Background: Neutropenia is a common complication from chemotherapy. Mecapegfilgramtim (code name HHPG-19K), a long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF), has been developed. This study was to evaluate the efficacy and safety of mecapegfilgrastim for reducing neutropenia compared with filgrastim.Methods: This was a randomized, controlled non-inferiority study. A total of 339 breast cancer patients who were eligible for (neo) adjuvant chemotherapy were randomized assigned into three groups to receive mecapegfilgrastim 100 µg/kg, mecapegfilgrastim fixed dose of 6 mg or filgrastim 5 µg/kg/day in the first cycle of chemotherapy. The primary endpoint was the duration of grade ≥3 neutropenia in cycle 1. The secondary endpoints included the duration of grade ≥3 neutropenia in cycles 2-4, incidence of grade ≥3 neutropenia, and febrile neutropenia (FN). The safety profile was also evaluated. Results: The mean duration of grade ≥3 neutropenia was 1.06 [95% confidence interval (CI): 0.65, 1.26] days in mecapegfilgrastim 100 µg/kg group, 1.23 (95% CI: 0.84, 1.88) days in mecapegfilgrastim 6 mg group, and 2.06 (95% CI: 1.66, 2.46) days in the filgrastim group. The mean difference between mecapegfilgrastim 100 µg/kg and filgrastim was -1.00 (95% CI: -1.52, -0.48), the mean difference between mecapegfilgrastim 6 mg and filgrastim was -0.83 (95% CI: -1.36, -0.30). The upper bounds of 95% CI for the difference between mecapegfilgrastim and filgrastim were all <1 day (the predefined non-inferiority margin). For the incidence of grade ≥3 and grade 4 neutropenia, the mean duration of grade 4 neutropenia, mecapegfilgrastim showed better performance compared with filgrastim. For the incidence of FN, there was no difference between patients treated with mecapegfilgrastim and filgrastim. For safety profile, mecapegfilgrastim of two doses groups were all well-tolerated. Fixed 6 mg dose of mecapegfilgrastim exhibited comparable efficacy and safety in comparison with 100 µg/kg during 4 cycles.Conclusions: Long-acting mecapegfilgrastim (100 µg/kg and fixed 6 mg) is very effective and well tolerated when administered in the primary prophylaxis of chemotherapy induced neutropenia and in Xu et al. Mecapegfilgrastim for neutropenia in breast cancer

can be considered during the neoadjuvant treatment in all patients who qualify for single-targeted therapy. 2 The KRISTINE study (1) confirmed the effectiveness and safety of TCbHP regimen in neoadjuvant treatment, Therefore, TCbHP is the preferred regimen in preoperative treatment. 3 The NeoSphere study (2) confirmed that adding pertuzumab to TH could further increase the pCR rate in HER-2-positive patients. However, in the above study, surgery was performed after 4 cycles of neoadjuvant treatment with THP, and the dualtargeted therapy was suspended after surgery and then continued after 3 cycles of FEC therapy. The clinical feasibility of this protocol was quite questionable. 4 The TCbH regimen has been demonstrated to be effective and safe in preoperative neoadjuvant therapy and postoperative adjuvant therapy and thus can be recommended for neoadjuvant therapy (3). 5 Based on the findings of research on AC→TH regimen in the single-targeted era, some experts agree that AC→THP can be used as an optional regimen for neoadjuvant therapy, which, however, has not been validated in well-designed clinical studies. 6 According to the GBG69 study (4), albumin paclitaxel has a higher pCR rate than solvent-based paclitaxel in neoadjuvant therapy and it can also improve patients' disease-free survival (DFS). Thus, albumin paclitaxel can also be an optional drug in neoadjuvant therapy. Adjuvant treatment for HER-2-positive patients after neoadjuvant therapy 1As more HER-2-positive breast cancer patients receive neoadjuvant treatment, the strategies of postoperative adjuvant treatment have also changed. Accordingly, the 2020 version of these Guidelines recommends the following adjuvant treatments for HER-2-positive patients who have received neoadjuvant treatment:

