Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA4509-LBA4509 ◽  
Author(s):  
P. A. Philip ◽  
J. Benedetti ◽  
C. Fenoglio-Preiser ◽  
M. Zalupski ◽  
H. Lenz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Clinically Significant

LBA4509 Background: Epidermal growth factor receptor [EGFR] pathway is a rational target for therapeutic intervention. This study tested the efficacy of an anti-EGFR monoclonal antibody and gemcitabine [G] combination in the Phase III setting in patients with advanced PC. Methods: Eligibility included locally advanced unresectable or metastatic PC; adequacy of organ function; performance status (PS) 0- 2; no prior EGFR therapy; no prior systemic chemotherapy except for adjuvant chemotherapy; and submission of tumor for EGFR immunostaining. The primary endpoint was overall survival. Secondary endpoints included objective response, time to progression, pain control, and quality of life. Assuming 6 months median survival, the study was designed to detect a median improvement to 8 months (1.33 hazard ratio) with 90% power, based on a one-sided 0.0125 test, and 704 eligible patients. Primary analyses used a Cox regression model, stratified for factors used in the randomization. Patients were stratified by PS, stageand prior pancreatectomy, and randomized to either G alone or G plus C. G was given at a dose of 1,000 mg/m2/wk for seven weeks out of 8, then 3 weeks on and one week off. C was given as a loading dose of 400 mg/m2 on week 1 and then 250 mg/m2 weekly. Results: 766 pts (735 eligible) with a median age of 64 (30–91) were enrolled by SWOG and CTSU between January 2004 and April 2006. Of those, 51% were males, 21.5% had locally advanced disease, and 13% had PS of 2. The study closed with full accrual. The median survival was 6 months in the G arm and 6.5 months in the G plus C arm for an overall HR of 1.09 (95% CI 0.93–1.27, p= 0.14) . The corresponding PFS was 3 months and 3.5 months, for G and G+C arms, respectively (HR =1.13, 95%CI .97–1.3, p=.058). The confirmed response probabilities were 7 % in each arm, and inclusion of unconfirmed responses yielded 14% in the G arm and 12% in the G + C arm.702 pts were evaluable for toxicity. 90 pts experienced at least one grade 4 toxicity; 14% on the G plus C, 11% on G alone. Conclusions: This study failed to demonstrate a clinically significant advantage of the addition of cetuximab to gemcitabine for overall survival, PFS and response in advanced PC. No significant financial relationships to disclose.

scholarly journals 312 Female sex independently predicts adjuvant immunotherapeutic benefit from CTLA4 immune checkpoint inhibition

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A339-A339
Author(s):  
Ahmad Tarhini ◽  
Ni Kang ◽  
Sandra Lee ◽  
F Stephen Hodi ◽  
Gary Cohen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Efficacy ◽  
Significant Interaction ◽  
Cox Regression ◽  
Performance Status ◽  
Phase Iii ◽  
High Dose ◽  
List Type ◽  
Female Sex ◽  
Interaction Term

