A consensus on immunotherapy from the 2017 Chinese Lung Cancer Summit expert panel.

The notable clinical success of cancer immunotherapy using checkpoint blockade suggests that it is likely to form the foundation of curative therapy for many malignancies. However, checkpoint blockades do not achieve sustained clinical response in most patients and thus amounts of problems needed to be figured out. Regarding these challenges, the 2017 Chinese Lung Cancer Summit expert panel organized a forum on the 14th Chinese Lung Cancer Summit to formally discuss these controversies. Five consensuses finally were reached to guide the application of checkpoint blockades.

Capecitabine/cisplatin versus 5-fluorouracil/cisplatin in Chinese patients with advanced and metastatic gastric cancer: Re-analysis of efficacy and safety data from the ML17032 phase III clinical trial.

AIM: To confirm non-inferiority and test potential superiority of capecitabine/cisplatin (XP) over 5-fluorouracil (5-FU)/cisplatin (FP) as first-line treatment for advanced gastric cancer (AGC) in Chinese patients. METHODS: In open-label phase III ML17032 trial, AGC (stage IIIA-IV) patients with or without metastases were randomized 1:1 to receive cisplatin (80 mg/m2 /day intravenous [IV] day 1) with either capecitabine (1000 mg/m2 /day oral [PO] twice daily [BID], days 1-14; XP) or 5-FU (800 mg/m2 /day continuous IV days 1-5; FP) every 3 weeks. The primary objective was to confirm the non-inferiority of XP over FP for progression-free survival (PFS). RESULTS: The intent-to-treat (ITT) population included 126 Chinese patients (XP-62, FP-64; 67.5% male, mean age 54.7 years). The primary analysis was performed on the per-protocol (PP) population (105 patients; XP-51, FP-54; 65.7% male). Median PFS in the XP and FP groups was 7.2 and 4.5 months, respectively. The adjusted hazard ratio (HR) for PFS was 0.52 (95% confidence interval [CI]: 0.32-0.83, P = 0.006). Unadjusted HR for PFS in the ITT population was 0.63 (95% CI, 0.42-0.94, P = 0.022). The most frequent drug-related grade 3/4 adverse events (AEs) were neutropenia (XP-20.7%, FP-17.7%) and gastrointestinal disorders (XP-19.0%, FP-19.4%). The overall incidence of grade 3/4 AEs (XP-43.1%, FP-46.8%), serious AEs (XP-1.7%, FP-3.2%), and AEs related to treatment discontinuation (XP-10.3%, FP-16.1%) were comparable. CONCLUSION: XP had a similar safety profile and may demonstrate superiority for PFS compared to FP as first-line treatment of Chinese patients with AGC (NCT02563054).

A consensus on liquid biopsy from the 2016 Chinese Lung Cancer Summit expert panel.

The diagnosis and treatment of lung cancer have evolved into the era of precision medicine. Liquid biopsy, a minimally invasive approach, has emerged as a promising practice in genetic profiling and monitoring of lung cancer. Translating liquid biopsy from bench to bedside has encountered various challenges, including technique selection, protocol standardisation, data analysis and cost management. Regarding these challenges, the 2016 Chinese Lung Cancer Summit expert panel organised a trilateral forum involving oncologists, clinicians, clinical researchers, and industrial expertise on the 13th Chinese Lung Cancer Summit to formally discuss these controversies. Six consensuses were reached to guide the use of liquid biopsy and perform precision medicine in both clinic and research.

Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study.

BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

Expression of BAFF-R, but not BAFF, is an independent prognostic factor in diffuse large B-cell lymphoma patients treated with R-CHOP.

B-cell activating factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the progression of malignant B-cells. The aim of the present study was to evaluate the expression profiles and the clinical significance of BAFF and BAFF-R in diffuse large B-cell lymphoma (DLBCL). Paraffin-embedded specimens from 136 patients with newly diagnosed DLBCL, treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP), were examined for BAFF and BAFF-R expression by immunohistochemistry. BAFF and BAFF-R were expressed in 72.1 % (98/136) and 47.1 % (64/136) of the DLBCL tissues, respectively. Negative BAFF-R expression was significantly correlated with elevated serum lactate dehydrogenase (LDH) levels (P = 0.036), an International Prognostic Index (IPI) score of 2 or higher (P < 0.001), and a poor revised IPI (R-IPI) risk score (P = 0.043). The complete response rate after R-CHOP was higher in patients with positive BAFF-R expression than in those with negative BAFF-R expression (73.4 vs. 56.9 %, P = 0.045). Negative expression of BAFF-R, but not of BAFF, was significantly associated with inferior progression-free survival (PFS; P = 0.020) and overall survival (OS; P = 0.028). Only negative BAFF-R expression was correlated with inferior PFS and OS in multivariate analysis (P = 0.049 and 0.040, respectively). Taken together, our results showed that the majority and approximate one-half of patients with DLBCL were positive for BAFF and BAFF-R, respectively. Negative expression of BAFF-R, but not of BAFF, could be an independent risk factor for PFS and OS in patients with DLBCL treated with standard R-CHOP.

