Effect of macroscopic vascular invasion (MVI), extrahepatic spread (EHS), and ECOG performance status (ECOG PS) on outcome in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib: Analysis of two phase III, randomized, double-blind trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4580-4580 ◽  
Author(s):  
J. Bruix ◽  
A. Cheng ◽  
Y. Kang ◽  
C. Tsao ◽  
S. Qin ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Interest Policy ◽  
Grade 3 ◽  
Ecog Ps

4580^ Background: The landmark phase III SHARP trial (Llovet et al, N Engl J Med, 2008) showed that sorafenib is effective and safe for the treatment of advanced HCC. These results were confirmed in an Asian population in the phase III Asia-Pacific (AP) study (Cheng et al, Lancet Oncol, 2009). We compared outcomes of sorafenib treatment in patients enrolled in the SHARP and AP trials with known baseline predictors of poor prognosis. Methods: Patients with advanced, unresectable, measurable HCC, ECOG PS 0–2, Child-Pugh A, and no prior systemic therapy for HCC were randomized to sorafenib 400 mg BID or placebo (SHARP: N=602; AP: N=226). Patients in the AP study had more evolved disease and a predominance of hepatitis B infection. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 days from first demonstration of response), and safety. Results: Efficacy results are shown in the table . The incidence of grade 3/4 drug-related adverse events (AEs) across subgroups in each study was consistent with the overall population for each study. The most common grade 3/4 AEs in all sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib is effective and safe for the treatment of advanced HCC in patients globally, irrespective of baseline ECOG PS and presence or absence of MVI and/or EHS. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma (HCC): Asia-Pacific (AP) trial subgroup analyses by baseline transaminase (ALT/AST)/α-fetoprotein (AFP) levels

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4590-4590 ◽  
Author(s):  
S. Qin ◽  
T. Yang ◽  
W. Tak ◽  
S. Yu ◽  
C. Tsao ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Hepatic Function ◽  
Principal Investigator ◽  
Phase Iii ◽  
Asia Pacific ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Interest Policy

4590^ Background: Results of the phase III, randomized, double blind, placebo-controlled AP trial demonstrated that sorafenib is effective and safe for the treatment of advanced HCC in patients from the AP region (Cheng et al, Lancet Oncol, 2009). Hepatic function influences treatment as a measure of organ damage and tumor stage. We performed subset analyses of the AP study dataset according to baseline hepatic function, as indicated by levels of ALT/AST and AFP. Methods: Patients (N=226) with advanced HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy were randomized 2:1 to receive sorafenib 400 mg BID or placebo. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 days from first demonstration of response), time to progression (TTP) and safety. Patients were grouped by baseline levels of ALT/AST (normal, mild, or moderate) and AFP (normal or abnormal). Results: Median TTP, OS and DCR by subset are shown in the table . The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib was effective and safe in patients from the AP region with advanced HCC within a broad range of baseline hepatic enzyme and AFP levels. These results suggest that sorafenib is an effective treatment for HCC, irrespective of baseline ALT/AST or AFP levels. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Randomized, double blind, multicenter, phase II study of pemetrexed (PEM), carboplatin (CARBO), bevacizumab (BEV) with enzastaurin (ENZ) or placebo (PBO) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer (NSCLC): Hoosier Oncology Group (HOG) LUN06–116

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8035-8035
Author(s):  
E. M. Casey ◽  
W. Harb ◽  
D. Bradford ◽  
J. Bufill ◽  
S. Nattam ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Stage Iiib ◽  
Disease Stage ◽  
Therapeutic Area ◽  
Interest Policy ◽  
Grade 3 ◽  
Ecog Ps

