Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer:a subpopulation analysis of the JACOB trial

Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results presented here are descriptive only and need to be interpreted with caution.Conclusions:OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients,and this regimen demonstrated an acceptable safety profile.

Safety and efficacy of obinutuzumab in Chinese patients with B-cell lymphomas: a secondary analysis of the GERSHWIN trial

Background:Patients with relapsed/refractory B-cell lymphomas have limited treatment options.GERSHWIN is an open-label,single-arm,phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically docu-mented CD20+relapsed/refractory chronic lymphocytic leukemia(CLL),diffuse large B-cell lymphoma(DLBCL),or follicular lymphoma(FL).The primary outcome measure of pharmacokinetics has been previously reported.We now present data on the secondary endpoint measures(e.g.,safety,and efficacy and pharmacodynamics).Methods:Patients received 1000 mg obinutuzumab intravenously on days 1,8,and 15 of cycle 1(CLL patients;first dose split over 2 days),and on day 1 of cycles 2-8.Each cycle lasted for 21 days;the treatment period was 24 weeks.All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety,efficacy,as well as pharmacodynamics.Results:A total of 48 patients(>18 years of age)were enrolled(CLL:12;DLBCL:23;FL:13).The subjects received a median of two lines of anticancer treatment prior to the enrollment.Thirty-five patients(72.9%)had at least one adverse event(AE).The most frequent AE was infusion-related reactions(15 patients;31.3%),followed by pyrexia(11 patients;22.9%).Treatment-related AEs were reported in 28 patients(58.3%),and included one death(interstitial lung disease).End-of-treatment(EoT)response rate was 33.3%.Best overall response rate was 47.9%.Most CLL patients achieved a partial response at EoT(58.3%).CD19+depletion occurred in 75.0%of the patients with CLL,and all patients with FL and DLBCL.Conclusions:The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients;no new safety signals were observed.