BackgroundSex differences in tumor immunity and response to immunotherapy were shown in murine models and descriptive analyses from recent clinical trials. Female sex hormones have been implicated in melanoma development and response to systemic therapy. We hypothesized a gender difference in response to adjuvant immunotherapy with ipilimumab (3 or 10 mg/kg; ipi3 or ipi10) versus high dose IFNα (HDI) as tested in the E1609 trial.MethodsE1609 demonstrated significant overall survival (OS) benefit with ipi3 versus HDI.1 We investigated treatment efficacy between ipi and HDI in the subgroups by sex (female, male), age (< 55 or ≥55), stage at study entry (IIIB, IIIC, M1a/1b), ECOG performance status (PS 0, 1), ulceration (yes, no), primary tumor (known, unknown), number of lymph nodes involved (0, 1, 2–3, 4+). Forest plots were created to compare OS and RFS with ipi3 vs. HDI and ipi10 vs. HDI using the concurrently randomized ITT populations. For the estimated HRs, 95% confidence intervals were created for all subgroups.ResultsThe subgroups of female, stage IIIC, PS=1, ulcerated, in-transit without lymph node involvement demonstrated significant improvement in overall survival (OS) and/or relapse free survival (RFS) with ipi3 versus HDI as summarized in table 1. Female sex was significant for both OS and RFS and was further explored. In investigating RFS with ipi3 versus HDI, a multivariate Cox regression model including sex, treatment and interaction term of sex*treatment, indicated a significant interaction between sex and treatment (P = 0.026). Including sex, PS (0 vs. 1), age (<55 vs. 55+), ulceration (yes vs. no), stage (IIIB, IIIC, M1a, M1b), treatment and interaction term of sex*treatment, indicated a significant interaction between sex and treatment (P = 0.024). While similar trends were seen, no significant interactions between sex and treatment effect were found in the OS multivariate analysis or in the comparison of ipi10 versus HDI. When exploring age, in the univariate analyses in the ipi3 versus HDI comparison older women appeared to drive most of the difference (age ≥55: OS, P=0.02 and RFS, P=0.08; differences non-significant for women <55). Table 1.Abstract 312 Table 1Treatment efficacy between ipi3 and HDI by subgroupConclusionsFemale sex was independently associated with RFS adjuvant immunotherapeutic benefit from ipi3, supporting a potentially important role for female related factors in the immune response against melanoma, and these warrant further investigation.Trial RegistrationNCT01274338Ethics ApprovalThe study protocol was approved by the institutional review board (IRB) of each participating institution and conducted in accordance with Good Clinical Practice guidelines as defined by the International Conference on Harmonisation. This study was monitored by the ECOG-ACRIN DataSafety Monitoring Committee and the NCI.ConsentAll patients provided IRB-approved written informed consent.ReferenceTarhini AA, Lee SJ, Hodi FS, Rao UNM, Cohen GI, Hamid O, Hutchins LF, Sosman JA, Kluger HM, Eroglu Z, Koon HB, Lawrence DP, Kendra KL, Minor DR, Lee CB, Albertini MR, Flaherty LE, Petrella TM, Streicher H, Sondak VK, Kirkwood JM. Phase III Study of Adjuvant Ipilimumab (3 or 10 mg/kg) Versus High-Dose Interferon Alfa-2b for Resected High-Risk Melanoma: North American Intergroup E1609. J Clin Oncol. 2020 Feb 20;38(6):567–575. PMID: 31880964.

A randomized comparison of carboplatin/vinorelbine versus carboplatin/gemcitabine in advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7033-7033
Author(s):  
N. Helbekkmo ◽  
S. H. Sundtroem ◽  
U. Aaseboe ◽  
P. F. Brunsvig ◽  
C. L. Von Plessen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year

7033 Background: Carboplatin/vinorelbine (CV) and carboplatin/gemcitabine (CG) are novel 2-drug combinations in the treatment of NSCLC. In a randomized national multicenter phase III study in stage IIIB and IV patients (pts), we compared these regimens with respect to efficacy, toxicity and quality of life (QoL). Methods: Chemonaive pts with histologically or cytologically proven NSCLC, stage IIIB or IV and ECOG performance status (PS) 0–2 were eligible. There was no upper age limit. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2, both administered on day 1 and 8, in combination with carboplatin (Chatelut AUC 4) at day 1. Three courses were administered in 3-week cycles. QoL questionnaires were completed at baseline, before each cycle and then every 8 weeks up to one year. Primary endpoints were survival and QoL and secondary endpoints toxicity and time to progression (TTP). Stratification was done for age, stage and PS, and the planned sample size per arm was minimum 200. The analyses were performed on an intention-to-treat basis Results: From Oct 2003 through Dec 2004, 433 pts from 33 institutions were randomized to CV (n=218) or CG (n=215). Follow-up was minimum one year. There was no difference in overall survival between the two arms (p=0.89). Median survival was 7.3 vs. 6.5 months and 1-year survival 28% and 31% in the CV and CG arm respectively. TTP was significantly longer in the CG arm (p=0.006) with median TTP 4.2 vs. 3.9 months. There was significantly more grade 3–4 anemia and thrombocytopenia in the CG arm (p<0.001) and more grade 3–4 leucopenia in the CV arm (p= 0.001). More pts in the CG arm needed transfusions of blood (p=0.003) or platelets (p=0.001). There was no difference between the arms with respect to neutropenic infections (p=0.87). QoL data are still being analyzed and will be presented at ASCO. Conclusions: Overall survival was similar in the two treatment arms. In the CG arm, the median TTP was longer, but grade 3–4 toxicity requiring interventions, was more frequent when compared to the VC arm. No significant financial relationships to disclose.

Cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil (5-FU) in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R&M SCCHN) (EXTREME)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5537-5537 ◽  
Author(s):  
J. B. Vermorken ◽  
R. Mesia ◽  
M. E. Vega-Villegas ◽  
E. Remenar ◽  
R. Hitt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Prognostic Significance ◽  
Safety Data ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Safety Analysis ◽  
Data Safety Monitoring Board ◽  
Phase Iii

5537 Background: The epidermal growth factor receptor (EGFR) is expressed in nearly all SCCHN and carries a strong prognostic significance, providing the rationale for using EGFR-targeted agents, such as cetuximab, in this indication. This study assesses the efficacy and safety of cetuximab in combination with chemotherapy commonly used in the treatment of R&M SCCHN. Methods: Patients (pts) were enrolled into this phase III trial from December 2004 to December 2005 and randomized either to Group A: cetuximab (first dose 400 mg/m2 then 250 mg/m2 weekly) plus a maximum of 6 three-weekly cycles of cisplatin (100 mg/m2 IV on day 1) or carboplatin (AUC 5, day 1) and 5-FU (1000 mg/m2/day continuous infusion for the first 4 days of each cycle) or to Group B: cisplatin or carboplatin with 5-FU as before. Cetuximab was administered until progression or unacceptable toxicity. Primary endpoint is overall survival time; secondary endpoints are progression-free-survival, response rate, disease control rate, safety, and Quality of Life. It was planned to randomize a total number of 420 pts in order to detect a difference in improvement in overall survival of 2.5 months. Results: At the end of the recruitment,440 pts have been randomized, to date 320 pts are under treatment, 21 have withdrawn from the study and 99 have completed the study. The Data Safety Monitoring Board (DSMB) has performed an independent preplanned safety analysis from the first 140 pts, 138 pts of whom were treated. Patients were followed for a minimum of 6 weeks: M/F122/16, median age57 years [range, 38–79],median Karnofsky performance status (KPS) 80 [range, 70–100]. In this safety analysis, there were 14 deaths, none of which were treatment related. The most frequent drug related grade 3–4 toxicity was mainly represented by neutropenia, thrombocytopenia and anemia. Conclusions: The DSMB evaluated baseline and safety data, found no reason to stop the trial and recommended continuation of the study. [Table: see text]

A novel intermediate endpoint for predicting overall survival in men with metastatic castration-recurrent prostate cancer (CRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5113-5113 ◽  
Author(s):  
S. Halabi ◽  
S. Ou ◽  
N. J. Vogelzang ◽  
H. Scher ◽  
E. J. Small
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Clinical Benefit ◽  
Opioid Analgesic ◽  
Performance Status ◽  
Phase Iii ◽  
Training Dataset ◽  
Survival Times ◽  
Androgen Ablation ◽  
Three Components

5113 Background: In this proposed study, we developed and validated a novel composite clinical benefit endpoint constructed from symptoms that have intrinsic clinical importance in 800 men with CRPC who were treated with front-line chemotherapy. Methods: Data from nine multimember trials (five phase II and four randomized phase III studies) conducted by the Cancer and Leukemia Group B (CALGB) from 1992–2004 were combined. Eligible patients had progressive adenocarcinoma of the prostate during androgen ablation (despite castrate testosterone levels), an ECOG performance status of 0–2, adequate hematologic, renal and hepatic functions. The tripartite composite clinical benefit endpoint (TCCBE) had three components: one based on disease progression (whether it be PSA, bone, or soft tissue progression), and the second based on weight loss (defined as at least 10% decline from baseline) or on performance status (PS) decline (by at least one level) to capture clinical deterioration. The third component was based on pain control and opioid analgesic use (no or yes). For a person to fall in the TCCBE “yes” category, at least two of the three components had to be recorded as no. For instance, if a patient at 3 months had no progression, no change in weight and did not use opioid analgesic, then he will be classified in the “yes” group and for the purpose of this analysis was considered as someone who achieved “clinical benefit”. The sample was randomly split into 526 (67%) and 274 (33%) men in the training and testing datasets, respectively. Results: From the training dataset, the median survival times in men who had and did not have clinical benefit were 20.9 months (95% confidence interval (CI) = 18.5–22.8) and 11.1 months (95% = 8.79–12.6, p- value<0.001). In the testing dataset, the median survival times in men with and without clinical benefit were 21.7 months (95% CI= 19.1–26.1) and 8.8 months (95% CI= 7.8–11.6) and in men. The hazard ratio (HR) for men with a clinical benefit compared to men without was 0.52 (95% CI= 0.43–0.62, P<0.001). Conclusions: The TCCBE is a statistically significant intermediate endpoint for predicting overall survival. Prospective validation of this endpoint is needed. No significant financial relationships to disclose.