8035^ Background: Pre-clinical data suggests that ENZ and BEV may have complementary effects in inhibiting angiogenesis. This study compared ENZ vs PBO in combination with PEM+CARBO+ BEV. Methods: Pts ≥18 years of age, non-squamous NSCLC, no prior systemic therapy, disease measurable by RECIST, and ECOG PS 0–1 were randomized. Pts received either PBO or 500 mg ENZ daily after loading dose of 375 mg orally, TID, on day 1, cycle 1. Starting on day 8, cycle 1, patients received PEM 500mg/m2, CARBO AUC 6 and BEV 15mg/kg, intravenously, every 21 days. After 4 cycles, pts continued on BEV+ENZ or BEV+PBO. Pts were stratified by ECOG status, disease stage and site with a planned sample size of 90 pts. Primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR) and toxicity. Results: Study was terminated after a planned interim analysis for safety and efficacy. From October 2007 to July 2008, 40 pts were enrolled: 20 in each arm. Median age was 60.5 years (range: 44 to 78); M 52.5%, F 47.5%; ECOG PS 0/1 52.5% and 47.5%; stage IIIB/IV 15% and 85%. Baseline characteristics were well matched. The PEM+CARBO+BEV+ENZ arm received a median of 3 cycles of therapy and the PEM+CARBO+BEV+PBO arm 4 cycles. Median PFS was 4.3 mo and 4.2 mo for ENZ and PBO, respectively (unadjusted HR: 0.94, 95% CI [0.39, 2.33]). ORR for ENZ and PBO was 20% and 25%, respectively. Overall, grade 3/4 toxicities were similar in both arms. One patient in ENZ arm experienced a grade 3/4 hemorrhage (vs. none in the PBO arm). Two patients experienced a GI perforation (1 on each arm): 1 resulted in death on the PBO arm. Both patients had a history of diverticulosis. Conclusions: Based upon the results of this interim efficacy analysis, addition of ENZ to PEM+CARBO+BEV will not significantly prolong PFS in patients with stage IIIB/IV NSCLC. This combination does not warrant further study in NSCLC. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Biomarker analyses from a phase III, randomized, open-label, first-line study of gefitinib (G) versus carboplatin/paclitaxel (C/P) in clinically selected patients (pts) with advanced non-small cell lung cancer (NSCLC) in Asia (IPASS)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8006-8006 ◽  
Author(s):  
M. Fukuoka ◽  
Y. Wu ◽  
S. Thongprasert ◽  
C. Yang ◽  
D. Chu ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Phase Iii ◽  
Gene Copy ◽  
Therapeutic Area ◽  
First Line ◽  
Interest Policy ◽  
Financial Relationships

8006^ Background: IPASS demonstrated overall superiority of first-line G vs C/P for progression-free survival (PFS) in never/light ex-smokers with stage IIIB/IV adenocarcinoma NSCLC in Asia. PFS favored CP initially and then G. Outcome was correlated with biomarkers (preplanned exploratory objective). Methods: 683 patients provided tissue samples. Analyses included primary endpoint PFS (Cox proportional hazards) and secondary endpoint objective response rate (ORR; logistic regression) by biomarker status. Results: EGFR mutation (M) status was evaluable in 437 pts by Amplification Refractory Mutation System (ARMS; 60% M+). M+ pts had significantly longer PFS and higher ORR and M- pts significantly shorter PFS and lower ORR with G than C/P. In M unknown pts PFS and ORR were similar to overall population. Post hoc analysis of overall survival favored G in M+ pts (31% maturity; HR 0.78; 95% CI 0.50–1.20) and C/P in M- pts (53% maturity; HR 1.38; 95% CI 0.92–2.90); differences were not statistically significant and follow-up is ongoing. EGFR gene-copy number was evaluable in 406 pts by fluorescence in situ hybridization (FISH; 61% FISH +). Similar PFS and ORR results to analyses by M status were observed, driven by the overlap in EGFR FISH and M status. EGFR protein expression (PE) was evaluable in 365 pts by immunohistochemistry (73% PE+). PFS outcomes did not differ statistically between PE+ and PE-. ORR favored G in both PE+ and - pts. Conclusions: EGFR M status was a strong predictive biomarker for the efficacy of G vs C/P in this clinically selected first-line setting. [Table: see text] No significant financial relationships to disclose. ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5021-5021 ◽  
Author(s):  
C. N. Sternberg ◽  
C. Szczylik ◽  
E. Lee ◽  
P. V. Salman ◽  
J. Mardiak ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Median Duration ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Continuous Treatment ◽  
Phase Iii ◽  
Therapeutic Area ◽  
Interest Policy ◽  
Treatment Naïve

