association of the VeriStrat test with outcomes in patients (pts) with advanced pancreatic cancer (PC) treated with gemcitabine (G) with or without erlotinib (E) in the NCIC CTG PA.3 phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4061-4061
Author(s):  
Daniel John Renouf ◽  
Wendy Parulekar ◽  
Julia Grigorieva ◽  
Dongsheng Tu ◽  
Malcolm J. Moore
Keyword(s):  
Cox Model ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Drug Benefit ◽  
Phase Iii ◽  
Rank Test ◽  
Phase Iii Trial ◽  
Kaplan Meier ◽  
Pre Treatment

4061 Background: VeriStrat is a mass spectrometry based assay performed on serum or plasma that has been shown to be prognostic in several tumor types, and may predict differential drug benefit in several settings. We investigated the association of VeriStrat with outcomes in the NCIC CTG PA.3 randomized phase III trial of G and E vs. G and placebo (P) in pts with advanced PC. Methods: Pre-treatment plasma samples were available for 499/569 (87.7%) enrolled pts. VeriStrat testing was performed in a CLIA-certified laboratory; pts were classified as either Good, Poor, or indeterminate. The relationship between VeriStrat results and overall survival (OS) and progression free survival (PFS) was assessed by Kaplan-Meier curves and log-rank test in univariate analysis and Cox model adjusting for gender, age [>60 vs. ≤60], race [Caucasian vs. other], ECOG [0-1 vs. 2], and pain intensity at baseline [≤20 vs. >20] in multivariate analysis. The predictive effect was assessed by interaction test. All statistical analyses were performed by the NCIC CTG. Results: Of the 499 samples, 11 were hemolyzed and 4 had acquisition failures. VeriStrat was performed on 484 samples, 9 failed quality control, 22 had indeterminate results. Of the remaining 452, 353 (78%) were classified as Good and 99 (22%) as Poor. In the G and P arm, median OS was 7.16 months (ms) for VeriStrat Good vs. 3.78ms for VeriStrat Poor (p<0.0001); Adjusted Hazard Ratio (AHR) 0.59 (0.43-0.82), p=0.002. In the G and E arm, median OS was 7.33ms for VeriStrat Good vs. 4.50ms for VeriStrat Poor p<0.0001; AHR 0.47 (0.32-0.70), p=0.001. A similar relationship was seen for PFS (G and P arm: median PFS 3.91 vs. 2.07ms (p=0.001); AHR 0.67 [0.49-0.92], p=0.01); G and E arm: median PFS 4.24 vs. 2.86ms (p=0.0004); AHR 0.54 [0.37-0.80], p=0.002). Tests of interaction of VeriStrat status and treatment for OS and PFS were not significant: AHR 0.78 (0.48-1.25), p=0.30 and AHR 0.80 (0.50-1.30), p=0.37 respectively. Conclusions: VeriStrat results were significantly associated with OS and PFS for both regimens in this study. VeriStrat was not predictive of benefit from the addition of E to G.

The predictive role of CA 19–9 kinetics for time-to-progression (TTP) and overall survival (OS) in patients receiving palliative first-line chemotherapy for advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15637-e15637
Author(s):  
M. Haas ◽  
S. Boeck ◽  
P. Stieber ◽  
R. P. Laubender ◽  
H. Buchner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
First Line ◽  
Predictive Role ◽  
Pre Treatment ◽  
Line Chemotherapy