A randomized phase III study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable and metastatic pancreatic cancer (PC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4601-4601 ◽  
Author(s):  
T. Buanes ◽  
J. Maurel ◽  
W. Liauw ◽  
M. Hebbar ◽  
J. Nemunaitis
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Locally Advanced ◽  
Peptide Vaccine ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Delayed Treatment ◽  
Sequential Combination ◽  
The Impact

4601 Background: A phase I/II study with GV1001, a telomerase peptide vaccine, showed a median overall survival (OS) of 8.6 months in non-resectable PC (Bernhardt SL et al, Br J Cancer. 2006;95:1474–1482). This phase III trial was conducted to determine the impact on overall survival of G monotherapy vs. GV1001 in sequential combination with G in unresectable and metastatic PC. Methods: Eligible patients (pts) had chemotherapy-naive, advanced PC and ECOG performance status 0–1. Pts were randomized 1:1 to receive arm A: G (1,000 mg/m2 30 min i.v.) weekly for 7 weeks (w), 1w off and then 3w during 4-weekly cycles, or arm B: GV1001 0.56 mg s.c. plus GM-CSF as immune adjuvant on days 1, 3, 5, 8, 15, 22, 36, then every 4 weeks. Patients who progressed clinically or radiologically during GV1001 continued on GV1001 and concomitant gemcitabine. CT scans were performed every 8 weeks. The primary end-point was OS. A sample size of 520 patients allowed the detection of a hazard ratio (HR) of 0.73 (B/A), with 2α = 0.05 and 90% power. Results: Between June 2006 and May 2008, 365 pts were enrolled (A / B; 182 / 183). The study was stopped prematurely due to a preliminary analysis with 178 events showing no survival benefit of GV1001. Pts were well balanced for baseline characteristics: male 59.3% / 62.8%; median age 61y / 61y; ECOG PS 0 34.3% / 36.7%; locally advanced 22.4% / 20.7%. As of August 2008, 238 pts (A / B : 114 / 124) had died. Median OS was 7.3 / 5.9 months (HR 0.8; 95% CI 0.6–1.0). Median progression-free survival (PFS) was 3.7 / 1.9 months (HR 0.5; 95%CI 0.4–0.7). Grade 3–4 AEs: gastrointestinal 6% / 8%, infection 5% / 5%, vascular disorders 2% / 3%, neutropenia 6% / 3%. Conclusions: GV1001 did not show efficacy in sequential combination with G in advanced PC. The advantage of G monotherapy over the sequential combination may be due to the delayed treatment with G in arm B. [Table: see text]

SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P) with or without cetuximab (C) in recurrent or progressive non-small cell lung cancer (NSCLC) after platinum-based therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7502-7502 ◽  
Author(s):  
Edward S. Kim ◽  
Marcus A. Neubauer ◽  
Allen Lee Cohn ◽  
Lee Steven Schwartzberg ◽  
Lawrence E. Garbo ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Duration Of Response ◽  
Independent Review ◽  
Secondary Endpoints