5021^ Background: Pazopanib, an oral multikinase angiogenesis inhibitor, has shown clinical efficacy in patients (pts) with advanced RCC. In this study (VEG105192), the efficacy and safety of pazopanib was compared with placebo in advanced RCC. Methods: Pts (N = 400 planned) with clear cell advanced RCC and measurable disease with no prior treatment or 1 prior cytokine-based treatment, were stratified and randomized (2:1) to pazopanib 800 mg QD or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate (RR), and safety. The study had ≥ 90% power to detect an 80% improvement in PFS and a 50% improvement in OS, by stratified log-rank tests with α = 0.025 one-sided. Pts received continuous treatment until disease progression (PD), death or unacceptable toxicity. Upon PD, placebo pts could receive pazopanib via an extension study. Final PFS, RR and safety results are reported here. Results: A total of 233 treatment-naïve and 202 cytokine-pretreated pts were enrolled (290 pazopanib; 145 placebo). Pt characteristics were balanced between the 2 arms. ECOG 0/1 was 42%/58% and 41%/59% for pazopanib and placebo pts, respectively. PFS was significantly prolonged with pazopanib in the overall study population (9.2 vs 4.2 mos; HR: 0.46; 95% CI: 0.34, 0.62; p < 0.0000001), in treatment naïve pts (11.1 vs 2.8 mos; HR: 0.40; 95% CI: 0.27, 0.60; p < 0.0000001), and in cytokine-pretreated pts (7.4 vs 4.2 mos; HR: 0.54; 95% CI: 0.35, 0.84; p < 0.001). RR was 30% with pazopanib (vs 3% with placebo) and median duration of response was 58.7 wks. Median duration of exposure was 7.4 mos (pazopanib) and 3.8 mos (placebo). The majority of adverse events (AEs) were grade 1 or 2. Most common AEs in pazopanib-treated pts were diarrhea (52%; 4% Gr 3/4), hypertension (40%; 4% Gr 3/4), hair color change (38%; <1% Gr 3/4), nausea (26%; <1% Gr 3/4), anorexia (22%; 2% Gr 3/4), and vomiting (21%; 2% Gr 3/4). The most common laboratory abnormality was ALT elevation (53%; 10% Gr 3; 2% Gr 4). Conclusions: Pazopanib monotherapy was well tolerated and demonstrated a significant improvement in PFS and RR compared to placebo. Final OS results are awaited. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Randomized, open-label, multicenter phase II study of bevacizumab in combination with carboplatin and paclitaxel in chemotherapy-naive Japanese patients with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC): JO19907

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8036-8036 ◽  
Author(s):  
M. Nishio ◽  
T. Horai ◽  
H. Kunitoh ◽  
Y. Ichinose ◽  
Y. Nishiwaki ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Phase Ii ◽  
Conflict Of Interest ◽  
Phase Ii Study ◽  
Principal Investigator ◽  
Phase Iii ◽  
Therapeutic Area ◽  
Open Label ◽  
Interest Policy

8036^ Background: Two phase III trials (ECOG 4599 and BO17704) demonstrated that the addition of bevacizumab (Bev) to platinum-based regimens improved overall and/or progression-free survival (PFS) in patients (pts) with advanced non-squamous NSCLC (Sandler et al. NEJM 2006; Manegold et al. ESMO2008). However, no investigation with Bev has been conducted in Japanese NSCLC pts. Methods: This randomized, open-label phase II study compared a 3-weekly regimen of 15mg/kg of Bev plus carboplatin/paclitaxel (CP) versus CP alone. The primary endpoint was PFS; secondary endpoints included overall survival (OS), response rate (RR) and safety. Eligibility criteria: histologically or cytologically documented previously untreated advanced or recurrent non-squamous NSCLC; ECOG PS 0–1; no brain metastases. A size of 180 pts was planned to be randomized to: C AUC=6 and P 200mg/m2 q3 wks for up to 6 cycles plus Bev continued to progression at 15mg/kg q3 wks, or CP alone at the randomization ratio of 2:1. The study was designed to observe a 20% reduction in the risk of a PFS event in the Bev arm compared with control. Results: Between 4/07 and 3/08, 180 pts were accrued. Three pts of them were ineligible and 3 pts were not dosed at all. PFS (as assessed by investigators) and RR were significantly improved. OS is immature due to short duration of follow up. Updated PFS results as assessed by the central review committee and OS data will be provided. No new safety signals for Bev were detected. Conclusions: This is the first study of Bev in Japanese pts with NSCLC. The addition of 15mg/kg of Bev to CP significantly improved PFS and RR. The HR of PFS seemed at least as good as previous trials outside Japan. Safety of Bev was within a range already reported. This study confirms the efficacy and safety of Bev in Japanese pts with NSCLC. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Geparquinto: An interim safety analysis of epirubicin/cyclophosphamide followed by docetaxel with or without bevacizumab as neoadjuvant chemotherapy for primary breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11519-e11519
Author(s):  
G. Von Minckwitz ◽  
I. Bauerfeind ◽  
B. Gerber ◽  
H. Eidtmann ◽  
M. Kaufmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Main Phase ◽  
Therapeutic Area ◽  
Oncology Research ◽  
Interest Policy ◽  
Grade 3

