Qingyuan Zhang

Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1) : a phase 3, randomised, double-blind, multicentre trial

BACKGROUND mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due to PTEN loss, by sensitising PTEN-deficient tumours to trastuzumab. The BOLERO-1 study assessed the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer. METHODS In this phase 3, randomised, double-blind trial, patients were enrolled across 141 sites in 28 countries. Eligible patients were aged 18 years or older, with locally assessed HER2-positive advanced breast cancer, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, who had not received previous trastuzumab or chemotherapy for advanced breast cancer within 12 months of randomisation, had measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) or bone lesions in the absence of measurable disease, without previous systemic treatment for advanced disease except endocrine therapy. Patients were randomly assigned (2:1) with an interactive voice and web response system to receive either 10 mg everolimus once a day orally or placebo plus weekly trastuzumab intravenously at 4 mg/kg loading dose on day 1 with subsequent weekly doses of 2 mg/kg of each 4 week cycle plus paclitaxel intravenously at a dose of 80 mg/m(2) on days 1, 8, and 15 of each 4 week cycle. Randomisation was stratified according to previous use of trastuzumab and visceral metastasis. Patients and investigators were masked to the assigned treatments. Identity of experimental treatments was concealed by use of everolimus and placebo that were identical in packaging, labelling, appearance, and administration schedule. The two primary objectives were investigator-assessed progression-free survival in the full study population and in the subset of patients with hormone receptor-negative breast cancer at baseline; the latter was added during the course of the study, before unmasking based on new clinical and biological findings from other studies. All efficacy analyses were based on the intention-to-treat population. Enrolment for this trial is closed and results of the final progression-free survival analyses are presented here. This trial is registered with ClinicalTrials.gov, number NCT00876395. FINDINGS Between Sept 10, 2009, and Dec 16, 2012, 719 patients were randomly assigned to receive everolimus (n=480) or placebo (n=239). Median follow-up was 41·3 months (IQR 35·4-46·6). In the full population, median progression-free survival was 14·95 months (95% CI 14·55-17·91) with everolimus versus 14·49 months (12·29-17·08) with placebo (hazard ratio 0·89, 95% CI 0·73-1·08; p=0·1166). In the HR-negative subpopulation (n=311), median progression-free survival with everolimus was 20·27 months (95% CI 14·95-24·08) versus 13·08 months (10·05-16·56) with placebo (hazard ratio 0·66, 95% CI 0·48-0·91; p=0·0049); however, the protocol-specified significance threshold (p=0·0044) was not crossed. The most common adverse events with everolimus were stomatitis (314 [67%] of 472 patients in the everolimus group vs 77 [32%] of 238 patients in the placebo group), diarrhoea (267 [57%] vs 111 [47%] patients), and alopecia (221 [47%] vs 125 [53%]). The most frequently reported grade 3 or 4 adverse events in the everolimus group versus the placebo group were neutropenia (117 [25%] vs 35 [15%]), stomatitis (59 [13%] vs three [1%]), anaemia (46 [10%] vs six [3%]) and diarrhoea (43 [9%] vs 10 [4%]) On-treatment adverse event-related deaths were reported in 17 (4%) patients in the everolimus group and none in the placebo group. INTERPRETATION Although progression-free survival was not significantly different between groups in the full analysis population, the 7·2 months prolongation we noted with the addition of everolimus in the HR-negative, HER2-positive population warrants further investigation, even if it did not meet prespecified criteria for significance. The safety profile was generally consistent with what was previously reported in BOLERO-3. Proactive monitoring and early management of adverse events in patients given everolimus and chemotherapy is crucial. FUNDING Novartis Pharmaceuticals.

Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial

BACKGROUND Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. METHODS We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m(2) per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. FINDINGS Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95% CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). INTERPRETATION Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. FUNDING Boehringer Ingelheim.

Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracyclines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial

BACKGROUND Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer. METHODS We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens. We randomly assigned participants (2:1) using computer based randomisation and block sizes of 6 to a 21-day cycle of either utidelone (30 mg/m2 intravenously once per day on days 1-5) plus capecitabine (1000 mg/m2 orally twice per day on days 1-14), or capecitabine alone (1250 mg/m2 orally twice per day on days 1-14), until disease progression or unacceptable toxicity occurred. Patients, physicians, and assessors were not masked to treatment allocation; however, an independent radiology review committee used to additionally assess response was masked to allocation. The primary endpoint was centrally assessed (by an independent radiology review committee) progression-free survival, and analysed using the Kaplan-Meier product-limit method in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. Follow-up is ongoing. This study is registered at ClinicalTrials.gov, number NCT02253459. FINDINGS Between Aug 8, 2014, and Dec 14, 2015, we enrolled and randomly assigned 270 patients to treatment with utidelone plus capecitabine, and 135 to capecitabine alone. Median follow-up for progression-free survival was 6·77 months (IQR 3·81-10·32) for the utidelone plus capecitabine group and 4·55 months (2·55-9·39) for the capecitabine alone group. Median progression-free survival by central review in the utidelone plus capecitabine group was 8·44 months (95% CI 7·95-9·92) compared with 4·27 months (3·22-5·68) in the capecitabine alone group; hazard ratio 0·46, 95% CI 0·36-0·59; p<0·0001. Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group (58 [22%] of 267 patients vs 1 [<1%] of 130 patients in the capecitabine alone group). Palmar-plantar erythrodysaesthesia was the most prominent grade 3 adverse event in the capacitabine alone group (in 10 [8%] of 130 patients) and was the next most frequent grade 3 event in the utidelone plus capecitabine group (in 18 [7%] of 267 patients). 16 serious adverse events were reported in the combination therapy group (diarrhoea was the most common, in three [1%] patients) and 14 serious adverse events were reported in the monotherapy group (the most common were diarrhoea, increased blood bilirubin, and anaemia, in two [2%] patients for each event). 155 patients died (99 in the combination therapy arm, 56 in the monotherapy arm). All deaths were related to disease progression except for one in each group (attributed to pericardial effusion in the combination therapy group and dyspnoea in the monotherapy group) that were considered possibly or probably treatment-related. INTERPRETATION Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer. FUNDING Beijing Biostar Technologies, Beijing, China.

Abstract P5-19-01: Randomized Phase III trial of afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one prior trastuzumab treatment: LUX-Breast 1

Background: Afatinib is an oral, irreversible ErbB family blocker with anti-tumour activity in patients (pts) with HER2-positive metastatic breast cancer (MBC) after failure on trastuzumab.1 Preclinically, afatinib + vinorelbine (AV) showed an additive effect; clinically, the AV combination had a manageable safety profile and showed activity in two Phase I trials.2,3 This randomized, open-label, Phase III trial (LUX-Breast 1) compared AV with trastuzumab + vinorelbine (TV) in pts with HER2-positive MBC who had progressed on a prior T-based regimen. Methods: Pts with HER2-positive MBC and failure of one T-based regimen (adjuvant/first-line) were randomized 2:1 to AV (40 mg/day oral + 25 mg/m2/week iv) or TV (2 mg/kg/week iv after 4 mg/kg loading dose + 25 mg/m2/week iv). Treatment continued until progressive disease (PD) or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS) by investigator review; secondary endpoints included objective response rate (ORR), overall survival (OS) and safety. Planned accrual was 780 pts. Results Between August 2010 and April 2013, 508 patients were randomized (AV:339, TV:169). Baseline characteristics were balanced in both arms (mean age 52 yrs, Asian 50.6%, White 41.6%, ER/PR positive 28.7%). 41.1% of pts failed on prior adjuvant and 58.9% on 1st line T-based treatment. A pre-planned risk/benefit assessment was found unfavorable by the DMC and recruitment was stopped. Pts ongoing on AV therapy were switched to TV, received A or V monotherapy, or stopped treatment. Primary endpoint analysis was performed with 307 of the originally 484 planned PFS events (211 [62.2%] AV arm; 96 [56.8%] TV arm). Median PFS was 5.5 months with AV vs 5.6 months with TV (HR 1.10; 95% CI 0.86, 1.41; P=0.4272). ORR was 46.1% with AV and 47.0% with TV (OR 1.04; 95% CI 0.71, 1.51; P=0.8510). OS analysis was based on 144 (28.4%) OS events (108 [31.9%] in AV arm; 36 [21.3%] in TV arm). Median OS was 19.6 months with AV and 28.6 months with TV (HR 1.76; 95% CI 1.20, 2.59; P=0.0036). The most common drug-related AEs were diarrhea (80.1%), neutropenia (75.1%) and rash (45.1%) with AV, and neutropenia (78.7%), leukopenia (37.3%) and anemia (27.8%) with TV. Rate of infections (53.0% vs 40.5%) was higher with AV vs TV. More AV than TV pts discontinued due to AEs (15.4% vs 7.1%). Fatal AEs were reported for 18 (5.3%) in the AV vs 5 (3.0%) pts in the TV arm, and were mainly associated with PD (9 pts in AV and 1 in TV arm). Three AV pts died due to treatment-related causes (sepsis/multi-organ failure; septic shock; pulmonary fibrosis). Conclusions: AV and TV demonstrated similar PFS and ORR, but OS diverged and was shorter for AV compared to TV in pts with HER2-positive MBC. The safety profile of AV was consistent with the individual monotherapies, but its tolerability compared unfavorably to TV. Analyses are ongoing to elucidate potential factors (e.g. impact of follow up treatments) contributing to the diverging PFS and OS outcomes. 1. Lin NU et al. Breast Cancer Res Treat 2012;133:1057-65 2. Bahleda R et al. J Clin Oncol 2011;29; abs 2585 3. Masuda N et al. SABCS 2013 abs P4-16-11. Citation Format: Nadia Harbeck, Chiun-Sheng Huang, Sara Hurvitz, Dah-Cherng Yeh, Zhimin Shao, Seock-Ah Im, Kyung Hae Jung, Kunwei Shen, Jungsil Ro, Jacek Jassem, Qingyuan Zhang, Young-Hyuck Im, Marek Wojtukiewicz, Qiang Sun, Shin-Cheh Chen, Rainer-Georg Goeldner, Annick Lahogue, Martina Uttenreuther-Fischer, Binghe Xu, Martine Piccart-Gebhart, on Behalf of the LUX-Breast 1 Study Group. Randomized Phase III trial of afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one prior trastuzumab treatment: LUX-Breast 1 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-01.