7502 Background: SELECT investigated whether the addition of C to standard chemotherapy improved progression-free survival (PFS) in patients (pts) with recurrent or progressive NSCLC after failure of platinum-based therapy. Methods: SELECT was a multicenter, open label, randomized phase III trial. Per investigator choice, pts received either P (500 mg/m2) or D (75 mg/m2) on day 1 and then were randomized within each group to chemotherapy plus C (400/250 mg/m2) (initial/weekly) or chemotherapy alone. Therapy was given for up to six 3-week cycles; pts randomized to C continued weekly monotherapy until disease progression or unacceptable toxicity. The primary objective was PFS for PC vs. P as determined by an Independent Review Committee (IRC). Secondary endpoints included overall survival (OS), objective response rate (ORR) and duration of response (DOR) by IRC, and safety. Preplanned subgroup analyses for epidermal growth factor receptor (EGFR) staining intensity by immunohistochemistry and histology were performed. Results for PC vs. P only are presented. Results: Between Jan 2005 and Feb 2010, 938 total pts were randomized. Baseline demographics were comparable between PC (n=301) and P (n=304): median age 64 years; male 60%; Caucasian 88%; KPS 80-100/60-70 84%/16%; squamous/non-squamous 24%/76%. Median PFS (months) PC: 2.89 and P: 2.76 (hazard ratio [HR] =1.03 [95% confidence interval (CI)=0.87-1.21]; p=0.76). Median OS (months) PC: 6.93 and P: 7.79 (HR=1.01 [95% CI=0.86-1.20]; p=0.86). ORR PC: 6.6% and P: 4.3% (odds ratio =1.59 [95% CI=0.78-3.26]; p=0.20). Median DOR (months) PC: 4.17 and P: 6.93 (HR=1.58 [95% CI=0.74-3.36]; p=0.24). There were no statistical differences in efficacy based on histology or EGFR staining intensity. More drug-related AEs/SAEs were observed in the PC arm, with differences mainly attributable to skin toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. Conclusions: The addition of C to P did not improve efficacy in this pt population. Further biomarker analyses are planned. The safety profiles for C and P were consistent with existing data and no new safety signals were observed.

Activity and survival benefit of second-line chemotherapy (2L-Ctx) in advanced pancreatic adenocarcinoma (APC): Pooled analysis of the literature.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15019-e15019 ◽  
Author(s):  
MinYuen Teo ◽  
Raymond S. McDermott
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Survival Benefit ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Setting ◽  
Line Chemotherapy

e15019 Background: Many clinicians adopt a nihilistic approach to the management of APC. Delivery of 2L-Ctx is relatively uncommon and no recognized standard exists. We sought to examine the published activity of chemotherapy in the 2nd line setting, and the rate of 2L-Ctx delivery and its influence on reported overall survival in 1st line trials. Methods: 1st and 2L-Ctx randomized trials published between 2000 and 2012 were identified from Pubmed, and manuscripts were obtained for data extraction. Pooled weighted objective response rates (ORR) and disease control rates (DCR) were calculated. For 1st line studies, the percentage of patients who received 2L-Ctx were extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Spearman correlation and linear regression were performed. Results: Sixty nine 2L Ctx studies (77 arms, n=2859) were identified. Majority received prior gemcitabine-based chemotherapy. Pooled ORR was 6.6% (95% CI 5.6 – 7.6%) and DCR was 36.7% (34.5 – 38.0%). When only prospective studies were evaluated (42 studies, 48 arms, n=1546), ORR was 5.0% (3.8 – 6.2%) and DCR was 33.9% (31.0 – 36.9%). Exploratory analysis suggested that intensification of gemcitabine-based therapy (ORR: 10.0%; DCR: 54.7%) might be marginally more active than fluoropyrimidine (7.6%; 32.2%) or taxane based 2L-Ctx (5.2%; 33.6%). 28/52 identified 1st line studies (54%) reported the percentage of patients treated with second-line chemotherapy (11 phase II, 28 arms, n=1450; 17 phase III, 33 arms, n=5051). Percentage of 2L-Ctx delivery ranged from 14 – 68% and correlated with OS (r=.49 [.26 – .67], p<.01) and PPS (r=.57 [.36 – .72], p<.01). When phase II studies were excluded, correlation was improved for OS (r=.63 [.35 – .81], p<.01) and PPS (r=.79 [.59 – .89], p<.01). Percentage of locally advanced disease did not correlate with OS/PPS nor affect prior analysis. Conclusions: Whilst awaiting further advancement in the 1st line setting, increased delivery of 2L-Ctx to patients with APC and maintained performance status may offer a survival benefit.

Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer

2009 ◽  
Vol 27 (33) ◽  
pp. 5513-5518 ◽  
Author(s):  
David Cunningham ◽  
Ian Chau ◽  
Deborah D. Stocken ◽  
Juan W. Valle ◽  
David Smith ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Primary Outcome Measure ◽  
Phase Iii ◽  
Open Label

PurposeBoth gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).Patients and MethodsPatients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.ResultsBetween May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.ConclusionOn the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.