e15637 Background: Previous studies showed contradictory results for a predictive role of CA 19–9 kinetics during chemotherapy in patients (pts) with pancreatic cancer (PC). Methods: We performed a retrospective, multicenter study in order to evaluate the role of CA 19–9 as a biomarker for TTP and OS in PC. Main inclusion criteria: histological confirmed diagnosis of PC, treatment with first-line chemotherapy for advanced disease, pre-treatment CA 19–9 level of > 5.2 U/ml. As CA 19–9 measurements were conducted in different laboratories using different commercial assays, we defined a subgroup of pts where CA 19–9 was assessed exclusively by the Elecsys assay (Roche Diagnostics). For the analysis of CA 19–9 kinetics, at least one follow-up measurement between day 20 and 64 during first-line chemotherapy had to be available. Pts were divided into two subgroups of CA 19–9 responders and non-responders by cut-offs of a 25% and 50% decline, respectively. OS and TTP were estimated with the Kaplan-Meier-Method, differences between the subgroups were analyzed by using the log-rank test. Results: One hundred and eighty-six pts were included, 83 of them were tested with the Elecsys method. Median age was 63 years, 90 % of the pts were treated within prospective clinical trials. Median pre-treatment CA 19–9 was 1076 U/ml (range 5.7–100,000 U/ml), the median bilirubin was 0.6 mg/dl. Median OS and TTP were 9.8 months (mo) and 5.4 mo, respectively. In univariate analysis, pts with a CA 19–9 decline of at least 25% during chemotherapy lived significantly longer (11.9 mo vs. 8.2 mo, p=0.003) and had a significantly prolonged TTP (5.8 mo vs. 4.4 mo, p=0.018) than those with a lower decline or even CA 19–9 increase. Data for the Elecsys-measurements were comparable (OS: 13.4 mo vs. 8.6 mo, p=0.004; TTP: 7.0 mo vs. 2.6 mo, p=0.003). None of the analyses demanding a CA 19–9 drop of at least 50% reached the level of statistical significance. Conclusion: An early CA 19–9 decline of 25% during first-line chemotherapy may predict OS and TTP in pts with advanced PC. Innovative statistical methods are required to improve our understanding of the utility of CA 19–9 as a predictive biomarker in PC. [Table: see text]

An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA7512-LBA7512 ◽  
Author(s):  
G. Scagliotti ◽  
I. Vynnychenko ◽  
Y. Ichinose ◽  
K. Park ◽  
K. Kubota ◽  
...  
Keyword(s):  
Cox Model ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Double Blind ◽  
Grade 3 ◽  
Nonsquamous Nsclc

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]

Comparative study of six cycles versus twelve cycles of adjuvant temozolomide post concurrent chemoradiation in newly diagnosed glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13034-e13034
Author(s):  
Menal Bhandari ◽  
Ajeet K Gandhi ◽  
Pramod Kumar Julka ◽  
Chitra Sarkar ◽  
Dayanand Sharma ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Impact ◽  
Mib 1

e13034 Background: This study assesses the impact of 6 cycles of adjuvant TMZ (conventional arm) versus 12 cycles (Extended arm) on Progression free survival (PFS), evaluate the toxicity and correlate the outcome with EGFR, P53 and MIB I labelling Index. Methods: Between December 2010 to October 2012, 36 post operative patients of Glioblastoma between age 18-65 years and Karnofsky Performance Score (KPS) ≥ 70 were included. Patients were randomized to receive Radiation with a dose of 60 Gray in 30 fractions over 6 weeks at 2 gray/fraction with concomitant TMZ (75 mg/m2/day) and Adjuvant therapy with either 6 or 12 cycles of TMZ(150 mg/m2 for 5 days, 28 days cycle). Patients were then assessed monthly clinically and imaged with MRI/CT every 3 monthly or when symptomatic. Toxicity was assessed using CTCAE version 3.0. Statistical Analysis was done using SPSS version 17.0.Kaplan Meier method was used for analysis of survival and log rank test was used for assessing the impact of variables on survival. Results: Of 36 patients, 18 patients were treated in each arm. Median age and KPS in both the arms was 47 years and 80 respectively. 44 % patients in the conventional arm and 50% patients in the Extended arm underwent complete surgical resection. 22% patients in the conventional arm and 28% in the extended arm did not complete their intended treatment. Grade ¾ Thrombocytopenia was seen in 16% in the extended arm and 0% in the conventional arm.EGFR, P 53 and MIB 1 >20% was seen in 26%, 45% and 20% patients respectively, overall. Median follow up was 18 months for both the arms (Range 10-23 months).At last follow up,8 patients in each arm had progression. Median PFS was 10 months vs.18.4 months (p 0.47) in conventional and extended arm respectively. On Univariate analysis, patients with KPS ≤ 80 had poorer survival than those >80 (Median PFS 9.5 Months vs. 16.9 Months; p 0.02).Age, extent of resection, EGFR, P53, MIB 1 did not significantly alter survival in the two treatment groups. Conclusions: Our study showed that schedule of extended Temozolomide is well tolerated by patients and tend to have better progression free survival. Further prospective randomized studies are needed to validate the findings of our study.

