Immune checkpoint inhibitors (ICIs), as one of relatively advanced antitumor treatment methods in recent years, have achieved significant therapeutic effects in the treatment of multiple systemic tumors. However, their application in gastrointestinal tumors is not satisfactory, with treatment bottlenecks. This article summarizes the challenges and possible solutions faced by ICIs in the treatment of gastrointestinal tumors to help clinicians better understand the limitations and future development directions of ICIs and thus develop more effective treatment strategies.

背景 目前免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)已成为晚期胃癌的一线及三线的标准治疗药物,但在二线治疗中仅被推荐用于伴有微卫星高度不稳定(MSI-H)或错配修复基因缺陷的患者,因此ICIs在晚期胃癌二线中的治疗模式需要更多的探索.目的 分析ICIs联合化疗、抗血管生成药物二线治疗晚期胃癌及胃食管结合部腺癌患者的疗效.方法 收集 2018年 6月-2022年 1月在解放军总医院第一医学中心二线行ICIs联合化疗、抗血管生成药物治疗的晚期胃癌或胃食管结合部腺癌患者的临床资料,分析入组患者的中位无进展生存期(median progression-free survival,mPFS)、客观缓解率(objective response rate,ORR)及疾病控制率(disease control rate,DCR).采用Kaplan-Meier法绘制生存曲线,并使用Cox回归分析影响mPFS的预后因素.结果 本研究共纳入 49例患者,其中男性 34例,女性 15例,中位年龄 54岁.在二线治疗中,ICIs为纳武利尤单抗或信迪利单抗,27例患者应用纳武利尤单抗,22例应用信迪利单抗.28例患者联合以紫杉醇(白蛋白结合型)为主的方案,21例联合阿帕替尼,6例联合以铂类为主的方案,5例联合以伊立替康为主的方案.69.4%患者选择了免疫药物联合两种及以上抗肿瘤药物的治疗方案.全组患者的ORR为 28.5%,DCR为 89.8%,mPFS为4.7(95%CI:3.830～5.570)个月.多因素Cox分析示,无腹膜转移患者mPFS显著优于有腹膜转移患者(HR=0.410,95%CI:0.197～0.854,P=0.017),一线未应用免疫治疗患者的mPFS显著优于一线应用免疫治疗的患者(HR=0.518,95%CI:0.272～0.987,P=0.045),二线联合≥2种治疗药物患者的mPFS显著优于联合 1种治疗药物的患者(HR=0.454,95%CI:0.231～0.890,P=0.021).结论 晚期胃癌及胃食管结合部腺癌患者二线应用ICIs联合化疗、抗血管生成药物可能提高患者治疗的有效率,延长无进展生存时间.

The combination of immune checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) manifested high efficacy in uHCC. Anlotinib was a novel oral multi-targeted TKI selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Penpulimab, a humanized anti-PD-1 IgG1 monoclonal antibody, was engineered to eliminate FcγR binding, consequently eliminating ADCC, ADCP and ADCR effects. This AK105-203 trial (NCT04172571) aimed to explore the efficacy and safety of penpulimab plus anlotinib in patients (pts) with histologically or cytologically confirmed uHCC.

