BOA会议中的报告均是精选出ASCO年会中肺癌、乳腺癌、结直肠癌、妇科肿瘤、淋巴瘤、泌尿系肿瘤等方面的精彩论文进行报告。根据会议日程中的报告题目找出了各报告的摘要，以下为胃肠肿瘤专场的报告摘要。
摘要号：LBA3501
题目：Results of the X-PECT study: A phase III randomized double-blind placebo-controlled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC).
X-PECT研究结果：比较perifosine联合卡培他滨(P-CAP)和安慰剂联合卡培他滨(CAP)治疗难治性转移性结直肠癌(mCRC)患者的随机、双盲、安慰剂对照III期研究
摘要：
Background: Perifosine (P) is an oral, synthetic alkylphospholipid that inhibits or modifies signal transduction pathways including AKT, NFkB and JNK. A randomized phase II study examined P-CAP vs. CAP in pts with 2nd or 3rd line mCRC. This study showed improvement in mTTP (HR 0.254 [0.117, 0.555]) and mOS (HR 0.370 [0.180,0.763]). Based on these results, a randomized phase III study of P-CAP vs. CAP with a primary endpoint of overall survival (OS) in pts with refractory mCRC was initiated.
Methods: The study was a prospective, randomized, double-blind, placebo-controlled randomized phase III trial. Eligible pts had mCRC which was refractory to all standard therapies. Pts randomized 1:1 to Arm A = P-CAP (P 50 mg PO QD + CAP 1000 mg/m2PO BID d1-14) or Arm B = CAP (placebo + CAP 1000 mg/m2 PO BID d 1-14). Cycles were 21 days. Baseline tumor block collection and a biomarker cohort of pts with pre- and on-treatment tumor and blood samples were performed.
Results: Between 3/31/10 and 8/12/11, 468 pts were randomized, 234 pts were in each arm. Baseline demographics were balanced between the arms: age < 65y (A: 65%, B: 58.5%), male (A: 57.7%, B: 53.0%), ECOG PS 0 (A: 39.7%, B: 39.7%), K-ras mutant (A: 50.4%, B: 51.3%), and median number of prior therapies (A: 4, B: 4). As of 3/19/12, median follow up was 6.6 months. Median overall survival: Arm A = 6.4 mo, Arm B = 6.8 mo, HR 1.111 [0.905,1.365], p = 0.315. Median overall survival for K-ras WT pts: Arm A = 6.6 mo, Arm B = 6.8 mo, HR 1.020 [0.763,1.365], p = 0.894; K-ras mutant pts: Arm A = 5.4 mo, Arm B = 6.9 mo HR 1.192 [0.890,1.596], p = 0.238.
Conclusions: Despite promising randomized phase II data, this phase III study shows no benefit in overall survival adding perifosine to capecitabine in the refractory colorectal cancer setting. Response rate, progression free survival, and safety data will be presented. Biomarker analysis is pending to see if subgroups of patients may have potential benefit.
摘要号：LBA 3500
题目：Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy and safety results of the International GERCOR DREAM phase III trial.
一线化疗加贝伐单抗治疗后贝伐单抗加或不加厄洛替尼作为转移性结直肠癌的维持治疗： GERCOR DREAM国际III期研究的疗效和安全性结果
摘要
Background: Therapy targeting VEGF or EGFR demonstrated clinical activity in combination with chemotherapy (CT) in mCRC but monoclonal antibodies cannot be associated. The DREAM trial compares a maintenance therapy (MT) with bev +/- EGFR tyrosine kinase inhibitor erlotinib (E) after a first-line Bev-based induction therapy (IT) in pts with mCRC.
Methods: Pts with previously untreated and unresectable mCRC were eligible. After a Bev-based IT with FOLFOX or XELOX or FOLFIRI, pts without disease progression were randomized to MT between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev+E (B 7.5 mg/kg q3w, E 150 mg/day continuously; arm B). Pts were treated until progression or unacceptable toxicity. The primary endpoint was PFS on MT.
Results: The study enrolled 700 pts from 01/2007 to 11/2011 in 3 countries (France, Canada, Austria). 446 (63.7%) pts were randomized for MT (arm A, N=224; arm B, N=222). Among the 446 randomized pts, IT regimen was FOLFOX-Bev in 265 pts (59.4%), XELOX-Bev in 135 pts (30.3%), and FOLFIRI-Bev in 46 pts (10.3%). Baseline characteristics of randomized pts were (arm A/B): ECOG PS 0, 60% in both arms; normal LDH level 47%/49%; normal alkaline phosphatase level 48%/50%; synchronous metastasis 83%/82%. The median no of MT cycles was 6 in both arms. With a median follow-up of 31.0 months, 327 PFS events were observed. Median MT-PFS were 4.6 m in arm A vs 5.8 m in arm B (HR 0.73 [95%CI: 0.59-0.91], P=.005). Median PFS from inclusion were 9.2 m vs 10.2 m. During MT, in arm A vs arm B, grade 3-4 diarrhea (<1% vs 9%) and grade 3 skin toxicity (0% vs 19%) were the main differences in toxicity. Severe adverse events from randomization related to B or E were 6 in arm A and 7 in arm B. Overall survival is not mature.