The occurrence of grade 4 adverse events and survival outcomes in patients with nonsquamous non-small cell lung cancer receiving bevacizumab with chemotherapy in the phase III PointBreak and AVAiL studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19022-e19022
Author(s):  
Liza Cosca Villaruz ◽  
Mark A. Socinski ◽  
Jyoti D. Patel ◽  
Larry Leon ◽  
Sebastien Hazard ◽  
...  
Keyword(s):  
Cox Model ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
End Point ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

e19022 Background: Progression-free survival (PFS) is a key trial end point for clinical practice, as it relates to a change of treatment line. Grade 4 progression-free survival (G4PFS; defined as time from treatment start to the earlier of progressive disease [PD], onset of a G4 adverse event [AE], or death from any cause) is a composite end point incorporating a measure of tolerability to PFS. This post hoc analysis evaluates G4PFS and the effect of G4 AEs on PFS and overall survival (OS) in patients (pts) enrolled in PointBreak (PB) and AVAiL. Methods: Pts in PB were randomized to bevacizumab (BEV) 15 mg/kg q3w with carboplatin and paclitaxel (CP) or pemetrexed (CPem) for ≤4 cycles. Eligible pts received either BEV or BEV + Pem q3w until PD or unacceptable toxicity. Pts in AVAiL received cisplatin and gemcitabine for ≤6 cycles and either placebo or BEV (7.5 or 15 mg/kg) q3w until PD. AEs were graded via NCI-CTCAE v3.0. Kaplan-Meier and Cox model methods were used to estimate medians and hazard ratios (HRs) for PFS, G4PFS, and OS. PFS and OS were also compared in each arm for pts with occurrence of a G4 AE before week 12 of treatment vs those without. Results: Of those receiving BEV, ~30% of AVAiL pts and 38% of PB pts had a G4 AE. Uncomplicated neutropenia was the most common G4 AE in the CP + BEV arm of PB (26%) and in the BEV arms of AVAiL (11%). PFS, G4PFS, and outcomes by G4 AE occurrence are shown (Table). Conclusions: In both the PB and AVAiL trials, median G4PFS was numerically shorter than median PFS. G4 AE occurrence, however, did not affect subsequent PFS or OS in either trial. Clinical trial information: NCT00762034 and NCT00806923. [Table: see text]

Factors influencing survival in inflammatory breast cancer.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 136-136
Author(s):  
Julie A. Cupp ◽  
Diane Liu ◽  
Yu Shen ◽  
Naoto T. Ueno ◽  
Ricardo H. Alvarez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Poor Prognosis ◽  
Cox Model ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Rapid Progression ◽  
Progression Of Disease ◽  
Delay In Treatment

136 Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer associated with poor prognosis, characterized by rapidly growing mass, skin changes, and regional adenopathy. The objective of this study was to determine if delay in treatment influenced survival in IBC patients. Methods: A prospective IBC database identified 93 women with stage III IBC who received care at MD Anderson from 2007 - 2012 and were retrospectively reviewed. All patients received neoadjuvant chemotherapy followed by surgery, unless progression of disease was noted, and postmastectomy radiation. Impact of time from onset of symptoms to chemotherapy or to surgery on overall survival (OS) and progression free survival (PFS) were evaluated after adjusting for the baseline covariates in the Cox model. Results: A majority of patients were white (77.4%) with an average age of 54 years. Average days from onset of symptoms to first chemo is 95 (range 16 – 387) and to surgery is 283 (range 184 – 585). Four patients had progression while on chemo. There were 14 deaths with median follow up of 2.6 years from diagnosis. In univariate analysis, delay in treatment, > 90 days from onset of symptoms to chemo, did not affect OS or PFS. Obtaining negative margins was statistically significant for OS and PFS measured from first chemo (p=0.005 and p=0.007). Positive HER-2 status was associated with longer PFS time from chemo (p=0.02, log-rank test) and from surgery (p=0.009). Positive progesterone receptor (PR) was found to be statistically significantly associated with longer OS time from chemo (p=0.01) and from surgery (p=0.03). Clinical and imaging response to chemo were associated with better OS (p=0.007 and p=0.005) and pathologic response was marginally associated with improved OS and PFS (p=0.07 and p=0.06), both measured from surgery. In multivariate Cox model, adjusting for PR or HER2, days from onset of symptoms to chemo or surgery did not have significant impact on OS or PFS. Conclusions: While traditionally delay diagnosis and treatment is considered one of the factors associated with poor prognosis, our study suggests otherwise. However, due to such rapid progression of disease, early diagnosis is still important in the overall management of patients diagnosed with IBC.

