Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer:a multicenter,open-label,non-inferiority,randomized controlled trial

Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Efficacy of moxifloxacin-based sequential therapy for first-line eradication of Helicobacter pylori infection in gastrointestinal disease

AIM:To evaluate the efficacy of 14-d moxifloxacinbased sequential therapy as first-line eradication treatment of Helicobacter pylori(H.pylori) infection.METHODS:From December 2013 to August 2014, 161 patients with confirmed H.pylori infection randomly received 14 d of moxifloxacin-based sequential group(MOX-ST group, n = 80) or clarithromycin-based sequential group(CLA-ST group, n = 81) therapy.H.pylori infection was defined on the basis of at least one of the following three tests:a positive 13C-urea breath test; histologic evidence of H.pylori by modified Giemsa staining; or a positive rapid urease test(CLOtest; Delta West, Bentley, Australia) by gastric mucosal biopsy.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test four weeks after the end of eradication treatment.Compliance was defined as good when drug intake was at least 85%.H.pylori eradication rates, patient compliance with drug treatment, adverse event rates, and factors influencing the efficacy of eradication therapy were evaluated.RESULTS:The eradication rates by intention-to-treat analysis were 91.3%(73/80;95%CI:86.2%-95.4%)in the MOX-ST group and 71.6%(58/81;95%CI:65.8%-77.4%)in the CLA-ST group(P=0.014).The eradication rates by per-protocol analysis were 93.6%(73/78;95%CI:89.1%-98.1%)in the MOX-ST group and 75.3%(58/77;95%CI:69.4%-81.8%)in the CLAST group(P=0.022).Compliance was 100%in both groups.The adverse event rates were 12.8%(10/78)and 24.6%(19/77)in the MOX-ST and CLA-ST group,respectively(P=0.038).Most of the adverse events were mild-to-moderate in intensity;there was none serious enough to cause discontinuation of treatmentin either group.In multivariate analysis,advanced age(≥60 years)was a significant independent factor related to the eradication failure in the CLA-ST group(adjusted OR=2.13,95%CI:1.97-2.29,P=0.004),whereas there was no significance in the MOX-ST group.CONCLUSION:The 14-d moxifloxacin-based sequential therapy is effective.Moreover,it shows excellent patient compliance and safety compared to the 14-d clarithromycin-based sequential therapy.

Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication:A randomized study in Japan

AIM:To find the way to improve the eradication rate of first-line therapy in Japanese patients.METHODS:We prospectively compared the effectiveness of 7-d quadruple therapy to standard 7 d triple therapy in Japanese patients infected with Helicobacter pylori(H.pylori).One hundred and nineteen patients were randomly assigned to receive 7-d non-bismuth quadruple therapy with lansoprazole,amoxicillin,clarithromycin and metronidazole(LACM7) or 7-d triple therapy with lansoprazole,amoxicillin and clarithromycin(LAC7).After three months,H.pylori status was analyzed by 13C-urea breath test.Incidence rates of adverse events were evaluated by use of questionnaires.RESULTS:By intention-to-treat(ITT) analysis,the eradication rate in the LACM7 group was 94.9%,which was significantly higher than the LAC7 group(68.3%,P < 0.001).Per protocol analysis also showed a significantly higher eradication rate in the LACM7 group(98.3%) than the LAC7 group(73.2%,P < 0.001).Nevertheless,the incidence of serious adverse events did not differ between the two groups(RR:1.10,95% CI:0.70-1.73,P = 0.67).CONCLUSION:Seven day non-bismuth quadruple therapy(LACM7) was superior to standard 7-d triple therapy(LAC7) for first-line eradication.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

Two-week bismuth-containing quadruple therapy and concomitant therapy are effective first-line treatments for Helicobacter pylori eradication: A prospective open-label randomized trial

