AACR Planning Conflict-of-Interest Policy Following Incident at Annual Meeting
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 .
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 .
e11602^ Background: Fulvestrant downregulates breast tumor estrogen and progesterone receptor (ER and PgR) levels in a dose-dependent manner. Using an Automated Cellular Imaging System (ACIS), NEWEST reported that 4-wks’ treatment with fulvestrant high-dose (HD, 500mg/month+500mg on Day 14 of Month 1) significantly reduced ER levels in primary breast tumors v approved-dose (AD, 250mg/month). However, no significant difference was detected between the two doses on PgR levels. To allow comparison with previous studies, a non-automated H-score assessment was performed and compared with ACIS. Methods: ER and PgR H-scores were derived by manual assessment of % tumor cells in each of 5 staining categories (negative, very weak, weak, moderate, strong) in the same sections scored by ACIS. This microscopic assessment was performed by 2 experienced observers blind to ACIS and clinical data. Mean % changes in H-scores were then calculated (table). Results: Both scoring methods showed a greater effect for fulvestrant HD v AD on ER expression at Wk 4, but H-score provided better dose discrimination. ACIS showed no difference between fulvestrant HD v AD on PgR expression at Wk 4, however, a significantly greater reduction in PgR expression was detected with fulvestrant HD using H-score. Conclusions: The choice of scoring method for determining ER and PgR expression in pharmacodynamic studies such as NEWEST is critical. Compared with H-scores, ACIS has a narrower dynamic range and reduced ability to discriminate fulvestrant HD v AD, particularly on PgR expression. [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 .
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 .
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 .
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 .
3560^ Background: BAY 73–4506 is a potent inhibitor of the receptor tyrosine kinases (VEGFR, KIT, RET, FGFR and PDGFR) and serine/threonine kinases (RAF and p38MAPK). In in-vivo models, BAY 73–4506 has demonstrated a broad spectrum of antitumor activity. Methods: This phase I study investigated the safety and pharmacokinetic (PK)/pharmacodynamic (PD) profiles of BAY 73–4506, given orally in repeating cycles of 21 days on/7 days off, in patients with refractory CRC. PK assessments were performed on days 1 and 21 of cycle 1. PD markers - including DCE-MRI and plasma levels of VEGF/soluble VEGFR-2 - were assessed at each cycle. Tumor response was evaluated per RECIST. Results: 38 patients with actively progressing CRC were treated with BAY 73–4506 at doses of 60 mg (n = 1), 120 mg (n = 4), 160 mg (n = 26), and 220 mg (n = 7) once daily. Median treatment duration was 56.5 days (range, 7–219 days). Drug-related adverse events (AEs) of all grades reported in >20% of patients were hand-foot skin reaction (HFSR) (61%; CTC 3–4, 32%), fatigue (45%; CTC 3, 11%), hoarseness (24%; CTC 3, 3%), mucositis (24%), diarrhea (24%; CTC 3, 3%), anorexia (24%), and hypertension (21%; CTC 3, 13%). Treatment-related AEs leading to dose reduction, interruption, or discontinuation (in ≥2 of patients) were HFSR (26%), fatigue (18%), thrombopenia (8%), and hypertension (5%). BAY 73–4506 showed a dose-dependent increase in exposure up to 160 mg, at which point a plateau was reached. One of 27 evaluable patients achieved a partial response (4%), 15 had stable disease (SD) at least 7 weeks after the start of treatment (55%), and 6 had SD for more than 23 weeks (22%). Patients had extensive previous antitumor treatment, including bevacizumab (44%) and cetuximab (59%). Decreases in soluble VEGFR-2 levels and iAUC60s of Gd-DTPA by DCE-MRI demonstrated that BAY 73–4506 was active on biologically relevant markers. Conclusions: BAY 73–4506 dosing at 160 mg daily, using a treatment schedule of 21 days on/7 days off was feasible in patients with advanced refractory CRC. Promising clinical activity was shown, with a disease control rate (PR+SD) of 59% in evaluable patients. Mutational analysis of selected genes (KRAS, BRAF) is ongoing. [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 .