306 Background: Combined therapy of an immune checkpoint inhibitor with a targeted antiangiogenic agent had been proved to be effective for the treatment of uHCC. Penpulimab was engineered to eliminate FcγR binding and ADCC/ADCP completely, where ADCC/ADCP effects could induce T-cell apoptosis and clearance and then compromise anti-tumor activity. Penpulimab demonstrated a slower PD-1 antigen binding off-rate, which resulted in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody and might contribute to slower binding off-rate. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of penpulimab. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Methods: In this open-label, multicenter phase Ib/II study, patients (pts) without prior systemic treatment, and classified as BCLC stage B (not amenable for locoregional therapy) or C, Child-Pugh ≤7, and ECOG PS ≤ 1 received Penpulimab (200mg IV Q3W) and Anotinib (8 mg PO 2weeks on/1 week off). Primary endpoint was ORR (RECIST v1.1); secondary endpoints were safety, DCR, DoR, TTP, PFS and OS. Results: 31 pts (median age 56 years [23–74], ECOG 0/1 [64%/36%], BCLC B/C [23%/77%], HBV/HCV [61%/7%]) received combined therapy. As of August 31, 2020, median follow-up time was 11.9 mons (range 3.7-17.7). Median PFS was 7.6 mons with 6-mons PFS rate was 57.6% while median TTP was 8.5 mons with 6-mons TTP rate was 62.7%. Median overall survival had not been met and 6-mons OS rate was 93.2%. The ORR was 31.0% (9/29) and DCR was 82.8% (24/29). At data cutoff, 77.8% of responders remained ongoing and still on treatment. Treatment-related adverse events (TRAEs) occurred in 90.3% of pts (≥G3 in 16.1% [5/31], no G5, treatment discontinuation in 9.7% [3/31]). Most common TRAEs (≥15%) were increased AST (38.7%) and ALT (35.5%), increased blood bilirubin (22.6%),asthenia (22.6%),decreased platelet count (19.4%) and rash (16.1%). Conclusions: Penpulimab plus Anlotinib showed favorable antitumor efficacy and an acceptable safety profile in pts with uHCC. The further randomized, phase 3 study of Penpulimab in combination with Anlotinib at a higher dose (10 mg PO 2 weeks on/1 week off) in this setting is ongoing (NCT04344158).

背景 尼妥珠单抗是以表皮生长因子受体(epidermal growth factor receptor,EGFR)为靶点的靶向药物,在国外的临床研究中取得良好的效果,但国内大规模的临床试验数据相对较少.目的 探讨尼妥珠单抗联合吉西他滨(gemcitabine,GEM)一线治疗晚期胰腺癌的疗效和安全性.方法 通过解放军总医院大数据平台,检索2012年1月-2019年6月在解放军总医院第一医学中心治疗的晚期胰腺癌患者的临床资料,根据不同治疗方案,通过倾向性匹配,共纳入122例晚期胰腺癌患者,联合组61例采用尼妥珠单抗+GEM,单药组61例采用GEM单药化疗.比较两组患者的一般资料、不良反应发生率、无进展生存期(progression free survival,PFS)和总生存期(overall survival,OS).结果 联合组PFS优于单药组(4.5个月vs 3.1个月,P<0.001);联合组OS也高于单药组(7.4个月vs 6.4个月,P<0.001).多因素分析显示,GEM联合尼妥珠单抗一线治疗晚期胰腺癌可延长晚期胰腺癌患者的生存期(P<0.001).两组间与治疗相关的不良事件发生率无统计学差异(P>0.05).结论 与GEM单药相比,尼妥珠单抗联合GEM一线治疗晚期胰腺癌可增加患者的生存获益,且未增加不良反应,对于晚期胰腺癌患者来说是一个可供选择的一线治疗方案.

1 病例资料 患者,女,73岁,因右半结肠切除术后5年余,肝转移复发综合治疗3年余,发现新发肝占位性病变10余天,于2019年10月就诊于解放军总医院第一医学中心. 患者于2014年3月初无明显诱因出现排便习惯改变,于当地医院行肠镜检查,提示"结肠占位".2014年4月30日至北京协和医院行经腹腔镜右半结肠切除术,术后病理诊断示:结肠中分化腺癌,部分为黏液腺癌,浸透肌层达周围脂肪组织,肠周脂肪组织中可见癌结节形成.淋巴结未见转移癌(结肠中动脉根部0/1、回结肠动脉根0/7、肠系膜上静脉周围0/4、结肠周围0/19).