PURPOSE To examine the impact of a clinical decision support system (CDSS) on breast cancer treatment decisions and adherence to National Comprehensive Cancer Center (NCCN) guidelines. PATIENTS AND METHODS A cross-sectional observational study was conducted involving 1,977 patients at high risk for recurrent or metastatic breast cancer from the Chinese Society of Clinical Oncology. Ten oncologists provided blinded treatment recommendations for an average of 198 patients before and after viewing therapeutic options offered by the CDSS. Univariable and bivariable analyses of treatment changes were performed, and multivariable logistic regressions were estimated to examine the effects of physician experience (years), patient age, and receptor subtype/TNM stage. RESULTS Treatment decisions changed in 105 (5%) of 1,977 patients and were concentrated in those with hormone receptor (HR)–positive disease or stage IV disease in the first-line therapy setting (73% and 58%, respectively). Logistic regressions showed that decision changes were more likely in those with HR-positive cancer (odds ratio [OR], 1.58; P < .05) and less likely in those with stage IIA (OR, 0.29; P < .05) or IIIA cancer (OR, 0.08; P < .01). Reasons cited for changes included consideration of the CDSS therapeutic options (63% of patients), patient factors highlighted by the tool (23%), and the decision logic of the tool (13%). Patient age and oncologist experience were not associated with decision changes. Adherence to NCCN treatment guidelines increased slightly after using the CDSS (0.5%; P = .003). CONCLUSION Use of an artificial intelligence–based CDSS had a significant impact on treatment decisions and NCCN guideline adherence in HR-positive breast cancers. Although cases of stage IV disease in the first-line therapy setting were also more likely to be changed, the effect was not statistically significant ( P = .22). Additional research on decision impact, patient-physician communication, learning, and clinical outcomes is needed to establish the overall value of the technology.

Background: To compare the efficacy and safety of pyrotinib and trastuzumab emtansine (T-DM1) in patients who experienced disease progression on trastuzumab and lapatinib treatment. Methods: This was a real-world study that included cases of metastatic breast cancer (MBC) with trastuzumab and lapatinib failure. One group of patients received pyrotinib monotherapy or combination therapy, whereas the other group received T-DM1 monotherapy. The primary study endpoint was progression-free survival (PFS); secondary endpoints were the objective response rate (ORR), clinical benefit rate (CBR) and safety. Results: Between January 2013 and November 2019, 105 patients were enrolled in the pyrotinib group (n=55) or T-DM1 group (n=50). The median PFS was 6.0 months (95% CI, 4.7 to 7.3 months) with pyrotinib and 4.2 months (95% CI, 3.6 to 4.8 months) with T-DM1 (P=0.044). ORR values were 16.3% and 20.0% in the pyrotinib and T-DM1 groups, respectively (P=0.629); CBR values were 45.5% and 40.0%in the pyrotinib and T-DM1 groups, respectively (P=0.573). Subgroup analysis of those benefitting from lapatinib revealed a median PFS of 8.1 months (95% CI, 4.8 to 11.4 months) in the pyrotinib group, whereas that of the T-DM1 group was 4.4 months (95% CI, 3.8 to 5.0 months, P=0.013). Moreover, the median PFS of patients without liver metastases was 6.9 months (95% CI, 3.7 to 10.1 months) in the pyrotinib group and 4.1 months (95% CI, 3.1 to 5.1 months) in the T-DM1 group (P=0.010). The main common adverse events (AEs) were diarrhea (98.2%) and nausea (49.1%) in the pyrotinib group and thrombocytopenia (42.0%) and nausea (40.0%) in the T-DM1 group. The percentages of grade 3 to 4 AEs in the pyrotinib and T-DM1 groups were 34.5% and 40.0%, respectively. Conclusions:The results of this study suggest that patients with HER2-positive MBC with trastuzumab and lapatinib failure can benefit from subsequent pyrotinib treatment and tolerate this treatment well, especially those who have benefited from previous lapatinib treatment or those who have no liver metastasis.