e11519^ Background: The GeparQuinto trial is investigating the incorporation of bevacizumab (B), RAD001 (everolimus) for HER2-negative, and lapatinib for HER2-positive patients (pts) into neoadjuvant treatment regimens. As these targeted agents have not yet been adequately tested in combination with epirubicin (E), cyclophosphamide (C), and docetaxel (T) chemotherapy, a run-in phase of the trial was conducted for safety reasons. Methods: Starting in 11/2007, 62 pts received 4 cycles of E: 90 mg/m2 and C: 600 mg/m2, both on day 1 q day 21 followed by 4 cycles of T: 100 mg/m2, day 1 q day 21. Pts were randomized to receive this chemotherapy alone (EC-T, n=32) or concomitantly with B: 15 mg/kg i.v., day 1 q day 21 (ECB-TB, n=30). Main eligibility criteria for this part of the study were: histologically confirmed, HER2-negative, locally advanced breast cancer (cT3 cN+ and cT4), female, and ≥18 years of age with normal cardiac function (LVEF >55%). This interim toxicity analysis was a prerequisite for opening the main phase of the HER2-negative trial part to also include pts with cT2 tumors. Results: 61 pts received all cycles of EC (n=31 EC-T, n=30 ECB-TB), 1 pt discontinued on investigator's decision, 1 pt discontinued after EC due to disease progression. 18 pts received all cycles of T in each of the EC-T and ECB-TB groups. Reasons for discontinuation of T were adverse events (n=2 EC-T, n=1 ECB-TB) or investigator's decision (n=1 EC-T). 17 pts completed all cycles of B. Statistically significant differences in toxicities were only observed for grade 3–4 leucopenia during EC (40.6%) and ECB (70.0%; p=0.024) and for grade 1–4 [grade 3–4] mucositis during T (52.4% [9.5%]) and TB (100% [36.8%]; p<0.001 [p=0.060]). No statistically significantly different levels of other hematological or non-hematological toxicities were reported between the two arms. Conclusions: Addition of B to EC followed by T is feasible with the only increase in toxicity due to leucopenia and mucositis. Based on these data, the main phase of the trial was opened and has included over 450 pts to date. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

An analysis of safety in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) receiving chemotherapy (CT) with or without panitumumab (pmab) in a phase III clinical trial (SPECTRUM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6050-6050 ◽  
Author(s):  
J. B. Vermorken ◽  
J. Stöhlmacher ◽  
I. Davidenko ◽  
E. Winquist ◽  
L. Licitra ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clin Oncol ◽  
Disease Progression ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Phase Iii ◽  
Therapeutic Area ◽  
Oncology Research ◽  
Interest Policy

