Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer:efficacy,safety,and biomarker results from Chinese patients

Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC.The primary endpoint was clinical benefit rate(CBR).Secondary endpoints included progression-free survival(PFS),time to response(TTR),duration of response(DoR),central nervous system(CNS) as first site of relapse,and safety.The results showed that there were 23 patients with partial responses and 7 patients with stable disease,resulting in a CBR of 57.7%.The median PFS was 6.34 months(95% confidence interval,4.93-9.82 months).The median TTR and DoR were 4.07 months(range,0.03-14.78 months) and 6.93 months(range,1.45-9.72 months),respectively.Thirteen(25.0%) patients had new lesions as disease progression.Among them,2(3.8%) patients had CNS disease reported as the first relapse.The most common toxicities were palmar-plantar erythrodysesthesia(59.6%),diarrhea(48.1%),rash(48.1%),hyperbilirubinemia(34.6%),and fatigue(30.8%).Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample,baseline PIK3CA mutation status was not associated with CBR(P = 0.639) or PFS(P = 0.989).These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC,irrespective of PIK3CA status.

Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

AIM: To determine whether the positive status of human epidermal growth receptor 2(HER2) can be regarded as an effective prognostic factor for patients with gastric cancer(GC) undergoing R0 resection.METHODS: A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical(IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-nodemetastasis(TNM) stage, with additional adjustment for potential prognostic factors.RESULTS: Among 1562 patients, 548(positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender(P = 0.004), minority(P < 0.001), tumor location(P = 0.001), pathological grade(P < 0.001), TNM stage(P < 0.001) and adjuvant radiotherapy(74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival(HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival(HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages(Ⅰ and Ⅱ). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION: The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.

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.

Impact of coronavirus disease 2019 on the clinical diagnosis and treatment of breast cancer in China

To the Editor:Since December 2019,the epidemic of coronavirus disease 2019(COVID-19)has become the focus of attention in China and worldwide.Despite the effective control of the outbreak in China,the global situation of COVID-19 was not optimistic which has gradually become a global threat of the year 2020.COVID-19 may cause high mortality in the elderly and patients with cardiovascular diseases,malignant tumors,and other underlying diseases.