Search

PURPOSE Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study. PATIENTS AND METHODS Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m2 orally twice per day on days 1 to 14). The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS Between May 29, 2015, and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n = 65) or lapatinib (n = 63) treatment groups. The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01). The median progression-free survival was 18.1 months (95% CI, 13.9 months to not reached) with pyrotinib and 7.0 months (95% CI, 5.6 to 9.8 months) with lapatinib (adjusted hazard ratio, 0.36; 95% CI, 0.23 to 0.58; P < .001). The most frequent grade 3 to 4 adverse events were hand-foot syndrome in 16 of 65 patients (24.6%) in the pyrotinib group versus 13 of 63 (20.6%) in the lapatinib group; diarrhea in 10 patients (15.4%) versus three patients (4.8%), respectively; and decreased neutrophil count in six patients (9.2%) versus two patients (3.2%), respectively. CONCLUSION In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.

1031 Background: HER2-targeted agents have improved outcomes in HER2-positive breast cancer, but some pts develop resistance, relapse, or do not respond to current 1L therapies. Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2. In a Phase 1 trial (NCT02892123) zani was well tolerated and demonstrated preliminary antitumor activity as monotherapy/with chemotherapy in pts with pre-treated advanced HER2+ breast cancer. Methods: Cohort 1 of this ongoing open-label, Phase 1b/2 study (NCT04276493) is evaluating zani in combination with docetaxel as a 1L therapy in adult females with advanced HER2+ breast cancer who may have received prior neoadjuvant/adjuvant treatment. Cohort A pts received zani 30 mg/kg IV, Cohort B pts received zani 1800 mg IV, both with docetaxel 75 mg/m2 IV Q3W. Primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS). Results: As of Nov 26, 2021, 25 pts with a median age of 57.0 years (range: 33.0–80.0) were assigned to Cohort A (n=11) or B (n=14). Median study follow-up was 7.0 months (range: 1.1–17.4) and the median number of treatment cycles was 10 (range: 2–20), 16 (64.0%) pts remained on treatment. Of the 22-efficacy evaluable (EE) pts, confirmed ORR was 86.4% (95% CI: 65.1, 97.1). The 6 months PFS rate was 90.9% (95% CI: 68.3, 97.7). Efficacy data are summarized in Table 1. All pts experienced ≥ 1 treatment emergent adverse event (TEAE) and 17 (68.0%) pts experienced ≥ Grade 3 TEAEs. In total, 23 (92.0%) pts experienced treatment related TEAEs (trTEAEs), and 17 (68.0%) pts experienced ≥ Grade 3 trTEAEs. The most common trTEAEs were diarrhea (56.0%) and decreased neutrophil count (52.0%). Serious trTEAEs occurred in two (8.0%) pts, trTEAEs leading to treatment discontinuation occurred in one (4.0%) pt and no trTEAEs led to death. Conclusions: Zani and docetaxel combination demonstrated antitumor activity in 1L therapy for advanced HER2+ breast cancer, with a manageable safety profile. Clinical trial information: NCT04276493. [Table: see text]

2526 Background: This phase III study compared clinical efficacy, safety of the first biosimilar QL1206 with denosumab in solid tumor patients with bone metastases. Methods: Patients aged 18-80 years, with bone metastatic solid tumors and ECOG performance status of 0-2 were randomly assigned 1:1 to receive subcutaneous QL1206 or denosumab (120 mg Q4W, both) based on stratification factors (tumor types, previous skeletal-related event [SRE], and current systemic anti-tumor therapy). The primary efficacy endpoint was the percentage changes from baseline to week 13 in urinary N-telopeptide/creatinine ratio (uNTX/uCr); Clinical equivalence would be confirmed if the two-sided 90% confidence intervals (CI) of the least-squares mean (LSM) difference of natural log-transformed ratio of week 13 uNTX/uCr to baseline calculated by analysis of covariance were within the margins of ±0.135. The secondary endpoints included the percentage changes from baseline to week 25 and 53 in uNTX/uCr, the percentage changes from baseline to week 13, 25 and 53 in serum bone-specific alkaline phosphatase (s-BALP) and the time to on-study SRE. Adverse events (AE), immunogenicity (IG) and pharmacokinetics (PK) were also assessed. Population PK was analyzed using nonlinear mixed effects model. Results: 717 patients were randomized to the QL1206 (n = 357) and denosumab (n = 360) groups, respectively. The median percentage changes at week 13 in uNTX/uCr were -75.2% for QL1206 and -75.8% for denosumab. LSM of natural log-transformed ratio of week 13 uNTX/uCr to baseline were -1.429 (standard error 0.130) and -1.441 (0.130) in the two groups. The LSM difference between the two groups was 0.012 (90% CI -0.078 to 0.103; P = 0.8208), within the equivalence margins. Analyses for subgroups of sex, age, and randomization strata showed almost no significant differences. The secondary endpoints were also similar between the two groups (median percentage changes in s-BALP from baseline to week 13: -38.0% vs -37.1%; hazard ratio of time to SRE: 1.264 [95% CI 0.670 to 2.383]; both P > 0.05). In the safety set, treatment-emergent AE occurred in 332 of 356 patients (93.3%) in the QL1206 group and 348 of 361 (96.4%) in the denosumab group. The proportions of positive anti-drug antibody (14/345 [4.1%] vs 16/352 [4.5%]), neutralizing antibody (three [0.9%], each), and PK characteristics were similar between the two groups. Conclusions: The results suggest that QL1206, the first biosimilar denosumab, is similar to denosumab with respect to clinical efficacy, acceptable safety, IG, and PK characteristics. The totality of evidence supports clinical equivalence of QL1206 and denosumab. Clinical trial information: NCT04550949.