Objective This study aims to assess the efficacy and safety of penpulimab (a humanized anti-PD-1 IgG1 antibody) with anlotinib in the first-line treatment of Chinese patients with uHCC. Methods In this open-label multicenter phase Ib/II trial, patients with histologically or cytologically confirmed uHCC, without previous systemic treatment, aged 18–75 years old, classified as BCLC stage B (not amenable for locoregional therapy) or C, with Child–Pugh score ≤7 and ECOG performance status ≤1 were enrolled. Patients received penpulimab [200 mg intravenous (i.v.) Q3W] and oral anlotinib (8 mg/day, 2 weeks on/1 week off). The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), duration of response (DoR), and overall survival (OS). This trial is registered with ClinicalTrials.gov (NCT04172571). Results At the data cutoff (December 30, 2020), 31 eligible patients had been enrolled and treated with a median follow-up of 14.7 months (range, 1.4–22.1). The ORR was 31.0% (95% CI, 15.3–50.8%), and the DCR was 82.8% (95% CI, 64.2–94.2%). The median PFS and TTP for 31 patients were 8.8 months (95% CI, 4.0–12.3) and 8.8 months (95% CI, 4.0–12.9) respectively. The median OS was not reached; the 12-month OS rate was 69.0% (95% CI, 48.9–82.5%). Only 19.4% (6/31) of patients had grade 3/4 treatment-related adverse events (TRAEs). Conclusion Penpulimab plus anlotinib showed promising anti-tumor activity and a favorable safety profile as first-line treatment of patients with uHCC.

目的 观察安罗替尼联合PD-1单抗(AK105)治疗晚期转移性肝细胞癌的疗效和不良反应.方法 选取2019年1-8月在我科使用安罗替尼联合PD-1单抗治疗的13例晚期原发性肝癌患者的临床资料,观察疗效及不良反应.随访时间截至2019年9月27日,结果安罗替尼联合PD-1单抗(AK105)治疗晚期转移性肝癌主要不良反应为手足综合征、皮肤反应及高血压等,未出现3～4级不良反应.13例患者中,3例达到了部分缓解,6例获得了疾病稳定,客观缓解率为23.1％,疾病控制率为69.2％.结论 我们的初步研究显示安罗替尼联合PD-1单抗治疗晚期转移性肝癌不良反应可控,具有较好的疗效.

Immune checkpoint inhibitors (ICIs) represent a major breakthrough for cancer treatment. However, evidence regarding the use of ICIs in pancreatic cancer (PC) remained scarce. To assess the efficacy and safety of ICIs plus chemotherapy, patients with advanced PC were retrospectively recruited and were treated with either chemotherapy alone or chemotherapy plus ICIs. Patients previously treated with any agents targeting T-cell co-stimulation or checkpoint pathways were excluded. The primary outcome was overall survival (OS). The secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and safety. In total, 58 patients were included (combination, n = 22; chemotherapy, n = 36). The combination group showed a significantly longer OS than the chemotherapy group [median, 18.1 vs 6.1 months, hazard ratio (HR) 0.46 (0.23–0.90), P = 0.021]. The median PFSs were 3.2 months in the combination group and 2.0 months in the chemotherapy group [HR 0.57 (0.32–0.99), P = 0.041]. The combination group and the chemotherapy group had similar ORRs (18.2% vs 19.4%, P = 0.906). All patients who achieved a partial response received a doublet chemotherapy regimen regardless of co-treatment with ICIs. Grade 3 or higher adverse events occurred in 31.8% of the patients in the combination group and in 16.9% of those receiving chemotherapy. Although the incidence of serious treatment-related adverse events was higher in the combination group than in the chemotherapy group, the difference was not significant ( P = 0.183). Our findings suggest that the combination of ICIs with chemotherapy is both effective and tolerable for advanced PC. ICIs combined with a doublet chemotherapy regimen might be a preferable choice.