4105^ Background: This study evaluates induction bevacizumab and FOLFOX followed by concurrent chemoradiotherapy (CRT) with bevacizumab, weekly oxaliplatin, and continuous infusion 5-FU prior to surgical resection of newly-diagnosed Stage II or III rectal cancer. Methods: Eligible patients received one month of induction, biweekly bevacizumab (5mg/kg) and modified FOLFOX6. Patients then received 50.4Gy of radiation and concurrent bevacizumab (5 mg/kg on days 1, 15, and 29), oxaliplatin (50 mg/m2/week for 6 weeks), and 5-FU (200mg/m2/day) as a continuous IV infusion throughout radiation. Due to gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m2/week. Resection was performed 4 to 8 weeks after the completion of CRT. Adjuvant chemotherapy was started after 4 but less than 12 weeks following surgical resection and consisted of 6 biweekly treatments of modified FOLFOX6 and bevacizumab. Results: Twenty-six eligible patients were treated. The median age was 50. One patient developed a grade 4 arrhythmia during induction chemotherapy and was removed from the study. Of the remaining 25 patients, there were no other grade 3 or 4 toxicities during induction FOLFOX/bevacizumab. Toxicity was more significant during chemoradiation. Any grade 3 toxicity was experienced by 19 of 25 (76%) patients. Grade 3 toxicities included diarrhea (40%), neutropenia (16%), pain (16%), fatigue (8%), nausea (8%), and radiation dermatitis (8%) and bleeding with menstruation (4%). Grade 4 toxicities included neutropenia (4%), sepsis (4%) and nausea/diarrhea (4%). Six of 25 resected patients (24%) had a complete pathologic response. Eight of 25 patients (32%) developed post-operative wound complications including infection/abscess (n=4), fistula (n=2), ischemic colonic reservoir (n=1) and sterile fluid collection (n=1). Nine of 25 (36%) patients developed postoperative wound complications including infection (n=4), delayed healing (n=3), leak/abscess (n=2), sterile fluid collection (n=2), ischemic colonic reservoir (n=1), and fistula (n=1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen to similar to other fluorouracil based chemoradiaton regimens. The high incidence of post-operative wound complications is concerning and consistent with other reports utilizing bevacizumab prior to major surgical resections. [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 .
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 .
4067^ Background: Pmab, a fully human antibody to the epidermal growth factor receptor (EGFR), is indicated as monotherapy for treatment of metastatic colorectal cancer (mCRC). Mutation status of KRAS in mCRC tumors has recently been shown to predict response to anti-EGFR antibody therapies. The effect of KRAS tumor status on the efficacy of second-line pmab + FOLFIRI was evaluated in this prospective analysis. Methods: Patients (pts) were enrolled in this phase 2, open-label, single-arm study after failure of first-line treatment with oxaliplatin-based chemotherapy + bevacizumab. Pts with unresectable, measurable disease; ECOG status 0/1; with tumor samples available for KRAS testing were eligible. Pts received pmab 6 mg/kg + FOLFIRI Q2W until disease progression or intolerability. Tumor assessments were performed at wks 8, 16, 24, 32, and Q12W thereafter. DNA extracted from fixed tumor sections was used to determine KRAS status by real-time PCR. Efficacy (objective response, progression-free survival [PFS], and overall survival [OS]) and safety were evaluated by KRAS status. Results: In an interim analysis (May 2008) of 115 pts who had received ≥ 1 dose of pmab, 109 pts had known KRAS status (59% had tumors with wild-type [WT] KRAS, 41% had mutant [MT] KRAS tumors), and 102 pts had the opportunity to have their first tumor assessment. Efficacy outcomes by KRAS status are shown ( Table ). Pmab-related AEs were reported in 93% of pts; 87 pts (76%) had ≥ grade 3 AEs (related and unrelated). Most common AEs were skin-related toxicities (86% of pts), diarrhea (72%), and nausea (53%); there was no evidence that incidence of AEs was related to KRAS status. Conclusions: In interim analyses, numerical differences in PFS and OS in favor of pts with WT KRAS were observed. Pmab had a safety profile consistent with other FOLFIRI + pmab trials. Final efficacy and safety data will be presented. [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 .