6050^ Background: The epidermal growth factor receptor (EGFR) is an important target for treatment of patients with SCCHN. Pmab is a fully human monoclonal antibody against EGFR. This study is planned to assess the safety and efficacy of pmab in combination with a standard platinum-based CT regimen for patients with R/M disease. Methods: This ongoing, global, phase III, open-label, randomized (1:1) study is enrolling pts with R/M SCCHN. Pts receive cisplatin 100 mg/m2 IV on day 1 plus 5-FU (1,000 mg/m2) continuous IV daily on days 1–4 ± pmab (9 mg/kg on day 1) every 21 days for up to 6 cycles. Changes to carboplatin (AUC 5) are allowed for specific cisplatin-related toxicities. Pts in the pmab arm without disease progression after 6 cycles may remain on pmab monotherapy until disease progression or intolerability. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, response rate, duration of response, and safety. This study includes multiple planned safety interim analyses conducted by an independent Data Monitoring Committee (DMC). The latest analysis included the first 300 of approximately 650 planned patients. Results: Of 300 pts enrolled, 88% are male; median age is 59 years (range 31–82); ECOG PS 0: 32%, PS 1: 68%. Of the 300 patients, 99% received any study treatment and 76% had ended all CT. Median follow-up time is 13.9 weeks. The rate of any grade 5 treatment-related AE was 3.4%. Adverse events of interest are shown in the Table. Conclusions: After the interim safety analysis of the first 300 pts conducted by the independent DMC, SPECTRUM continues per protocol. Enrollment is estimated to be completed in Feb 2009. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Impact of prior surgical resection with curative intent on the efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma (HCC): Subset analysis of the Asia-Pacific (AP) study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15518-e15518 ◽  
Author(s):  
T. Yang ◽  
S. Qin ◽  
W. Tak ◽  
S. Yu ◽  
C. Tsao ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Surgical Resection ◽  
Partial Hepatectomy ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
Efficacy And Safety ◽  
Curative Intent ◽  
Advanced Hcc ◽  
Interest Policy

e15518^ Background: The multinational, phase III, randomized, double-blind, placebo-controlled AP study demonstrated that sorafenib is effective and safe for the treatment of advanced HCC in patients from the AP region (Cheng, et al. Lancet Oncol, 2009). Surgical resection with curative intent is a commonly used procedure for the treatment of HCC; however, tumor recurrence occurs in the majority of patients. Hence, it is of interest to analyze the efficacy and safety of sorafenib in patients who had undergone prior partial hepatectomy. Methods: Patients (N=226) with advanced HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy were randomized 2:1 to receive either sorafenib 400 mg BID or placebo. End points included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 d from first demonstration of response), time-to-progression (TTP), and safety. Results: Of 226 patients enrolled, 70 had previously undergone partial hepatectomy. Median TTP, OS, and DCR by subset are shown in the table. The safety profile of sorafenib in patients with and without prior hepatectomy was similar to that reported for the total study population. The most common grade 3/4 adverse events in the sorafenib groups were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib was safe for the treatment of advanced HCC in patients from the AP region, whether or not they had undergone prior surgical resection. Sorafenib treatment resulted in similar TTP in patients with and without a history of prior partial hepatectomy, and the magnitude of TTP was similar in both groups to that in the overall population. Due to small sample size, further study is warranted. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Phase III, randomized, open-label, first-line study of gefitinib (G) versus carboplatin/paclitaxel (C/P) in selected patients (pts) with advanced non-small cell lung cancer (NSCLC) (IPASS): Evaluation of recruits in Japan

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8044-8044 ◽  
Author(s):  
Y. Ohe ◽  
Y. Ichinose ◽  
Y. Nishiwaki ◽  
N. Yamamoto ◽  
S. Negoro ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Advanced Nsclc ◽  
Principal Investigator ◽  
Phase Iii ◽  
Symptom Improvement ◽  
Tolerability Profile ◽  
Interest Policy ◽  
Interaction Test