A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers.

INTRODUCTION: The aim of this study was to compare the efficacy and toxicity of dicycloplatin plus paclitaxel with those of carboplatin plus paclitaxel as first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: In this study, 240 NSCLC patients with stage IIIB (with pleural effusion) and stage IV disease were randomly assigned (1: 1) to receive dicycloplatin 450 mg/m(2) or carboplatin AUC = 5, in combination with paclitaxel 175 mg/m(2) (D + P or C + P) every 3 weeks for up to 4 to 6 cycles. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: The response rates for the D + P and C + P arm were 36.44% and 30.51%, respectively (p = 0.33). The median PFS was 5.6 months in the D + P arm and 4.7 months in the C + P arm (p = 0.31). The median OS was 14.9 months for D + P and 12.9 months for C + P (p = 0.37). Adverse events in the two arms were well balanced. The most common grade 3/4 adverse event was hematologic toxicity. CONCLUSIONS: Patients treated with D + P had similar response and survival rates to those treated with C + P, and toxicities of both treatments were generally tolerable.

Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone.

INTRODUCTION: Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA mutations and PTEN low in patients receiving paclitaxel alone or in combination with lapatinib. METHODS: Immunohistochemistry and mutation analyses were used to evaluate PTEN and PIK3CA, respectively. Kaplan-Meier analysis with log-rank tests, logistic regression and Cox models were used in analyses of these biomarkers with efficacy endpoints. RESULTS: In the overall population, PIK3CA mutations were associated with poorer overall survival (OS) (hazard ratio (HR) = 1.87; 95% confidence interval (CI): 1.22, 2.88; P = 0.001). PTEN expression was not associated with OS (P = 0.474). In the PIK3CA wild-type subgroup, lapatinib plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR = 0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not significantly improved within the PIK3CA mutation subgroup (P = 0.179). In the PTEN low group, OS was improved with addition of lapatinib (P = 0.039). In both PTEN subgroups, addition of lapatinib was associated with improvements in PFS (P <0.050). PIK3CA and PTEN were not predictive of treatment based on interaction tests (P >0.05). CONCLUSIONS: PTEN was neither a significant prognostic nor predictive factor. PIK3CA mutations were an adverse prognostic factor for survival but not predictive for lapatinib benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT00281658 (registered 23 January 2006).

Multicenter randomized phase 2 clinical trial of a recombinant human endostatin adenovirus in patients with advanced head and neck carcinoma.

A randomized, open-label, phase 2, multicenter clinical trial was conducted to evaluate the efficacy and safety of the addition of a recombinant human endostatin adenovirus (E10A) to cisplatin and paclitaxel in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 3 weeks for a maximum of six cycles or to receive chemotherapy only. One hundred and thirty-six eligible patients were randomly assigned. The addition of E10A did not significantly improve the objective response rate (29.9 versus 39.7%, P = 0.154). However, patients who received endostatin had longer progression-free survival (7.03 versus 3.60 months, P = 0.006; hazard ratio: 0.55). The combination of E10A with chemotherapy benefited prior chemotherapy-treated patients and those who received three to four treatment cycles (6.50 versus 3.43 months, P = 0.003; 8.27 versus 4.27 months, P = 0.018; respectively). The overall disease control rate significantly increased from 80.6% in the control group to 92.6% in the test group (P = 0.034). Except for fever, no adverse events were associated with the E10A treatment. In summary, E10A plus chemotherapy is a safe and effective therapeutic approach in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma.

[Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. RESULTS: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. CONCLUSIONS: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials.