4592 Background: Advanced HCC is a deadly disease with few systemic therapeutic options. VEGF blockade potentiates the effect of PD-1 inhibition by opposing the immunosuppressive effects of VEGF-A (increased DC maturation, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors). A sBLA has been submitted for an anti-PD-L1 + anti-VEGF combination as 1L treatment for advanced HCC. Penpulimab is a novel humanized anti-PD-1 IgG1 antibody with complete removal of Fc receptor mediated effect, and featuring slow antigen binding off-rate and high receptor occupancy. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Methods: In this open-label, multicenter phase Ib/II study, treatment-naive pts with advanced HCC received penpulimab 200mg Q3W in combination with anlotinib 8mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary objectives were to assess antitumor activity by ORR (RECIST v1.1). The secondary objectives were to assess antitumor activity by DCR, DoR, TTP, and to assess the safety and tolerability of the combination. Results: As of Jan 14, 2020, 31 pts (median age 56 years [23-74], male 81%, ECOG 0/1 [64%/36%], BCLC B/C [23%/77%], HBV/HCV [61%/7%]) received combined therapy (a median of 6 [1-15] doses). Treatment-related adverse events (TRAEs) occurred in 93.5% of pts (G3 in 9.7% [3/31], no G4, and leading to treatment discontinuation in 6.5% [2/31]). Most frequent TRAEs were increased AST (35.5%), increased ALT (29%), asthenia (22.6%), decreased platelet count (19.4%), increased blood bilirubin (19.4%), increased bilirubin conjugated (19.4%), and rash (16.1%). Of 25 evaluable pts (with the opportunity to be followed-up for ≥2 scans, 12 weeks), confirmed ORR was 24% (6/25) and DCR was 84% (21/25). Five responders remained in response with DoR ranging 1.4+ to 6.9+ months. Median TTP was not reached and 6m-TTP rate was 63% (95% CI: 38%, 81%). Conclusions: Penpulimab in combination with anlotinib had a manageable safety profile and encouraging antitumor activities in patients with advanced HCC. No unexpected AEs were identified beyond the established safety profile for each agent. Evaluation of penpulimab + anlotinib (10 mg QD) in a phase 3 study for 1L HCC is currently underway. Clinical trial information: NCT04172571 .

e14100 Background: Biliary tract cancer (BTC) is highly aggressive with poor prognosis and few treatment options following progression on gemcitabine-based chemotherapy. Disappointing results from clinical trials for refractory BTC highlight the need for more effective therapies. Immune checkpoint inhibitor (ICI) has been hailed as a major breakthrough for cancer treatment. However, evidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory. KEYNOTE-158 trial has merely shown a 5.8% of overall response rate with pembrolizumab monotherapy in advanced BTCs. Thus, combining other therapies with ICIs is becoming the researching focus. Herein, we constructed a cohort to evaluate the efficacy and safety of ICIs combined with chemotherapy in advanced BTCs. Methods: Chinese BTC patients receiving PD-1 inhibitors with chemotherapy, PD-1 inhibitors monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcome were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T-cell co-stimulation or immune checkpoints were excluded. Results: The study included 77 patients (PD-1 inhibitors plus chemotherapy, n = 38; PD-1 inhibitors monotherapy, n = 20; chemotherapy, n = 19). Median OS was 14.9 months with PD-1 inhibitors plus chemotherapy, 4.1 months with PD-1 inhibitors and 6.0 months with chemotherapy, with significantly longer for anti-PD-1 combination therapy than monotherapy (HR 0.37, 95% CI 0.17-0.80, P= 0.001) or chemotherapy (HR 0.63, 95% CI 0.42-0.94, P= 0.011). Median PFS was 5.1 months with PD-1 inhibitors plus chemotherapy, 2.2 months with PD-1 inhibitors and 2.4 months with chemotherapy, with significant difference for anti-PD-1 combination therapy versus anti-PD-1 monotherapy (HR 0.59, 95% CI 0.31-1.10, P= 0.014) or chemotherapy (HR 0.61, 95% CI 0.45-0.83, P= 0.003). Grade 3 or 4 treatment-related adverse events were similar between anti-PD-1 combination group and chemotherapy group (34.2% and 36.8%). Conclusions: PD-1 inhibitors plus chemotherapy is effective and tolerable for advanced BTC.