8044^ Background: The IRESSA Pan Asia Study (IPASS) demonstrated superiority of G vs C/P in 1,217 clinically selected chemonaïve pts in Asia with advanced NSCLC. PFS favored C/P initially then G, likely driven by different outcomes according to EGFR mutation (M) status. We report the planned analyses of 233 recruits in Japan (19% of overall population). Methods: From Mar 06 to Oct 07, chemonaïve, never/light ex-smokers with stage IIIB/IV NSCLC and adenocarcinoma histology were randomized to G 250 mg/day (n=114) or C (AUC 5 or 6)/P (200 mg/m2) (n=119). Primary objective was PFS in ITT population; a treatment by country interaction test (Japan vs other) was performed. Secondary endpoints were overall survival (OS), objective response rate (ORR, RECIST), QoL (FACT-L, TOI), symptom improvement (LCS subscale of FACT-L), and tolerability. Results: PFS results in pts in Japan did not significantly differ from other pts (interaction test p=0.4736). G demonstrated superior PFS compared with C/P (HR 0.69; 95% CI 0.51–0.94; p=0.0191); effect was not constant over time, favoring C/P initially then G. Preliminary OS (25% maturity; follow-up ongoing) was similar for G and C/P (HR 0.89; 95% CI 0.53–1.48). ORR for G was 41% vs 35% for C/P;odds ratio [OR] 1.34; 95% CI 0.78–2.30; p=0.2967. QoL improvement rate (TOI) was 43% for G and 28% for C/P (OR 1.92; 95% CI 1.11–3.34; p=0.0200); QoL (FACT-L 41 vs 43%; OR 0.94; 95% CI 0.56–1.60; p=0.8263) and symptom (LCS 42 vs 46%; OR 0.85; 95% CI 0.50–1.43; p=0.5340) improvement rates were similar for G and C/P. Tolerability profile was more favorable with G than C/P. There were no deaths due to ILD-type events (frequency 1.8% [G] vs 0% [C/P]). Conclusions: Efficacy and safety data for pts in Japan were generally consistent with overall population. G demonstrated improved PFS and ORR, similar OS, higher QoL (TOI) and similar symptom improvement rates, and a more favorable tolerability profile compared with C/P in chemonaïve, never/light ex-smokers with advanced NSCLC and adenocarcinoma histology. In IPASS, EGFR M status appeared to be a strong predictive biomarker for G efficacy compared with C/P. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Chemosensitivity (CS) of patient (pt) breast cancer (BrCa) cells in vitro: Correlation with prior chemotherapy (CT) and implications for personalized treatment planning

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11563-e11563
Author(s):  
P. W. Whitworth ◽  
C. A. Presant ◽  
J. Rutledge ◽  
A. Hallquist ◽  
M. Perree ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Annual Meeting ◽  
Conflict Of Interest ◽  
Principal Investigator ◽  
International Standards ◽  
New Drugs ◽  
Therapeutic Area ◽  
Oncology Research ◽  
Interest Policy

e11563^ Background: A predictive BrCa chemosensitivity assay will facilitate individualized treatment. Unlike older assays, the Microculture Kinetic (MiCK) assay measures active apoptosis. In order to determine the in vitro CS of pt BrCa cells, we tested pt tumor cells (tc) in vitro using the MiCK assay. Methods: Tumor excisions or biopsies were sent to a central laboratory, prepared using our previously described MiCK technology (Lab Invest 74: 557, 1996) and tc apoptosis was measured over 48 hours with various drugs. In vitro results were compared to clinical status. CS was measured in kinetic units of apoptosis (KU) with inactive <1.0, low CS 1.0–2.59, moderate CS 2.6–4.2, and high CS >4.2. Physicians (MDs) decided on CT without knowledge of MiCK results. Results: 57 pts were evaluable for MiCK results. CS to drugs for tc from pts with no prior CT was: paclitaxel (P) mean 1.2 KU, cyclophosphamide as 4-hydroxycyclophosphamide (4HC) 2.7, doxorubicin (Dox) 1.8, epirubicin (Epi) 2.1, docetaxel (Doc) 2.0, vinorelbine 0.9, gemcitabine (Gem) 0.7, liposomal D 1.4, carboplatin (Carbo) 1.7, cisplatin (Cis) 2.0, and topotecan 1.2. Combinations tested in some pts showed Carbo-P 2.6 KU and Cis-Gem 2.7. These results were compared to CS of tc from pts with prior CT. CS for pts with prior CT were P 1.8 KU, Doc 1.7, Dox 1.9, Epi 2.9, 4HC 1.1, and Vin 1.2. Although there was no difference between the CS of BrCa cells with or without prior CT for Dox or Epi, CS for 4HC was statistically significantly reduced after prior CT (p<0.0003). Overall, Doc had higher CS than P (p<0.004), Epi higher than Dox (p<0.0001), and 4HC higher than P (p<0.0001) or Carbo (p=0.03). However, in individual pts, P was higher or equal to Doc in 5/18 (28%), Dox higher or equal to Epi in 9/36 (25%), and P higher or equal to 4HC in 5/32 (16%). Conclusions: This indicates that the MiCK assay may be used to evaluate CS of BrCa cells from individual pts. After prior CT, BrCa cells show altered CS profiles, with persistent CS to Dox or Epi but reduced CS to 4HC. These data may be useful to MDs in selecting CT for individual pts. MiCK may also be useful in developing new drugs and new combination therapies. ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Sign in / Sign up

Export Citation Format

Share Document