Fulvestrant 500 mg vs 250 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer: a randomized, double-blind registrational trial in China

The international CONFIRM study showed that fulvestrant 500 mg improved progression-free survival (PFS) vs fulvestrant 250 mg in postmenopausal women with estrogen receptor (ER)-positive locally advanced/metastatic breast cancer (LA/MBC). In this randomized, double-blind study, postmenopausal Chinese women with ER-positive LA/MBC and progression after endocrine therapy received fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or fulvestrant 250 mg (every 28 days). Consistency with the international study was assumed if the hazard ratio (HR) for comparison of PFS (primary endpoint) was < 1 (stratified log-rank test). The study was not powered to assess between-group differences. In total, 221 patients were randomized (fulvestrant 500 mg: n = 111; fulvestrant 250 mg: n = 110). Baseline characteristics were balanced. Median PFS was 8.0 months with fulvestrant 500 mg vs 4.0 months with 250 mg (HR = 0.75; 95% confidence interval [CI] 0.54−1.03; P = 0.078). PFS (HR; 95% CI) favored fulvestrant 500 mg in post-antiestrogen (0.86; 0.54−1.37) and post-aromatase inhibitor (0.65; 0.42−1.03) settings. No new safety considerations were observed. These results are consistent with the international CONFIRM study, supporting the superior clinical benefit of fulvestrant 500 mg in women with ER-positive LA/MBC experiencing progression following prior endocrine therapy.

National consensus in China on diagnosis and treatment of patients with advanced breast cancer

The recently available guidelines on the management of advanced breast cancer (ABC) organized by Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) do not elucidate ABC in details. To instruct clinicians in treatment of ABC, a Chinese expert consensus meeting on diagnosis and treatment of ABC was held in June 2014 and a consensus is developed. The following consensus provides the level of evidence and supporting documents for each recommendation, and introduces research topics to be urgently addressed. Notably, the consensus on diagnosis and treatment of ABC in China is developed to be applied nationwide. In different areas, multidisciplinary treatment (MDT) tailored to the each patient and the disease itself should be applied based on the basic principles of modern oncology.

The Krüppel-Like Factor 6 Genotype is Associated with Gastric Cancer in a Chinese Population

Association of the IVS1 −27G/A polymorphism of Krüppel-like factor 6 (KLF6) with gastric cancer was examined in a Chinese population comprising 300 gastric cancer patients and 300 healthy controls. Single-nucleotide polymorphism analysis was performed by amplifying intron 1 of KLF6 and sequencing the products. The KLF6 genotype IVS1 −27AA was significantly less frequent in gastric cancer patients than in controls and significantly less frequent in patients with advanced (stage III/IV) gastric cancer than in those with early (stage I/II) cancer. Stratification by location, Laurens classification and histological differentiation revealed no significant differences in genotype distribution. Thus, in this Chinese population the KLF6 IVS1 −27AA genotype was associated with a decreased risk of gastric cancer and with cancer stage. Further study is required to clarify the mechanisms involved and, potentially, to facilitate the design of effective clinical trials.

Recombinant humanised anti-PD-1 monoclonal antibody (JS001) treatment for patients with refractory or metastatic nasopharyngeal carcinoma: preliminary results of an open-label, phase 1b/2, clinical study