e14103 Background: Pancreatic cancer (PC) is a highly lethal disease and characterized by a strong resistance to current radiotherapy and chemotherapy. As PC has the presence of a microenvironment filled with immunosuppressive mediators and a dense stroma which involved in immune system control, the immune system has been hypothesized to play an important role in PC. However, there was no response in patients who received immune checkpoint inhibitors (ICIs) monotherapy. Though small sample studies revealed that ICIs combined with chemotherapy is effective, a head-to-head comparison of ICIs plus chemotherapy and chemotherapy is limited. Methods: Advanced PC patients treated with chemotherapy alone or plus ICIs were retrospectively screened for eligibility. Patients previously treated with any agent targeting T-cell co-stimulation or checkpoint pathways was excluded. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and safety. Results: In total, 58 patients were included (combination, n = 22; chemotherapy, n = 36). Combination group presented significantly longer OS than chemotherapy group (median, 18.1 vs 6.1 months, HR 0.46 [0.23-0.90], P = 0.021). Median PFS was 3.2 months in the combination group and 2.0 months in the chemotherapy group (HR 0.57 [0.32-0.99], P = 0.041). The ORR was similar between the combination group and the chemotherapy group with no significant difference (18.2% vs 19.4%, P = 0.906). And all the patients, who reached partial response, accepted a two-chemotherapic-drugs regimen regardless of combinating with ICIs. Adverse events of grade 3 or higher occurred in 31.8% of the patients in the combination group and in 16.9% of those in the chemotherapy group. Though the incidence rate of serious treatment-related adverse events (TRAEs) was higher in the combination group than the chemotherapy group, no statistical significance existed (P = 0.183). Conclusions: Combination of ICIs plus chemotherapy is effective and tolerable for advanced PC. Accepting ICIs combined with a two-drug chemotherapy regimen might be the better choice.

Background Evidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory. Methods Chinese BTC patients receiving a PD-1 inhibitor with chemotherapy, PD-1 inhibitor monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcomes were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T cell costimulation or immune checkpoints were excluded. Results The study included 77 patients (a PD-1 inhibitor plus chemotherapy, n = 38; PD-1 inhibitor monotherapy, n = 20; chemotherapy alone, n = 19). The median OS was 14.9 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 4.1 months with PD-1 inhibitor monotherapy (HR 0.37, 95% CI 0.17–0.80, P = 0.001) and the 6.0 months with chemotherapy alone (HR 0.63, 95% CI 0.42–0.94, P = 0.011). The median PFS was 5.1 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 2.2 months with PD-1 inhibitor monotherapy (HR 0.59, 95% CI 0.31–1.10, P = 0.014) and the 2.4 months with chemotherapy alone (HR 0.61, 95% CI 0.45–0.83, P = 0.003). Grade 3 or 4 treatment-related adverse events were similar between the anti-PD-1 combination group and the chemotherapy alone group (34.2% and 36.8%, respectively). Conclusions Anti-PD-1 therapy plus chemotherapy is an effective and tolerable approach for advanced BTC.