BACKGROUND Increasing levels of antibiotic resistance have reduced the Helicobacter pylori(H.pylori)eradication rates afforded by the standard triple therapy.Thus,2-wk firstline four-drug regimens must be considered.AIM To analyze the eradication rates of modified bismuth-containing quadruple therapy(mBCQT)and concomitant therapy(CT),the associated adverse events,and compliance.METHODS Patients infected with H.pylori were prospectively randomized to receive mBCQT or CT for 2 wk.mBCQT featured a proton pump inhibitor(PPI),bismuth,metronidazole,and tetracycline,taken twice daily.CT included a PPI,clarithromycin,metronidazole,and amoxicillin,taken twice daily.The 13C-urea breath test was performed no earlier than 4 wk after therapy concluded to confirm eradication.If either the histological or rapid urease test was positive,H.pylori infection was diagnosed.RESULTS The demographic characteristics of 68 patients who received mBCQT and 68 who received CT did not differ significantly.On intention-to-treat analysis,the eradication rate was 88.2%(60/68)in the mBCQT group and 79.4%(54/68)in the CT group(P=0.162).By per-protocol analysis,the respective eradication rates were 98.4%(60/61)and 93.1%(54/58)(P=0.199).More CT than mBCQT patients experienced adverse events[33.8%(23/68)mBCQT vs 51.5%(35/58)CT patients,respectively,P=0.037].All patients showed good compliance[85.3%(58/68)mBCQT vs 82.4%(56/68)CT patients,P=0.641].CONCLUSION The H.pylori eradication rates of the 2-wk mBCQT and CT regimens are high.Most patients show good compliance,and more CT than mBCQT patients experience adverse events.

Efficacy of moxifloxacin-based sequential and hybrid therapy for first-line Helicobacter pylori eradication

AIM: To evaluate the efficacy of moxifloxacin-based sequential therapy(MBST) versus hybrid therapy as a first-line treatment for Helicobacter pylori(H. pylori) infection.METHODS: From August 2014 to January 2015, 284 patients with confirmed H. pylori infection were randomized to receive a 14-d course of MBST(MBST group, n = 140) or hybrid(Hybrid group, n = 144) therapy. The MBST group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 7 d, followed by 20 mg rabeprazole and 500 mg metronidazole twice daily, and 400 mg moxifloxacin once daily for 7 d. The Hybrid group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 14 d. In addition, the Hybrid group received 500 mg metronidazole and 500 mg clarithromycin twice daily for the final 7 d. Successful eradication of H. pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of treatment. Patient compliance was defined as "good" if drug intake was at least 85%. H. pylori eradication rates, patient compliance with treatment, and adverse event rates were evaluated.RESULTS: The eradication rates in the intention-totreat(ITT) analysis were 91.4%(128/140; 95%CI: 90.2%-92.9%) in the MBST group and 79.2%(114/144; 95%CI: 77.3%-80.7%) in the Hybrid group(P = 0.013). The eradication rates in the perprotocol(PP) analysis were 94.1%(128/136; 95%CI: 92.9%-95.6%) in the MBST group and 82.6%(114/138; 95%CI: 80.6%-84.1%) in the Hybrid group(P = 0.003). The H. pylori eradication rate in the MBST group was significantly higher than that of the Hybrid group for both the ITT(P = 0.013) and the PP analyses(P = 0.003). Both groups exhibited full compliance with treatment(MBST/Hybrid group: 100%/100%). The rate of adverse events was 11.8%(16/136) and 19.6%(27/138) in the MBST and Hybrid group, respectively(P = 0.019). The majority of adverse events were mild-to-moderate in intensity; none were severe enough to cause discontinuation of treatment in either group.CONCLUSION: MBST was more effective and led to fewer adverse events than hybrid therapy as a first-line treatment for H. pylori infection.

Quadruple therapy with moxifloxacin and bismuth for first-line treatment ofHelicobacter pylori

AIM:To compare triple therapy vs quadruple therapy for 10 d as first-line treatment ofHelicobacter pylori(H.pylori) infection.METHODS:Consecutive H.pylori positive patients never treated in the past for this infection were randomly treated with triple therapy of pantoprazole(PAN) 20 mg bid,amoxicillin(AMO) 1 g bid and moxifloxacin(MOX) 400 mg bid for 10 d(PAM) or with quadruple therapy of PAN 20 mg bid,AMO 1 g bid,MOX 400 mg bid and bismuth subcitrate 240 mg bid for 10 d(PAMB).All patients were found positive at 13 C-Urea breath test(UBT) performed within ten days prior to the start of the study.A successful outcome was confirmed with an UBT performed 8 wk after the end of treatment.χ 2 analysis was used for statistical comparison.Per protocol(PP) and intention-to-treat(ITT) values were also calculated.RESULTS:Fifty-seven patients were enrolled in the PAM group and 50 in the PAMB group.One patient in each group did not return for further assessment.Eradication was higher in the PAMB group(negative:46 and positive:3) vs the PAM group(negative:44 and positive:12).The H.pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group,both with the PP and ITT analyses(PP:PAMB 93.8%,PAM 78.5%,P < 0.02;ITT:PAMB 92%,PAM 77.1 %,P <0.03).CONCLUSION:The addition of bismuth subcitrate can be considered a valuable adjuvant to triple therapy in those areas where H.pylori shows a high resistance to fluoroquinolones.