AURELIA: A randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA5002-LBA5002 ◽  
Author(s):  
Eric Pujade-Lauraine ◽  
Felix Hilpert ◽  
Béatrice Weber ◽  
Alexander Reuss ◽  
Andres Poveda ◽  
...  
Keyword(s):  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Phase Iii ◽  
Rank Test ◽  
Meaningful Improvement ◽  
Phase Iii Trial ◽  
Phase Iii Trials ◽  
History Of

LBA5002^ Background: In three phase III trials in OC (2 front line, 1 PT-sensitive recurrent), BEV + CT → BEV significantly improved progression-free survival (PFS) vs CT alone. AURELIA is the first randomized trial of BEV in PT-resistant OC. Methods: Eligible patients (pts) had OC (measurable by RECIST 1.0 or assessable) that had progressed ≤6 mo after ≥4 cycles of PT-based therapy. Pts with refractory OC, history of bowel obstruction, or >2 prior anticancer regimens were ineligible. After CT selection by the investigator (pegylated liposomal doxorubicin [PLD], topotecan [TOP], or weekly paclitaxel [PAC]), pts were randomized to CT either alone or with BEV (10 mg/kg q2w or 15 mg/kg q3w depending on CT) until progression (PD), unacceptable toxicity, or withdrawal of consent. Pts in the CT-alone arm could cross over to BEV monotherapy at PD. The primary endpoint was PFS by RECIST. Secondary endpoints included objective response rate (ORR), overall survival, safety, and quality of life. The design provided 80% power to detect a PFS hazard ratio (HR) of 0.7 with 2-sided log-rank test and α=0.05 after 247 events, assuming median PFS of 4.0 mo with CT and 5.7 mo with CT + BEV. Results: Between Oct 2009 and Apr 2011, 361 pts were randomized to receive selected CT (PLD: 126; PAC: 115; TOP: 120) alone or with BEV. Median follow-up after 301 PFS events was 13.5 mo. Conclusions: In PT-resistant OC, BEV + CT provides statistically significant and clinically meaningful improvement in PFS and ORR vs CT alone. Strict inclusion criteria minimized the incidence of BEV AEs. This is the first phase III trial in PT-resistant OC to show benefit with a targeted therapy and improved outcome with a combination vs monotherapy. [Table: see text]

The biomarkers of gemcitabine and erlotinib treatment in advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 358-358
Author(s):  
Kuniyasu Irie ◽  
Makoto Ueno ◽  
Satoshi Kobayashi ◽  
Yoshihiro Gouda ◽  
Shinichi Ohkawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Multivariate Analysis ◽  
Performance Status ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Rank Test ◽  
Antiulcer Drugs ◽  
The Difference