e13050 Background: This study was to compare the efficacy and safety of different nab-paclitaxel dose schedule in patients with HER-2 negative recurrent/metastatic breast cancer in order to find a more suitable treatment option for Chinese patients. Methods: This is a single-center, open-label, randomized, phase II trial. Eligible female patients with HER-2 negative recurrent/metastatic breast cancer and up to 2 lines of prior chemotherapy regardless of any endocrine therapy were randomly assigned (1:1) to either nab-paclitaxel (125mg/m2 IV days 1, 8, every 21 days, 3-week group) or nab-paclitaxel (125mg/m2 IV days 1, 8, 15, every 28 days, 4-week group) until progressive disease or completion of 6-8 cycles of treatment. After completing 6-8 cycles, if the efficacy evaluation is CR, PR or SD, the investigator can decide whether to carry out maintenance therapy. The primary endpoint is PFS. Secondary endpoints are ORR, OS and safety. Results: Between March 2019 and July 2021, 104 patients with HER-2 negative breast cancer were randomly assigned to treatment (3-week group, n = 51; 4-week group, n = 53). Median follow-up was 16.4 and 15.8 months. In the 3-week and 4-week groups, respectively, 39 (76.5%) and 42 (79.2%) patients had HR positive disease and 37 (72.5%) and 43 (81.1%) patients had visceral metastasis. In two groups, respectively, 30 (58.8%) and 20 (37.7%) patients didn’t receive prior endocrine therapy. 20 (39.2%) and 32 (60.4%) patients had received 1 to 3 lines of prior endocrine therapy. 30 (58.8%) patients of 3-week group and 30 (56.6%) patients of 4-week group were enrolled at first-line chemotherapy, and 13 (25.5%) of 3-week group patients and 16 (30.2%) patients of 4-week group were enrolled at second-line chemotherapy, as third-line chemotherapy there were only 8 (15.7%) in 3-week group and 7 (13.2%) in 4-week group. Among all patients, 33 (64.7%) in the 3-week group and 16 (30.2%) in the 4-week group had received 6-8 cycles according to the regimen of study, and 32 (97.0%) of 3-week group and 15 (93.8%) of 4-week group patients who finished the regimen choose to receive maintenance treatment (endocrine or chemotherapy).In two groups, respectively, median PFS was 9.6 months and 7.5 months (HR 0.905; 95%CI 0.569-1.440) and ORR were 50.0% (23/46) and 46.9% (23/49) in the evaluable population. Median OS was 22.5 months in the 3-week group and has not yet been reached for the 4-week group. According to NCI-CTCAE V5.0, 3-week group vs 4-week group respectively, the grade 3-4 adverse events (≥2 patients) were neutropenia (13.7% vs 34.0%), leukopenia (7.8% vs 17.0%) and peripheral neurotoxicity (0 vs 3.8%). Conclusions: Preliminary results suggest that compared with the 4-week regimen, the 3-week regimen of nab-paclitaxel seems to be more suitable and adaptable for Chinese patients with advanced breast cancer. This study is still in follow-up and updated data will be presented. Clinical trial information: NCT04192331.

5539 Background: The combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor has demonstrated improved clinical outcomes as treatment/maintenance treatment in gynecological cancers. Here we aimed to characterize the safety profile and recommended phase 2 dose (RP2D) of the combination of fuzuloparib (formerly fluzoparib), a PARP inhibitor, and apatinib, a VEGFR inhibitor in recurrent ovarian cancer (OC) or triple-negative breast cancer (TNBC). Methods: This was a dose-escalation and PK-expansion phase 1 trial conducted in China. Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer or metastatic TNBC were eligible. No prior PARP/VEGFR inhibitors were allowed. The study used a standard 3+3 dose-escalation design, with additional patients (a total of 8-12 patients per dose level) enrolled for PK assessment. Patients received orally a single dose of fluzoparib on D1 and apatinib on D4, followed by continuous dosing of fluzoparib (bid) plus apatinib (qd) starting on D8. Endpoints were RP2D, safety, PK, and anti-tumor activity. Results: Between 03/17/2017 and 03/02/2021, 52 patients (30 OC, 22 TNBC) were enrolled to 7 dose levels (up to fuzuloparib 100 mg plus apatinib 500 mg). A total of 2 DLTs occurred: grade 4 decreased white blood cell count (WBC)/febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and grade 4 thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). No maximum tolerated dose was reached. The most common treatment-related grade ≥3 toxicities included hypertension, anemia/decreased hemoglobin, thrombocytopenia, and decreased WBC. In PK analysis, steady-state plasma concentrations of apatinib was decreased when combined with fuzuloparib, as compared with apatinib alone. Higher dose of apatinib in combination with fuzuloparib 100 mg was associated with higher exposure and improved clinical activity. The ORR was 44% (95% CI, 32-58; OC, 60% [95% CI, 42-75]; TNBC, 23% [95% CI, 10-43]) across all dose levels and 62.5% (95% CI, 31-86) at fuzuloparib 100 mg plus apatinib 500 mg (all OC), which was determined to be the RP2D. Conclusions: Fuzuloparib plus apatinib has acceptable safety in patients with recurrent ovarian cancer and triple-negative breast cancer. With the promising clinical activity observed in ovarian cancer, this combination is warranted to be further explored as a potential alternative to chemotherapy. Clinical trial information: NCT03075462.