Analysis of prognostic factors in patients with advanced relapsed/refractory NSCLC: Cox regression analysis of a randomized phase III trial comparing docetaxel and paclitaxel poliglumex (PPX)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7040-7040 ◽  
Author(s):  
P. Bonomi ◽  
C. Langer ◽  
M. O’Brien ◽  
K. O’Byrne ◽  
B. Bandstra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Stage Iv ◽  
Tumor Stage ◽  
Phase Iii ◽  
Line Treatment ◽  
Phase Iii Trial ◽  
Cox Regression Analysis ◽  
The Impact

7040 Background: A phase III trial compared PPX to docetaxel as 2nd-line treatment in pts with relapsed/refractory advanced NSCLC (STELLAR 2). While overall survival was similar between arms, the need for supportive measures to manage the effects of myelosuppression was significantly reduced in the PPX arm. The current analysis was performed to evaluate determinants of survival in the 2nd-line treatment of NSCLC. Methods: STELLAR 2 enrolled 849 pts, 427 on PPX and 422 on docetaxel; all patients were included in the analysis. Randomization between the study arms was stratified by tumor stage, performance status (PS), start of frontline chemotherapy (< 4 mo vs more than 4 mo), gender, and prior taxane therapy. Univariate and multivariate Cox regression analyses were performed to evaluate the impact of baseline characteristics on overall survival (OS). Results: At randomization, 29% of pts had received prior taxane, 14% were PS2, 80% had stage IV disease, and 31% had started frontline therapy within the prior 4 months. Risk factors significantly affecting survival as determined by multivariate analysis are listed in the table . These factors were consistent when treatment was added to the model. Prior exposure to taxane was not predictive of survival; tumor stage was a significant univariate predictor (p=0.0349), but had relatively less impact in the multivariate model. Conclusion: These analyses identified several factors associated with reduced survival benefit from standard second line therapy. Consequently, alternative treatment strategies may be necessary in patients with poor prognosis. For example, more tolerable agents may enhance the benefit/toxicity ratio in these patients. [Table: see text] [Table: see text]

A non-comparative phase II study of bendamustine hydrochloride in patients with pretreated soft tissue sarcoma (German Sarcoma Group-AIO 001)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9525-9525
Author(s):  
F. Mayer ◽  
J. Schleicher ◽  
J. Huober ◽  
I. Meisinger ◽  
J. Pintoffl ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Ecog Performance Status ◽  
Adult Type ◽  
Efficacy Analysis ◽  
Clinically Significant

9525 Background: To assess the efficacy and safety of bendamustine hydrochloride, a nucleoside analogue with alkylating activity, in patients with adult type soft tissue sarcoma (STS) who have failed anthracyline-based chemotherapy. Methods: Pts with a ECOG performance status 0–2, measurable disease and adequate organ functions were eligible. All patients had inoperable locally advanced or metastatic disease and had progressive disease during or after first-line chemotherapy prior to study entry. Bendamustine was administered at a dose of 100 mg/sqm on day 1 and 2 every four weeks for a maximum of 6 cycles with tumour assessment every two cycles. The primary endpoint was overall response rate as defined by RECIST. The secondary endpoint was toxicity. A two-stage design was used (1st step: 14 pts, at least 1 PR in order to succeed with 2nd step; p0 = 5%, p1 = 25%, alpha = beta = 0.1). Results: 32 patients, median age 56 yrs (range, 18–74) with STS were recruited (3 pts not evaluable for efficacy analysis). In general the drug was well tolerated. Grade 3 toxicity was granulocytopenia in 9% and febrile neutropenia/fever in 3% of pts. No toxic death was seen in a total of 89 cycles administered. A single pt experienced a clinically significant allergic reaction (3%). Anti-tumour activity: 1 confirmed partial response (3%). A further 10 patients had progression arrest by cycle two (34%). Conclusions: The confirmed objective response rate is low. However, the incidence of progression arrest in pretreated adult type STS is in the range of other agents considered active in STS. The observed toxicity profile is favorable. Further investigation in STS appears warranted. No significant financial relationships to disclose.

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