PURPOSE: his analysis pooled individual patient data from randomized controlled trials (RCTs) to more thoroughly examine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patient data were pooled from the first-line AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second-line E3200 RCT. All analyses were based on the intent-to-treat population. To assess differences in time-to-event variables by treatment (chemotherapy with or without placebo vs. chemotherapy plus bevacizumab), stratified random-effects (overall) and fixed-effects (subgroup comparisons) models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The analysis population comprised 3,763 patients (1,773 chemotherapy with or without placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to chemotherapy was associated with statistically significant increases in overall survival (OS; HR, 0.80; 95% CI, 0.71-0.90) and progression-free survival (PFS; HR, 0.57; 95% CI, 0.46-0.71). The effects on OS and PFS across subgroups defined by chemotherapy backbone (oxaliplatin-based, irinotecan-based), extent of disease (liver metastases only, extensive disease), age (<65, ≥65 years), Eastern Cooperative Oncology Group performance status (0, ≥1), and KRAS status (wild-type, mutant) were consistent with the overall analysis. Incidence rates of grade ≥3 hypertension, proteinuria, bleeding, wound-healing complications, gastrointestinal perforations, and thromboembolic events were increased with bevacizumab treatment. CONCLUSION: The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC. The PFS benefit extended across the clinically relevant subgroups examined. The observed safety profile of bevacizumab was consistent with that reported in individual trials.

Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.

PURPOSE: Lapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC). PATIENTS AND METHODS: This phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety. RESULTS: The addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. CONCLUSION: This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.

Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results.

UNLABELLED: TRANSLATIONAL RELEVANCE: Dicycloplatin (DCP) is a novel super molecule composed of carboplatin (CBP) and 1,1-cyclobutane dicarboxylate (CBDCA) joined by a strong hydrogen bond. The solubility and stability of platinum complexes have a direct bearing on their activity, toxicity and pharmacokinetics. Preclinical studies have shown that DCP overcomes the problem of CBP instability in aqueous solution and maintains anticancer effects. Clinical evaluation in a Phase I dose-escalation study in patients with tumors showed that DCP was tolerated at doses ranging from 100 to 550 mg/m(2) and had potential efficacy in Chinese cancer patients. DCP showed favourable bioavailability and stability in vivo, and the recommended Phase II dosage for DCP-containing chemotherapy is 450 mg/m(2). DCP is currently being investigated as a monotherapy in several cancer types, such as prostatic carcinoma, and in combination with paclitaxel in a Phase II non-lung cancer study. PURPOSE: Dicycloplatin (DCP) is a novel supramolecule composed of carboplatin (CBP) and 1,1-cyclobutane dicarboxylate (CBDCA) joined by a strong hydrogen bond. DCP is stable in aqueous solution unlike CBP alone. The purpose of this study was to assess the maximally tolerated dose, safety, and pharmacokinetics of DCP in Chinese cancer patients. EXPERIMENTAL DESIGN: 29 patients were included in this study. DCP was administered by intravenous infusion over 1 hour once every 21 days. The dose of DCP was escalated from 50 mg/m(2) to 650 mg/m(2) using a modified Fibonacci scheme. Pharmacokinetic analysis was performed in 26 patients to determine the total and ultrafiltered platinum concentrations in plasma. RESULTS: 29 and 20 patients were evaluated for toxicities and response, respectively. The primary adverse effects were nausea/vomiting (58.6%), thrombocytopenia (24.1%), neutropenia (17.2%), anemia (20.7%), fatigue (10.3%), anorexia (10.3%), liver enzyme elevation (10.3%) and alopecia (3.5%). There was no significant toxicity with doses up to 350 mg/m(2). At higher doses, a variety of dose-limiting toxicities (DLTs) were observed, including Grade 3/4 anemia, Grade 3/4 thrombocytopenia, and Grade 3/4 emesis under antiemetic treatment. The maximum tolerated dose of DCP was 550 mg/m(2). Two partial responses occurred in patients with non-cell lung cancer who had received cisplatin- or carboplatin-based chemotherapy. Plasma decay of total and free platinum concentrations was best fitted by using a twocompartment analysis. The terminal plasma half-life of total platinum after DCP administration ranged from 41.86 to 77.20 hours without significant dose dependency. However, the terminal plasma half-life of free platinum concentrations ranged from 42.34 to 61.07 hours. CONCLUSIONS: DCP displayed a favorable safety profile at doses between 50 mg/m(2) and 550 mg/m(2), and first efficacy signals were observed. DLTs were thrombocytopenia, anemia and emesis. The recommended starting dose for a subsequent Phase II study is 450 mg/m(2) once every 3 weeks.

[A study on the long-term non-small cell lung cancer survivors in the Expand Access Program of gefitinib in China].