358 Background: A combination of gemcitabine+erlotinib is one of the standard chemotherapies in advanced pancreatic cancer (APC). Since APC patients often take antiulcer drugs to prevent gastritis (e.g., NSAIDs to reduce cancer pain), erlotinib concentration is generally decreased through the mechanism of CYP3A4. Furthermore, unlike lung cancer, the biomarkers for APC are not obvious except rash. Here, we examined biomarkers of gemcitabine+erlotinib treatment in APC patients including the presence of antiulcer drugs. Methods: The subjects were 59 advanced pancreatic cancer patients. They were treated with gemcitabine+erlotinib starting from Nov. 2011 to Apr. 2013. Gemcitabine was administered at 1000 mg/m2, on days 1, 8, and 15 for every 4 weeks, and erlotinib was taken 100 mg daily. The progression-free survival (PFS), UICC stage, sex, age, CRP concentration, performance status (PS), rash, and presence of antiulcer drugs were examined. The PFS curve was plotted according to the method of Kaplan and Meier. The difference in the PFS was calculated using the log-rank test, and a multivariate analysis was conducted using Cox hazard model. Results: UICC stages were as follows; i.e., stage II: 1, stage III: 8, and stage IV: 50. There were 36 males and 23 females, and their ages ranged from 41 to 82 years old (median: 65). The CRP concentrations ranged from 0.02 to 11.5 mg/dl (median: 0.57). 37 patients received antiulcer drugs, and 48 patients had rash. The univariate analysis revealed that the CRP concentration and rash were significant (p=0.009 and p=0.005, respectively). Low CRP (<0.57mg/dl) and presence of rash were related to good PFS. The multivariate analysis also revealed that the CRP concentration (HR, 0.34; 95%CI, 0.16-072; p=0.005) and rash (HR, 0.40; 95%CI, 0.16-0.96; p=0.04) were significant. The presence of antiulcer drugs on PFS was insignificant. Conclusions: The CRP concentration and rash were biomarkers of gemcitabine+erlotinib treatment in APC patients.

TAS-118 (S-1 plus leucovorin) versus S-1 in gemcitabine-refractory advanced pancreatic cancer: A randomized, open-label, phase III trial (GRAPE trial).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4099-4099 ◽  
Author(s):  
Makoto Ueno ◽  
Tatsuya Ioka ◽  
Hideki Ueno ◽  
Joon Oh Park ◽  
Heung-Moon Chang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Primary Endpoint ◽  
Pancreatic Resection ◽  
Treatment Effects ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Oral Drug ◽  
Open Label ◽  
Phase Iii Trial

4099 Background: Addition of oral leucovorin (LV) to S-1 significantly improved progression-free survival (PFS) in a previous randomized phase II trial in Japanese patients (pts) with gemcitabine (GEM)-refractory advanced pancreatic cancer (PC). TAS-118 is an oral drug containing S-1 and LV. This phase III trial conducted in Japan and Korea compared overall survival (OS) between GEM-refractory advanced PC pts treated with TAS-118 and S-1. Methods: GEM-refractory PC pts were randomized in a 1:1 ratio to receive TAS-118 (S-1; 40-60 mg and LV; 25 mg bid for 1w, q2w) or S-1 (S-1; 40-60 mg bid for 4w, q6w). The primary endpoint was OS. The secondary endpoints included PFS, overall response rate, disease control rate, duration of response, and safety. Results: Five hundred and eighty-six pts were eligible for efficacy assessment (TAS-118: n=296 and S-1: n=290). Baseline characteristics were well balanced between the treatment arms. TAS-118 did not result in a statistically significant improvement in OS compared with that achieved with S-1 (median OS, 7.6 months vs. 7.9 months; hazard ratio [HR], 0.98; 95% CI, 0.82 to 1.16; P=0.756). However, it significantly improved PFS compared to that achieved with S-1 (median PFS, 3.9 months vs. 2.8 months; HR, 0.80; 95% CI, 0.67 to 0.95; P=0.009). Pre-planned subgroup analysis of OS showed significant interactions between the treatment effects and pancreatic resection (P=0.025), and between the treatment effects and country (P=0.004). Grade 3/4 drug-related adverse events (≥5% incidences) in TAS-118 and S-1 arms included diarrhea (7.0% vs. 7.3%), anorexia (6.7% vs. 5.0%), stomatitis (6.7% vs. 0.7%), and anemia (3.3% vs. 5.0%). Conclusions: The primary endpoint was not met. Further, the interactions between the treatment effects and pancreatic resection, and between the treatment effects and country, might affect the results. Clinical trial information: 132172. [Table: see text]

Dacomitinib versus gefitinib for the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer (ARCHER 1050): A randomized, open-label phase III trial.