Capecitabine Maintenance Therapy after First-Line Chemotherapy in Patients with Metastatic Colorectal Cancer

Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC) patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from first-line chemotherapy,patients with mCRC in our hospital received two different treatment strategies.Thirty-three patients in maintenance group were treated with capecitabine 1000 mg/m2 po bid d1-14,q21d.Fifty-two patients in non-maintenance group did not receive any further chemotherapy.Results:Patients in maintenance group and non-maintenance group both received FOLFOX,FOLFIRI and XELOX as first-line therapy.The median chemotherapy cycles the two groups received were the same(6 vs 6).The response rates of first-line chemotherapy were 33.3% in maintenance group and 32.7% in non-maintenance group.Patients in maintenance group received 3-9 cycles of capecitabine therapy(median cycle 4).29/33(87.9%) patients in maintenance group and 47/52(90.4%) in non-maintenance group received following second-line chemotherapy,and no patients underwent targeted therapy.The median survival time and TTP were 40.4 months(95%CI:24.2-56.6) and 9.0 months(95%CI:6.7-11.3) in maintenance group,as compared with 21.5 months(95%CI:14.9-28.0,P=0.015) and 6.5 months(95%CI:4.4-8.5,P=0.007) in non-maintenance group.No severe adverse event was observed in the capecitabine maintenance group.Conclusion:mCRC patients could benefit from capecitabine maintenance therapy by prolonging survival time and TTP.

A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective： To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer （NSCLC） patients who obtained disease control （DC） after first-line chemotherapy in Chinese population. Methods： Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time （OS）, the second end point was disease control rate （DCR） and progression-free survival time （PFS）. DCR included complete response （CR） plus partial response （PR） and plus stable disease （SD）. The impact of epidermal growth factor receptor （EGFR） mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography （DHPLC）. Results： Among 75 enrolled patients, the overall response rate was 37% and the DCR （CR ＋ PR ＋SD） was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type （25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively）. In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS （P=0.029 and 0.017, respectively）, however, rash status was the predictor in terms of PFS （P=0.027）. Conclusion： Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.

Selection of first-line systemic therapies for advanced hepatocellular carcinoma:A network meta-analysis of randomized controlled trials

BACKGROUND The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma(HCC)used placebo or sorafenib as comparators,and there are limited data providing a cross comparison of treatments in this setting,especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments.AIM To systematically review and compare response rates,survival outcomes,and safety of first-line systemic therapies for advanced hepatocellular carcinoma.METHODS We searched PubMed,Science Direct,the Cochrane Database,Excerpta Medica Database,and abstracts from the American Society of Clinical Oncology 2020 annual congress.Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC.Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials.A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments.P value,a frequentist analog to the surface under the cumulative ranking curve,was used to rank treatments.RESULTS In total,1398 articles were screened and 27 included.Treatments compared were atezolizumab plus bevacizumab,brivanib,donafenib,dovitinib,FOLFOX4,lenvatinib,linifanib,nintedanib,nivolumab,sorafenib,sunitinib,vandetanib,11 sorafenib combination therapies,and three other combination therapies.For overall response rate,lenvatinib ranked 1/19,followed by atezolizumab plus bevacizumab and nivolumab.For progression-free survival(PFS),atezolizumab+bevacizumab was ranked 1/15,followed by lenvatinib.With the exception of atezolizumab+bevacizumab[hazard ratios(HR)PFS=0.90;95%confidence interval(CI):0.64-1.25],the estimated HRs for PFS for all included treatments vs lenvatinib were>1;however,the associated 95%CI passed through unity for bevacizumab plus erlotinib,linifanib,and FOLFOX4.For overall survival,atezolizumab plus bevacizumab was ranked 1/25,followed by vandetanib 100 mg/d and donafinib,with lenvatinib ranked 6/25.Atezolizumab+bevacizumab was associated with a lower risk of death vs lenvatinib(HRos=0.63;95%CI:0.44-0.89),while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity.Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13,respectively,for the lowest incidence of treatment terminations due to adverse events,followed by sorafenib(5/13),lenvatinib(10/13),and atezolizumab+bevacizumab(13/13).CONCLUSION There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements.Therefore,first-line systemic treatment should be selected based on individualized treatment goals.

Noninvasive molecular analysis of Helicobacter pylori : Is it time for tailored first-line therapy?

The main problem of Helicobacter pylori(H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction(PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.

Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung Cancer

Objective： To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment （immediate group） vs. those received delayed treatment upon disease progression as second-line therapy （delayed group）. Methods： The study included 159 no-small-cell lung cancer （NSCLC） patients who received gefitinib or erlotinib as maintenance treatment in the immediate group （85 patients） or as second-line therapy in the delayed group （74 patients）. The primary end point was progression-free survival （PFS）. EGFR mutation status was detected using denaturing high-performance liquid chromatography （DHPLC）. Results： PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively （hazard ratio [HR], 0.99; 95% Confidence Interval [CI]： 0.69-1.42; P=0.947）. In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group （HR, 0.48; 95% CI： 0.27-0.85; P=0.012）. In patients with wild type EGFR, the risk for disease progression was comparable between the two groups （HR, 1.23; 95% CI： 0.61-2.51; P=0.564）. No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival （OS） （26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI： 0.27 to 1.06; P=0.072）. There was also no difference in the incidence of adverse events between the two groups. Conclusions： EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Injectable versus oral first-line multiple sclerosis therapies:knows and unknowns from observational studies

The approval of oral disease modifying therapies(DMTs) for relapsing-remitting multiple sclerosis(RRMS) has changed considerably the therapeutic scenario and they often represent the first therapeutic choice for patients with RRMS,since their safety and efficacy profile has been extensively validated(D'Amico et al.,2015).

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

Research Progress of Radical Treatment of Helicobacter Pylori Based on Drug Sensitivity Test as First-Line Treatment

Helicobacter pylori (HP) infection is a global problem that affects about half of the world’s population and requires sufficient attention in clinical and scientific work. Due to differences in economic and medical conditions among countries around the world, there is currently no unified treatment plan for anti-HP. In China, empirical quadruple therapy is mainly used. With the abuse of antibiotics, many patients face the problem of secondary eradication after failure, and the resistance rate of HP is gradually increasing. After eradication failure, drug sensitivity cultivation is carried out to choose sensitive antibiotics for treatment. A new strategy is currently needed to address how to improve the eradication rate of HP during the first eradication. This article aims to discuss the first-line treatment plans and research progress for eradicating HP based on drug sensitivity testing before eradication. Compared with traditional empirical therapies, treatment based on drug sensitivity results can effectively improve the eradication rate of HP, and reduce drug resistance rates, and adverse reactions, among other benefits. .

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

Comparative effectiveness of first-line therapies for eradication of antibiotic-resistant Helicobacter pylori strains:A network metaanalysis

BACKGROUND As a first-line treatment regimen for Helicobacter pylori(H.pylori)infection,antibiotic therapy is widely used worldwide.However,the question of increasing antibiotic resistance must be considered.Given this issue,we need to find ways to reduce drug resistance.This study examined all currently available first-line regimens and compared them with standard triple treatment through a network meta-analysis of randomized controlled trials(RCTs).AIM To compare first-line treatment regimens for eradication of antibiotic-resistant H.pylori strains.METHODS To compare the effectiveness of the first-line regimens for treating H.pylori infection,a Bayesian network meta-analysis was applied to process data extracted from RCTs.The plausible ranking for each regimen was assessed by the surface under the cumulative ranking curve(SUCRA).In addition,we conducted a relevant search by reference citation analysis.RESULTS Twenty-five RCTs involving 12029 participants[including 1602 infected with clarithromycin(CAM)-resistant strains and 1716 infected with metronidazole(MNZ)-resistant strains]were included,in which a total of seven regimens were used for H.pylori eradication.The results showed that dual therapy containing a high-dose proton pump inhibitor(HDDT)[odds ratio(OR):4.20,95%confidence interval(CI):2.29-8.13]was superior to other therapies for all patients,including those with CAM/MNZ-resistant H.pylori infection.In the comparative effectiveness ranking,for CAM-resistant H.pylori,HDDT(OR:96.80,95%CI:22.46-521.9)had the best results,whereas standard triple therapy ranked last(SUCRA:98.7%vs 0.3%).In the subgroup of high cure rates(≥90%),HDDT was also generally better than other therapies.CONCLUSION For the eradication of CAM-and MNZ-resistant H.pylori strains,HDDT exhibited considerable advantages.The studies of CAM-resistant H.pylori were based on small samples due to a lack of antibiotic sensitivity tests in many RCTs,but the results showed that all patients,including those with CAM-resistant H.pylori infection,had a concordant trend.Overall,HDDT may be a reference for RCTs and other studies of H.pylori eradication.