Background: Somatic mutations in ERBB2 are a new class of oncogenic drivers in HER2–non amplified MBC. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor that inhibits the growth of ERBB2-mutant breast tumors in preclinical models and has encouraging single-agent clinical activity in patients (pts) with ERBB2-mutant, HER2–non amplified MBC. Bi-directional signaling between HER2 and ER may limit the effectiveness of endocrine and HER2 directed therapy, if each is given alone, in ER+ MBC with ERBB2 amplifications/mutations. Preclinical data suggest that dual blockade of ER and HER2 signaling results in enhanced anti-tumor activity in ER+ HER2+ MBC. SUMMIT, a multicenter multi-histology phase II 'basket' trial, is investigating the efficacy of neratinib monotherapy (in ER+ and ER– pts) and neratinib + fulvestrant (ER+ pts only) in ERBB2-mutant MBC. Methods: MBC pts with ERBB2 mutations documented by local testing were eligible and received oral neratinib 240 mg qd. Pts with ER+ MBC received fulvestrant 500 mg, a selective ER degrader, in addition to neratinib on d1 & 15 of month 1 then on d1 q4w. Patients received high dose loperamide prophylaxis during cycle 1. Primary endpoint is objective response rate (ORR) at 8w, defined using RECIST 1.1 and/or modified PERCIST assessments. Secondary endpoints include ORR, clinical benefit rate (CBR), progression free survival (PFS), and safety. Mutation profiling and central confirmation of ERBB2 mutation(s) from available fresh or archival tumor tissues and plasma DNA were performed retrospectively by next-generation sequencing (MSK-IMPACT). Clinicaltrials.gov: NCT01953926. Results: As of 23 Sep 2016, 35 efficacy-evaluable ERBB2-mutant MBC pts received neratinib, either as monotherapy (n=24) or in combination with fulvestrant (n=11). Efficacy findings are shown in the table. The overall safety profile of neratinib + fulvestrant was similar to that previously reported with neratinib monotherapy. Grade 3 diarrhea rate was 24% with neratinib monotherapy and 18% with neratinib + fulvestrant. Neratinib monotherapyNeratinib + fulvestrant(n=24)(n=11)Best Overall Response (confirmed and unconfirmed), n (%)8 (33.3)6 (54.5)[95% CI][15.6–55.3][23.4–83.3]CR3 (12.5)2 (18.2)PR5 (20.8)4 (36.4)aORR at 8 weeks, n (%)8 (33.3)5 (45.5)[95% CI][15.6–55.3][16.7–76.6]CR2 (8.3)2 (18.2)PR6 (25.0)3 (27.3)ORR confirmed, n (%)5 (20.8)2 (18.2)b[95% CI][7.1–42.2][2.3–51.8]CR3 (12.5)1 (9.1)PR2 (8.3)1 (9.1)CBR, n (%)10 (41.7)6 (54.5)[95% CI][22.1–63.4][23.4–83.3]CR, complete response; PR, partial response.aThere was 1 pt with PR at week 16; bAt time of data cut-off 4 pts are still on treatment. Conclusions: Encouraging clinical activity has been observed with neratinib + fulvestrant in heavily pretreated pts with ERBB2-mutant, ER+ MBC. Clinical efficacy in the ER+ MBC cohort met pre-specified efficacy requirements; a confirmatory trial of neratinib + fulvestrant for targeting ERBB2 mutations in ER+ MBC is warranted. The safety profile of neratinib was acceptable and diarrhea was manageable with loperamide prophylaxis. Citation Format: Hyman D, Piha-Paul S, Saura C, Arteaga C, Mayer I, Shapiro G, Loi S, Lalani A, Xu F, Cutler R, Butturini A, Bryce R, Meric-Bernstam F, Baselga J, Solit D. Neratinib + fulvestrant in ERBB2-mutant, HER2–non-amplified, estrogen receptor (ER)-positive, metastatic breast cancer (MBC): Preliminary analysis from the phase II SUMMIT trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD2-08.