Abstract Immune checkpoint blockade‐related pneumonitis is a rare but potentially life‐threatening adverse effect, but its risk factors are not completely understood. This case‐control study was conducted to identify pneumonitis risk factors in patients treated with anti‐PD1 monoclonal antibodies (mAbs), including all the patients who developed pneumonitis after anti‐PD‐1 mAbs treatment in the Cancer Center of the Chinese People's Liberation Army from September 2015 to September 2017. Two controls per case were matched according to a propensity‐score matching algorithm to account for confounding effects caused by individual baseline variables. Demographic and clinical information was obtained from medical records. In total, 55 cases and 110 controls were included in the study. No association was observed between smoking status or primary lung cancer and risk of pneumonitis. Significant risk factors for pneumonitis related to anti‐PD‐1 mAbs were prior thoracic radiotherapy, prior lung disease and combination therapy with odds ratios of 3.34 (1.51‐7.39), 2.86 (1.45‐5.64) and 2.73 (1.40‐5.31), respectively. The associations remained significant in the multivariable logistic regression model. The risk of pneumonitis induced by anti‐PD‐1 mAbs is associated with prior thoracic radiotherapy, prior lung disease, and combination therapy. Clinicians should monitor these features in patients receiving anti‐PD‐1 therapy to optimize clinical safety and efficacy.

e15132 Background: Despite its great efficacy in patients with solid tumors, immune checkpoint blockade (ICB) might also lead to a series of inflammatory effects known as immune-related adverse events (irAEs) as results of imbalance of immune system homeostasis. Of these, ICB-related pneumonitis may be infrequent but potentially life-threatening. Previous studies have clarified the clinical features, diagnosis and management of ICBs related-pneumonitis thoroughly, nevertheless, the risk factors of ICBs-related pneumonitis are poorly studied directly. Methods: This case-control study was proposed to describe the clinical features and identify the risk factors for ICB-related pneumonitis in patients undergoing anti-PD1 therapy. All patients who developed pneumonitis during the treatment in the Cancer Center of the Chinese People’s Liberation Army from September 2015 to September 2017 were included. Two controls per case were matched in accordance with a propensity-score matching algorithm that accounted for confounding effects of individual baseline variables. Demographic and clinical features were extracted from their medical records. Results: In total, 55 cases and 110 controls were included in this study. The onset time of pneumonitis ranged from 2 to 277 days (median: 85 days). Of these, 85.7% of patients were resolved/improved via steroid therapy (12 of 14). No association was observed between risk of pneumonitis and smoking status or primary lung cancer. Significant risk factors for the pneumonitis induced by anti-PD-1 therapy contained: prior thoracic radiotherapy, underlying lung condition and combination therapy with odds ratios of 3.34 (1.51-7.39), 2.86 (1.45-5.64) and 2.73 (1.40-5.31) respectively. In multivariate logistic regression analysis, prior thoracic radiotherapy, combination therapy and underlying lung condition were significantly related to the risk of pneumonitis. Conclusions: Risk of anti-PD-1-related pneumonitis is associated with prior thoracic radiotherapy, underlying lung condition and combination therapy. Clinicians should beware of these characteristics in patients receiving anti-PD-1 immunotherapy to optimize clinical safety and efficacy.

Apatinib has been proved to be effective and safe among patients in gastric cancer in Phase II and III Trials. We aimed to evaluate its efficacy and safety in real world practice, and to explore factors associated with efficacy. Between January 2015 and February 2017, totally 36 patients with advanced gastric adenocarcinoma or adenocarcinoma of gastroesophageal junction (GEJ) were enrolled and followed up retrospectively after failing at least two lines of systemic therapy. The mPFS was 2.65 months (95%CI 1.66–3.54), and mOS was 5.8 months (95%CI 4.77–6.83). Two patients achieved partial response, and nineteen achieved stable disease. The disease control rate (DCR) was 58.3%, and objective response rate (ORR) was 5.6%. Common grade adverse events were hypertension (38.9%), proteinuria (36.1%), and neutropenia (33.3%). And the most common adverse events over grade 3 were hand-foot syndrome (8.3%), anemia (5.6%), and diarrhea (5.6%). No treatment-related death was documented during the drug administration. Exploratory analyses indicated patients treated with antiangiogenic therapy previously were more likely to benefit from apatinib.