BACKGROUND AND OBJECTIVE: The Expand Access Program (EAP) of Iressa(gefitinib, ZD1839) in China was initiated in 2001 with the aim of providing gefitinib to non-small cell lung cancer (NSCLC) patients who failed to respond to standard treatment or who could not tolerate chemotherapy. The primary objective was to describe the quality of life (QoL), tumor control status, drug safety, and clinical/genomic features of active long-term survivors enrolled in the EAP. The secondary objective was to determine the clinical characteristics of long-term survivors in the EAP program. METHODS: In this descriptive observational study, data were collected based on epidemiological research methods. The data of patients who were actively participating in the EAP and still undergoing gefitinib treatment were collected in a cross-sectional manner to reflect the current status of each patient. Meanwhile, the data of patients who had been on gefitinib treatment for more than three years and had already been terminated from the EAP or those who were fast progressors were collected retrospectively. RESULTS: A total of 934 patients were screened in the EAP database. Among these patients, 25 were active long-term survivors still enrolled in the EAP and 34 were long-term survivors who had been terminated from the program. These 59 patients were enrolled in 15 different centers in China, and the remaining 875 patients were fast progressors. The median scores for the Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI), and Lung Cancer Subscale (LCS) of the 25 long-term survivors were 64.5, 37 and 12.5, respectively. The performance status 0-1 accounted for 91.6% of the data observed during the cross-sectional survey. For active long-term survivors, the objective response rate was 37.5%, the disease control rate was 87.5%, and the median duration of response time was almost 68 months. In the long-term survivor group, no serious and new adverse events were reported. Patients who were aged under 65 years (68.5%), affected with adenocarcinoma (81.4%), female (55.9%), or had never smoked (71%) accounted for majority of the long-term survivors. The percentage of females was significantly higher in the long-term survivor group than in the fast progressor group (P=0.02). Three tissue samples were collected from each of the 24 active long-term survivors, and one patient was found to be positive of EGFR mutation. Twenty-two blood samples were also collected, and one patient tested positive for EGFR mutation. The Ki67 protein expression was also tested in three tissue samples, and two of these were found positive for Ki67 protein expression, with a response duration time of over 73 months. CONCLUSIONS: A 250 mg dose of gefitinib offers good QoL and is safe for advanced NSCLC long-term survivors even after more than three years of treatment. According to the evaluation of the current tumor control statuses of patients, gefitinib demonstrates good efficacy in these active long-term survivors.

Safety and efficacy of first-line bevacizumab combined with taxane therapy in Chinese patients with HER2-negative locally recurrent or metastatic breast cancer: findings from the ATHENA study.

BACKGROUND: Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy. METHODS: In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients. RESULTS: Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature. CONCLUSIONS: We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.

High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal center subtype indicates limited survival benefit from R-CHOP therapy.

OBJECTIVES: Rituximab has significantly improved the survival of patients with DLBCL, especially those with non-germinal center B-cell-like (non-GCB) subtype. The impact of Ki-67 expression, an index of proliferation, on the clinical outcomes of patients with DLBCL has largely been unexplored. This study aimed to investigate whether Ki-67 expression is an indicator of outcome in DLBCL patients (especially non-GCB DLBCL patients) treated with standard chemotherapy combined with rituximab. METHODS: Expression of Ki-67 protein was examined immunohistochemically in 118 tumor specimens from patients newly diagnosed with DLBCL and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). RESULTS: Overall survival (OS) and progression-free survival (PFS) were lower in patients with high Ki-67 expression than in those with low Ki-67 expression (3-year OS: 65.2% vs. 81.7%, P = 0.030; 3-year PFS: 56.4% vs. 73.3%, P = 0.020), similar in patients with GCB subtype and those with the non-GCB subtype (OS: P = 0.330; PFS: P = 0.287). According to Ki-67 expression status by immunophenotype subgroups, patients with high Ki-67 expression in non-GCB subgroup had the most unfavorable PFS and OS, comparing with the other three subgroups (P = 0.004 and P = 0.002, respectively). In multivariate analysis, non-GCB with high Ki-67 expression was an independent prognostic predictor of inferior survival in DLBCL patients treated with R-CHOP. CONCLUSION: For DLBCL patients with non-GCB DLBCL and high Ki-67 expression, the survival benefit from R-CHOP therapy is limited.

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial.