Conclusions: The addition of erlotinib to bevacizumab after induction therapy significantly improves the duration of maintenance PFS, following induction with first-line chemotherapy plus bevacizumab, in patients with unresectable metastatic colorectal cancer.
摘要号：3513
题目：The prognostic importance of miRNA-21 in stage II colon cancer: A population-based study.
miRNA-21在II期结肠癌中的预后价值：一项人群研究
摘要：
Background: Adjuvant chemotherapy for stage II colon cancer patients is still controversial and the debate on which patients should be considered as high risk patients is still ongoing. The decision is based on clinical and pathological markers of risk, which are inadequately informative in most of the patients, and better methods are highly needed. The aim of the present study was to investigate the possible prognostic importance of miRNA-21, quantified by in situ hybridization (ISH), in a unique, large population-based cohort of patients treated for stage II colon cancer patients.
Methods: The study included all patients diagnosed with stage II colon cancer in Denmark in the year 2003 (711 patients), representing a full population of five million people. Patients receiving adjuvant chemotherapy were excluded (N=15). One paraffin-embedded tissue block was obtained from each patient. A 6μm-thick section was processed for formazan-based chromogenic miR-21 ISH analysis and counter stained with nuclear red. The blue miR-21 ISH signal was assessed by image analysis to obtain two quantitative expression estimates: the total blue area (TB) and the ratio of TB with the nuclear density (TBR).
Results: The miRNA-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. Patients expressing high levels of miRNA-21 (high mean TBR) had significantly inferior cancer specific survival (CSS): HR = 1.26 (95% CI; 1.15-1.60), p <0.001. In the COX regression analysis (including; gender, T-category, malignancy grade, localization, tumor perforation, tumor fixation, number of lymph nodes and MSI status), mean TBR was found to be an independent predictive marker of poor CSS, HR = 1.41 (95%CI; 1.19-1.67, p< 0.001). The same applied to TB.
Conclusions: The present study shows that increasing miRNA-21 expression level is significantly correlated to decreasing CSS. Analyses of miRNA-21 should be considered as a potential adjunct in the selection of high risk stage II patients.
摘要号：CRA3503
题目：Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: Results of a randomized phase III intergroup study (TML study).
贝伐单抗(BEV)联合化疗(CT)治疗后首次进展的转移性结直肠(mCRC)患者继续给予贝伐单抗和化疗：随机III期组间研究（TML研究）
摘要：
Background: BEV in combination with fluoropyrimidine-based CT is standard treatment for mCRC in the first-line (1L) and BEV-naïve second-line (2L) settings. This is the first randomized study evaluating the benefit of continuing BEV in combination with standard CT as 2L treatment for patients with mCRC who progressed after receiving a standard BEV-containing regimen in the 1L setting.
Methods: Patients with unresectable, histologically confirmed mCRC who progressed within 3 months after discontinuation of 1L BEV + CT were randomised to 2L fluoropyrimidine-based CT ± BEV (2.5 mg/kg/wk equivalent). Choice of oxaliplatin- or irinotecan-based 2L CT was dependent on the regimen used in 1L (crossover) and included as a stratification variable. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate and safety.
Results: 820 patients were randomized from February 2006 to June 2010 (409 to BEV + CT and 411 to CT alone). Baseline patient and disease characteristics were well balanced between arms. The study met its primary endpoint; median OS was 11.2 months for BEV + CT and 9.8 months for CT (HR=0.81; 95% CI 0.69–0.94; unstratified log-rank test, p=0.0062). Median PFS was 5.7 months for BEV + CT and 4.1 months for CT (HR=0.68; 95% CI 0.59–0.78; unstratified log-rank test, p<0.0001). The response rate was 5.4% for BEV + CT and 3.9% for CT (unstratified Chi-Square Test, p=0.3113). The adverse event profile was consistent with previously reported data for BEV + CT. Compared with historical data from BEV treatment in 1L or 2L mCRC, BEV-related adverse events were not increased when continuing BEV beyond progression.
Conclusions: This is the first randomized study to prospectively investigate the impact of continuing BEV treatment in 2L mCRC for patients who progressed after receiving a BEV-containing regimen in 1L. Our findings demonstrate that BEV + CT (crossed over from 1L regimen) continued beyond progression significantly prolongs OS and PFS in 2L mCRC. Additional analysis (including biomarker evaluation) is ongoing.