2017 ◽  
Vol 35 (18_suppl) ◽  
pp. LBA9007-LBA9007 ◽  
Author(s):  
Tony Mok ◽  
Ying Cheng ◽  
Xiangdong Zhou ◽  
Ki Hyeong Lee ◽  
Kazuhiko Nakagawa ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Cox Model ◽  
Objective Response ◽  
Phase Iii ◽  
Rank Test ◽  
Meaningful Improvement ◽  
Phase Iii Trial ◽  
Line Therapy ◽  
Patient Reported ◽  
Activating Mutation

LBA9007 Background: Dacomitinib is a 2nd generation EGFR TKI with encouraging clinical activity as 1st-line therapy in patients with EGFR-activating mutation positive advanced NSCLC (Jänne, Lancet Oncol 2014). We performed the first randomized phase III trial, currently ongoing, comparing dacomitinib (D) with gefitinib (G) as 1st-line therapy (1L) (NCT01774721). Methods: Patients (pts) with newly diagnosed stage IIIB/IV/ recurrent NSCLC harboring an EGFR- activating mutation (exon 19 del or exon 21 L858R mu +/- exon 20 T790M mu) were randomized 1:1 to D 45 mg PO QD or G 250mg PO QD; stratification was by race and EGFR mutation subtype. The primary endpoint was PFS per blinded independent review (IRC) analyzed by Kaplan-Meier method with log-rank test and Cox model. Secondary endpoints included: overall survival, objective response rate (ORR), duration of response (DR), PFS per Investigator (INV), time to treatment failure (TTF), restricted mean survival time (RMST) for PFS, safety and patient-reported outcomes (PROs). Results: The ITT population included 452 pts with baseline characteristics fairly well balanced between the arms. ORR per IRC was similar between arms (75% [95% CI: 69, 80] for D and 72% [95% CI: 65, 77]; 2-sided p-value = 0.39; OS is not mature. The most commonly reported grade 3 adverse events with dacomitinib were dermatitis acneiform (13.7%) and diarrhea (8.4%) and with gefitinib ALT (8.5%); no new safety signals were identified. Conclusions: ARCHER 1050 was the first phase III head-to-head study of EGFR TKIs and demonstrated statistically significant and clinically meaningful improvement in efficacy of D vs. G in 1L NSCLC pts with EGFR-activating mutations with a manageable safety profile, to offer a new 1L treatment option. Clinical trial information: NCT01774721. [Table: see text]

Multicentric prospettive study of validation of angiogenesis-related gene polymorphisms in hepatocellular carcinoma patients treated with sorafenib: Interim analysis of INNOVATE study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4075-4075
Author(s):  
Andrea Casadei Gardini ◽  
Giorgia Marisi ◽  
Vincenzo Dadduzio ◽  
Luca Faloppi ◽  
Luca Ielasi ◽  
...  
Keyword(s):  
Prospective Study ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Meld Score ◽  
Rank Test ◽  
Event Time ◽  
Kaplan Meier ◽  
Clinical Covariates ◽  
A Prospective Study

4075 Background: In the ePHAS study we analyzed three eNOSpolymorphisms and at univariate analysis, patients with eNOS-786 -TTgenotype had significantly shorter median Progression Free Survival (PFS) and Overall Survival (OS) compared to those with other genotypes. On the basis of these preliminary results, our aim is to validate in a prospective study this data in patients with HCC treated with sorafenib. Methods: This is a prospective Italian multicenter study, that includes 141 HCC patients receiving sorafenib. We analyzed eNOS-786and itwas analyzed by Real Time PCR in relation to the primary end point (OS). Event-time distributions were estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. Results: 141 HCC patients (122 males and 19 females), prospectively treated with sorafenib from May 2015 to September 2018 were included. Median age was 69 years (range 28-88 years). 120 patients had Child-Pugh A and 21 had Child-Pugh B7. 43 had BCLC-B and 98 patients had BCLC-C. Atunivariate analysis, we confirmed that eNOS-786 TT genotype were significantly associated with a lower median OS than the other genotypes (8.8 vs 15.7 months, HR 1.69, 95% CI 1.02-2.83 p=0.0424). Following adjustment for clinical covariates (age, gender, etiology, BCLC stage, serum α-FP level, MELD score), multivariate analysis confirmed eNOS- 786 and BCLC stage as the independentsprognostic factors predicting OS (TTvsTC+CC; HR: 2.39, 95% CI 1.14-5.03 p=0.0211; C vs B;2.23, 95% CI 1.44-4.77 p=0.039). Conclusions: Our prospective study confirms the prognostic role of eNOS-786 in advanced HCC patients treated with sorafenib. Clinical trial information: NCT02786342.

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