BACKGROUND: The phase III Sorafenib Asia-Pacific (AP) trial-conducted in China, Taiwan and South Korea - confirmed that sorafenib improves overall survival (OS) and is safe for patients with advanced hepatocellular carcinoma (HCC). We performed a series of exploratory subset analyses to determine whether baseline status affected response to sorafenib. METHODS: In the Sorafenib AP trial, 226 patients with well-preserved liver function (>95% Child-Pugh A) were randomised 2:1 to sorafenib 400mg bid or matching placebo. Subanalyses were based on aetiology (hepatitis B virus present/absent); tumour burden (macroscopic vascular invasion and/or extrahepatic spread present/absent); presence or absence of either lung or lymph node metastasis at baseline, Eastern Cooperative Oncology Group performance status (0, 1-2); serum concentrations of alanine aminotransferase/aspartate aminotransferase (normal, mildly elevated, moderately elevated), alpha-fetoprotein (normal/elevated) and total bilirubin (normal/elevated); and whether or not there was a history of hepatectomy or transarterial chemoembolisation/embolisation. Subgroup assessments included OS, time to progression (TTP), disease control rate and safety. FINDINGS: Sorafenib consistently improved both median OS and median TTP, compared with placebo (range of hazard ratios (HR), 0.32-0.87 and 0.31-0.75, respectively). The most common grade 3/4 adverse events were hand-foot skin reaction, diarrhoea and fatigue, the incidence of which was similar between subgroups. INTERPRETATION: The efficacy and safety profiles of sorafenib in the subpopulations described were comparable with those in the overall study population. These exploratory analyses suggest that sorafenib is effective for patients from the AP region with advanced HCC, irrespective of baseline status.

[Chinese HER2 positive early breast cancer trastuzumab adjuvant therapy: preliminary outcomes].

OBJECTIVE: To evaluate the efficacy and safety of 1-year adjuvant trastuzumab (herceptin) versus 1-year non-trastuzumab observation in Chinese patients with HER2-positive early breast cancer during a median follow-up of 1 year. METHODS: The HERA trial was an international, multicenter, randomized, open-label, phase III trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard adjuvant chemotherapy, radiotherapy or both in patients with HER2-positive node-positive or high-risk node-negative early breast cancer. The primary endpoint was disease-free survival. Secondary end points included recurrence-free survival, distant disease-free survival, overall survival and cardiac safety. The first planned interim analysis comparing the efficacy and safety of treatment with trastuzumab for 1 year versus observation were completed in April 2005. Only the outcomes of recruited Chinese patients were reported. RESULTS: A total of 122 Chinese patients from 8 participating centers were included for planned interim analysis. And they were divided into trastuzumab (n = 68) and observation (n = 54) groups. Three and eight disease-free survival events were observed in the trastuzumab and observation groups respectively. Two-year disease-free survival rates were 92.9% and 81.4% respectively (P = 0.0489); 2-year recurrence-free survival and distant disease-free survivals were 98.1% vs 81.4% (P = 0.0064) and 98.1% vs 83.3% (P = 0.0117) respectively. Trastuzumab was generally well-tolerated with a decent safety profile. Severe cardiotoxicity was not observed. CONCLUSION: One-year treatment with adjuvant trastuzumab improves disease-free survival, recurrence-free survival and distant disease-free survival in Chinese patients with HER2-positive early breast cancer.

Clinical characteristics and prognostic factors in Chinese patients with Hodgkin's lymphoma.

The aim of our study is to investigate the clinical characteristics and prognostic factors in Chinese Hodgkin's lymphoma patients. It is known that clinical characteristics and epidemiology of Hodgkin's lymphoma in China are different from Western countries. In total, 137 consecutive, previously untreated patients with Hodgkin's lymphoma at Sun Yat-Sen University Cancer Center were enrolled. Among these patients, 92 were male and 45 were female, with a median age of 28 (range: 2-76) years. The bimodal age curve of classical Hodgkin's lymphoma analyzed from our patients was not obvious as the Western population, showing an early peak in 25 years and a second peak in 45 years. Most of the patients (41.6%) were classified as nodular sclerosis classic Hodgkin's lymphoma. Results showed that the 5-year overall survival, event-free survival, and disease-free survival rates were 97.7, 85.0, and 94.0%, respectively. Lymphopenia at diagnosis was related to poorer overall survival (P = 0.015) and event-free survival (P < 0.001) in all-stage Hodgkin's lymphoma patients. Multivariate analysis showed that lymphopenia as an independent unfavorable prognostic factor influenced event-free survival (P = 0.015). The international prognostic score ≥ 5 was also the only independent prognostic factor of disease-free survival in advanced-stage patients (P = 0.046). Our findings demonstrated that some clinical characteristics of Hodgkin's lymphoma in China were different from those in the Western countries. Lymphopenia was an effective prognostic predictor in both early stage and advanced stage.