摘要号：3505
题目：Effects of prior bevacizumab (B) use on outcomes from the VELOUR study: A phase III study of aflibercept (Afl) and FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin regimen.
VELOUR研究中贝伐单抗(B)的预使用对结果的影响：一项在含奥沙利铂方案治疗失败后的转移性结肠癌(mCRC)患者中给予aflibercept(Afl)联合FOLFIRI的III期研究
摘要：
Background: Aflibercept (Afl; also known as VEGF Trap) is a recombinant human fusion protein that acts as a decoy receptor and prevents the interaction of vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF) with their receptors. In the phase III VELOUR study, Afl + FOLFIRI improved overall survival (OS) compared with FOLFIRI + placebo (pbo) in mCRC (ECCO 2011, abstract 6LBA). We report outcomes from a pre-specified subgroup analysis by prior B use.
Methods: Pts with mCRC and progression during or after oxaliplatin were randomized 1:1 to receive either FOLFIRI + pbo or FOLFIRI + Afl 4 mg/kg IV Q2W with stratification by ECOG performance score (PS, 0 v 1 v 2) and prior B. OS and progression-free survival (PFS) in the prior B-treated pts are reported as median estimate and hazard ratios (HRs); 95.34% CI for OS and 95% CI for PFS.
Results: Of the 1226 pts in the overall study, 187 in the pbo and 186 in the Afl group were stratified to prior B. The 2 arms were well balanced: median age 60 yrs; male 58%; PS 0-1 97%; and 55% >1 metastatic organ. Although not powered for survival, Afl produced a consistent trend towards prolonged OS and PFS, regardless of prior B use, with no evidence of interaction (OS, P=0.7231; PFS, P=0.6954). The incidence of treatment-emergent adverse events in the Afl arm was similar in pts with prior B (100%) to those without (98.9%), with a similar incidence of grade 3/4 events (82.5% and 83.9%, respectively).
Conclusions: Results of this pre-specified subgroup analysis indicate that adding Afl to FOLFIRI resulted in a consistent trend of increased OS and PFS, regardless of prior B use. Prior treatment with B did not appear to impact the safety profile of Afl.
摘要号：3502
题目：Phase III CORRECT trial of regorafenib in metastatic colorectal cancer (mCRC).
regorafenib 治疗转移性结直肠癌(mCRC)的III期CORRECT研究
摘要：
Background: Regorafenib (REG) is an oral multi-kinase inhibitor. The CORRECT trial was conducted to evaluate REG in patients (pts) with mCRC who had progressed after all approved standard therapies.
Methods: Enrollment criteria included documented mCRC and progression during or ≤3 months after last standard therapy. Pts were randomized 2:1 to receive best supportive care plus either REG (160 mg od po, 3 wks on/1 wk off) or placebo (PL). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, disease control rate, safety and quality of life (QoL). Efficacy analyses across prespecified subgroups were evaluated using univariate Cox regression.
Results: 760 pts were randomized (REG: 505; PL: 255). The OS primary endpoint was met at a preplanned interim analysis. OS and PFS were significantly improved in REG arm compared to PL arm: hazard ratio (HR) for OS 0.77 (95% CI 0.64-0.94, 1-sided p=0.0052), median OS 6.4 vs 5.0 mos; HR for PFS 0.49 (95% CI 0.42-0.58, 1-sided p<0.000001), median PFS 1.9 vs 1.7 mos. Comparable OS and PFS benefits were observed in exploratory subgroup analyses by region, age, time from diagnosis of mCRC to randomization, prior lines of treatment, and KRAS status (shown in table). The most common grade 3+ AEs related to REG were hand-foot skin reaction (16.6%), fatigue (9.6%), hypertension (7.2%), diarrhea (7.2%) and rash/desquamation (5.8%). QoL data will be presented.
Conclusions: REG demonstrated statistically significant improvement in OS and PFS over PL, as well as comparable efficacy benefits across pt subgroups analyzed.
摘要号：LBA4003
题目：Phase III randomized trial of definitive chemoradiotherapy (CRT) with FOLFOX or cisplatin and fluorouracil in esophageal cancer (EC): Final results of the PRODIGE 5/ACCORD 17 trial.
放疗联合FOLFOX或顺铂加氟尿嘧啶(CRT) 治疗食管癌(EC)的III期随机研究：PRODIGE 5/ACCORD17试验的最终结果
摘要：
Background: CRT is one of the best treatment options for localized EC. As new combinations are required to improve safety and survival, we launched a randomized phase II study to assess the complete response (CR) rate of CRT with FOLFOX versus 5FU/cisplatin in 97 pts with localized EC (Conroy 2010). The trial having met its objectives, it has been pursued as a phase III trial. Stratified randomization was performed centrally in a 1:1 ratio according to histological type, pretreatment weight loss in the prior 6 months (<10% vs ≥10%), ECOG PS (0 vs 1 vs 2), and center.