Apatinib has been proven to be effective and safe among patients in the third-line treatment of advanced gastric cancer in phase II and III trials. We aimed to evaluate its efficacy and safety in second-line practice, and to explore the factors associated with efficacy. Between April 2015 and May 2017, a total of 23 patients with advanced gastric adenocarcinoma or adenocarcinoma of gastroesophageal junction were enrolled and followed up retrospectively after failing the first line of systemic therapy. The median progression-free survival was 4.43 months (95% confidence interval: 1.63-7.22) and the median overall survival was 9.11 months (95% confidence interval: 8.22-9.99). Two patients achieved a partial response and 14 patients achieved stable disease. The disease control rate was 69.6% and the objective response rate was 8.7%. The most common adverse events over grade 3 were hypertension (8.7%) and thrombocytopenia (8.7%). No treatment-related death was documented during the drug administration. Apatinib is an effective regimen for the second-line treatment of advanced gastric and gastroesophageal cancer with manageable toxicity.

Objective:To investigate the clinical features, treatment and prognosis of colorectal carcinoma with BRAF mutation. Methods: A total of 12 patients from 2010 to 2015 were treated for advanced colorectal cancer with BRAF mutation in the PLA General Hospital. Clinical data were retrospectively analyzed.Results:7 patients with BRAF mutation were male (58.3%), 5 patients were female (41.7%). All the patients were above 40 years old. 2 patients (16.7%) had colorectal carcinoma with BRAF mutation in the right colon, 10 (83.3%) in left colon and rectum. 10 patients had adenocarcinoma and 2 patients had mixed type of adenocarcinoma and mucinous carcinoma. There were 6 cases with moderate differentiation and low differentiation respectively. Immunohistochemical detections of 8 cases with DNA mismatch repair gene immunization are microsatellite stable type. First-line treatment objective response rate was 27.3%and disease control rate was 72.7%. The median PFS was only 16.4 weeks and the median OS 32 weeks.Conclusion:BRAF mutations are more common in the elderly, patients with poor differentiation and the left half of colon tumor. As a special type of colorectal carcinoma, its ifrst-line chemotherapy sensitivity and prognosis are poor.

ObjectiveTo investigate the efficacy and safety of cetuximab with FOLFIRI or FOLFOX/XELOX as first-line chemotherapy for patients with K-RAS wild-type advanced colorectal cancer.MethodsClinical data about 98 histopathology confirmed patients with KRAS wild-type advanced colorectal cancer admitted to our hospital from February 2008 to July 2014 were collected and analyzed. Forty-four patients received cetuximab plus FOLFOX/XELOX, 54 patients received cetuximab plus FOLFIRI. Each patient received at least two cycles of chemotherapy, every 6 weeks for evaluation. The efficacy was evaluated according to RECIST 1.1.ResultsNinety-eight patients were available for evaluation. In cetuximab plus FOLFOX/XELOX group, the complete response (CR) was 2.27%, partial response (PR) was 63.64%, stable disease (SD) was 25%, and progressive disease (PD) was 9.09%. In cetuximab plus FOLFIRI group, CR was 0%, PR was 40.74%, SD was 44.45%, PD was 14.81%. The objective response rate (ORR) of these two groups were 65.91% and 40.74%, respectively, which was of statistically significant difference (P=0.013). The disease control rate (DCR) were 90.91% and 85.19% respectively, which showed statisticallysignificant difference (P=0.390). The median progression-free survival (PFS) was 8.4 months and 7.7 months respectively, with no statistically significant differences (P=0.580).ConclusionThe efficacy of addition of cetuximab to oxaliplatin-based chemotherapy infirst-line treatment for K-RAS wild-type advanced colorectal cancer is not inferior to cetuximab combined with FOLFIRI regimen. Adverse reactions show no significant difference between the two groups, which suggests that it is worthy of promotion.

OBJECTIVE:To observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma.METHODS:Clinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology, Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods.RESULTS:The disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9% (61/71) vs. 59.3% (16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1% (41/45) vs. 68.1% (32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However, the differences were not statistically significant (P>0.05).CONCLUSIONS:Cetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.