Abstract Background Patients with unresectable or recurrent nasopharyngeal cancer who have disease progression after standard therapy have few treatment options and represent an important, unmet medical need. Nasopharyngeal cancer is closely associated with Epstein-Barr virus (EBV) infection and has been reported to have high concentrations of PD-L1 expression and tumour-infiltrating lymphocytes, which indicate a potential implication of PD-1 blockade in the treatment of nasopharyngeal cancer. JS001, a humanised recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1, with its ligands PD-L1 and PD-L2, and promotes antigen-specific T-cell activation. Results of a phase 1 study of JS001 treatment in Chinese patients with heavily pretreated solid tumours have shown an acceptable safety profile in doses up to 10 mg/kg once every 2 weeks until progressive disease, intolerance, withdrawal of consent, or investigator decision. Here we report the safety and efficacy of JS001 in a phase 1b/2 clinical study. Methods We did this open-label, phase 1b/2, clinical study in Chinese patients with refractory or metastatic nasopharyngeal cancer received JS001 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks according to the immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) criteria. Tumour PD-L1 expression, plasma EBV DNA concentration, and additional potential predictive biomarkers were monitored for correlation with clinical response. This study is registered with ClinicalTrials, number NCT02915432. Findings Between Dec 29, 2016, and June 19, 2017, we enrolled 48 patients with nasopharyngeal cancer. Of 23 evaluable patients, the median age was 46 years (range 33–70), 81% were male, and EBV serology tested positive in 92%. Adverse events occurred in 46 (96%) of 48 patients, which were mostly grade 1 or 2. Grade 3 and worse adverse events occurred in 17 patients (35%), including abnormal liver function (n=6, 13%), dysphagia (n=2, 4%), and pulmonary infection (n=2, 4%). Rapid and deep clinical responses were observed. Seven patients (15%) had partial responses while ten patients (21%) achieved stable disease, with the proportion of patients who achieved an objective response of 30% and a disease control of 73%. The responses seemed unrelated to PD-L1 expression status on tumour biopsy. Interpretation JS001 treatment has shown good clinical activity in heavily pretreated patients with nasopharyngeal cancer and a manageable safety profile. We plan to enrol 54 patients with nasopharyngeal cancer to further monitor the safety and efficacy of JS001 treatment. Funding Shanghai Science and Technology Innovation Fund.

Palbociclib plus letrozole as first-line treatment for ER-positive and HER2-negative advanced breast cancer in Chinese women: a phase 1 study

Abstract Background Palbociclib, a cyclin-dependent kinase 4 and 6 inhibitor, is approved in many countries for the treatment of ER-positive and HER2-negative advanced breast cancer in combination with endocrine therapy. We aimed to evaluate the pharmacokinetics, safety, and efficacy of palbociclib combined with letrozole as first-line treatment for ER-positive and HER2-negative advanced breast cancer. Methods This is a phase 1, open-label, single-arm study in Chinese women with ER-positive and HER2-negative advanced breast cancer. From cycle 1 day 1, patients received letrozole 2·5 mg orally once daily continuously plus palbociclib 125 mg orally once daily for 3 weeks followed by 1 week off treatment. Blood samples for pharmacokinetic evaluation of palbociclib were collected up to 120 h after a single dose of palbociclib in a lead-in phase and after palbociclib dose on cycle 1 day 21 for multiple dose pharmacokinetic evaluation. Predose blood samples for pharmacokinetic evaluation of palbociclib and letrozole were collected on days 19–21 of cycle 1 and cycle 2 day 1 (letrozole only). Disease assessments were done every 12 weeks from cycle 1 day 1. Safety was assessed per Common Terminology Criteria for Adverse Events, version 4.0. This study is registered with ClinicalTrials, number NCT02499146, and is ongoing but not recruiting. Findings As of March 16, 2016, the cutoff date, the study completed enrolment with 26 patients. All patients completed single dose pharmacokinetic evaluation and 13 completed multiple dose pharmacokinetic evaluation. After multiple doses, the steady-state palbociclib geometric mean area under the concentration–time curve from 0 to 24 h was 2005 ng × h/mL and maximum observed concentration was 112·3 ng/mL, similar to those obtained in Caucasian patients following the same dosing regimen. Comparisons of single dose and multiple dose pharmacokinetic data indicated linear pharmacokinetics of palbociclib. The geometric mean accumulation ratio of palbociclib exposure after multiple dose compared with single dose was 2·1, consistent with a terminal half-life of 23·4–27·5 h. Trough concentrations of letrozole were similar to concentrations obtained in Caucasian patients. No deaths or permanent discontinuations due to adverse events were reported. One serious adverse event occurred but was not considered to be treatment-related. The most common clustered adverse events were neutropaenia (n=20, 77%), leukopaenia (n=19, 73%), and anemia (n=11, 42%), with neutropaenia (n=15, 58%) and leukopaenia (n=8, 31%) the most common grade 3–4 adverse events. Interpretation No dose adjustment for palbociclib is needed based on the Chinese population. The toxicity of palbociclib in combination with letrozole treatment was tolerable and manageable. Funding Pfizer Inc.

[A multicenter, randomized, controlled, phase III clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer].

OBJECTIVE To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application. METHODS According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle. RESULTS The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581). CONCLUSIONS In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.