Methods: Pts with technically unresectable cancer or those with surgical contraindications or who refused to undergo surgery were eligible. Eligibility criteria also included age >18 years (y), PS ≤ 2, previously untreated adenocarcinoma or squamous cell EC (any T, N0 or N1, M0 or M1a). The radiation dose was 50 Gy (2Gy/fr) 5 d/wk for 5 wks in both arms. In Arm A, pts received 6 bimonthly cycles (cy): oxaliplatin 85 mg/m2 d1 and leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 bolus d1 then 1,600 mg/m2 46h continuous infusion (ci) ; the first 3 cy were delivered during RT, the 3 other after. In Arm B, pts received 4 cy: cisplatin 75 mg/m2 d1 followed by 5FU 1,000 mg/m2/d ci d1-4, the first 2 cy during RT and 2 other after. The primary endpoint was PFS. Main secondary endpoints were OS, grade 3-4 toxicities, and quality of life. A total of 266 pts would provide 90% power to detect a 20% 3y-PFS difference (α=0.05).
Results: 267 pts were enrolled between 10/2004 and 08/2011. Treatment cohorts were well balanced: male 81%; median age 61 y; PS 0 53%, squamous cell 85.8%, stage III 52%, IVA 6.0% and IVB 3.0%. Full treatment was delivered to 67.9% and 72.2% of pts in arms A/B, respectively. 7 toxic deaths occurred in each arm. Grade 3/4 toxicities per pt (%) in arms A/B were neutropenia 30.6/31.3, febrile neutropenia 5.3/7.0, anemia 5.4/11.0, asthenia 17.6/10.2, respectively. The median FU time was 25.3 mos. 3y-PFS was 18.2/17.4 % (HR=1.07; 95%CI =0.80-1.43) and median OS was 20.2 /17.5 m (HR=1.06; 95%CI =0.77-1.46).
Conclusions: CRT with FOLFOX does not improve PFS compared to cisplatin and 5-FU and has similar toxicities.
摘要号：LBA4000
题目：A randomized multicenter trial of epirubicin, oxaliplatin, and capecitabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3).
一项表阿霉素、奥沙利铂以及卡培他滨(EOC)加或不加帕尼珠单抗治疗初治的晚期食管癌胃癌的随机多中心研究(REAL3)
摘要：
Background: EGFR overexpression occurs in 27-50% of esophagogastric adenocarcinomas (OGA), and correlates with poor prognosis. The REAL3 trial evaluated the addition of the anti-EGFR antibody panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA.
Methods: Patients with untreated, metastatic or locally advanced OGA were randomised to EOC (E 50mg/m2, O 130mg/m2, C 1250mg/m2/day) or mEOC+P (E 50mg/m2, O 100mg/m2, C 1000mg/m2/day, P 9mg/kg). Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response rate (RR), toxicity, and biomarker evaluation. Response was evaluated by RECIST after 4 and 8 cycles. Following IDMC review in October 2011 trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint.
Results: 553 patients were recruited (EOC 275, mEOC+P 278), with median follow-up 5.0 and 5.2 months respectively. Median OS was 11.3 months with EOC compared to 8.8 months with mEOC+P (HR 1.37: 95% CI 1.07-1.76, p=0.013). Median PFS was 7.4 and 6.0 months respectively (HR 1.22: 95% CI 0.98-1.52, p=0.068), with RR being 42% compared to 46% (odds ratio 1.16: 95% CI 0.81-1.57, p=0.467). mEOC+P was associated with ↑ G3/4 diarrhoea (17% vs 11%), skin rash (14% vs 1%) and thrombotic events (12% vs 7%), but ↓ haem toxicity (>G3 neutropenia 14% vs 31%). In the mEOC+P arm, OS was significantly improved in patients with G1-3 rash (77%, n=209) on treatment compared to those without (23%, n=63); median OS 10.2 vs 4.3 months (p<0.001), with similar significant improvements seen in RR and PFS. Biomarker analysis in the first 200 patients has not identified other predictive markers associated with P therapy. Multivariate analysis for OS in these patients demonstrated a negatively prognostic role for KRAS mutation (HR 2.1: 95% CI 1.10-4.05, p=0.025) and PIK3CA mutation (HR 3.2: 95% CI 1.01-10.40, p=0.048).
Conclusions: Addition of P to EOC chemotherapy was associated with worsening of OS in an unselected advanced OGA population. This may be in part due to lowered doses of O and C in the mEOC+P regimen. Outcomes in patients treated with P varied by grade of skin toxicity.
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