1019 Background: Androgen receptor (AR) is an emerging prognostic marker and therapeutic target in breast cancer. AR is expressed in 60% to 80% of breast cancers. Recent studies have shown the association between AR signaling and tumor carcinogenesis in breast cancer, suggesting AR pathway as a potential target for breast cancer treatment. However, no AR targeting therapies have been approved for treating breast cancer. GT0918 is a new chemical entity of AR antagonist with possible AR down-regulation. We had finished the phase I study and submitted the paper. Here we present a multicenter, open-label phase Ib trial assessing the safety and efficacy of GT0918 in women with AR positive metastatic breast cancer. The primary objective is to evaluate the efficacy of GT0918. The secondary objectives are to assess its safety and to explore the relevant biomarkers. Methods: This is an expansion study of a phase I dose-escalation trial. In this phase Ib study, only patients with AR positive metastatic breast cancer were enrolled. All eligibled patients would take GT0918 orally once a day, of a 28 -day cycle. After 2 cycles’ safety and tolerability assessment, patients could choose to continue their treatment until they experience disease progression, intolerable toxicities, death, or withdrew consent. The primary efficacy endpoints were 8-week disease control rate (DCR) and 16-week DCR. The secondary efficacy endpoint was progression free survival (PFS). Results: In total, 45 patients were enrolled in the study at 200mg (n = 30) and 300mg (n = 15) doses. The most common (≥10%) treatment-related adverse events (AEs) were asthenia (42.2%), aspartate aminotransferase increased (26.7%), blood cholesterol increased(17.8%), alanine aminotransferase increased (17.8%), decreased appetite (17.8%), blood triglycerides increased (13.3%), blood lactate dehydrogenase increased (13.3%), anaemia (13.3%), blood alkaline phosphatase increased (11.1%), gamma-glutamyltransferase increased (11.1%), urinary tract infection (11.1%). Grade 3/4 AEs were reported in 9 patients (20%). No treatment-related deaths occurred. The 8-week and 16-week DCR were both 22.2% (n = 10) (95% CI 10.08%, 34.37%). The median PFS was 1.8 months (95% CI 1.8, 1.9) in all patients. 12 out of 45 (26.7%) were triple negative breast cancer cases. The median PFS was 1.9 months (95% CI 1.7, 9.1), 4 out of 12 patients (33.3%) > 6 months, 2 out of 12 patients (16.7%) > 9 months. Conclusions: GT0918 has been shown to be well tolerated and may provide potential clinical benefits to AR positive metastatic breast cancer patients. This study demonstrated triple negative in AR positive patients had more benefit. Clinical trial information: NCT04103853 .

e24070 Background: Neutropenia is the frequently observed adverse events for breast cancer patients under chemotherapy. Prophylactic administration of mecapegfilgrastim could reduce the incidence of grade 3/4 neutropenia/febril neutropenia(FN). The effectiveness of mecapegfilgrastim in breast cancer patients and different subgroups were explored. Methods: Patients with breast cancer and tolerable of mecapegfilgrastim were prospectively enrolled in a real-world study. All the patients received mecapegfilgrastim prophylacticly at least in chemotherapy cycle one. The incidence of grade 3/4 neutropenia/febril neutropenia in all patients and subgroups were presented. Results: 322 eligible patients were enrolled. The median age was fifty one years. The ECOG performace score was 0 – 1. In total, 752 chemothrapy cycles were conducted. Grade 3/4 neutropenia occurred in 44 (5.9 %) cycles, grade 4 neutropenia occurred in 16 (2.1 %) cycles. FN were reported in 4 (1.2 %) patients. The incidence of grade 3/4 neutropenia were stratificated by age group (≥65, ＜65), chemotherapy history, radiotherapy history, baseline absolute white blood cell count (≥4.0 ×109/L, ＜4.0 ×109/L), baseline absolute neutrophil count (≥2.0 ×109/L, ＜2.0 ×109/L), baseline hemoglobin level (≥110 g/L, ＜110 g/L) and chemotherapy regimens (High risk of FN, intermediate risk of FN). The results showed that patients with baseline hemoglobin of ≥110 g/L and ＜110 g/L had grade 3/4 neutropenia of 5% and 14.8 % respectively (P = 0.017). Patients treated with high FN risk chemotherapy and intermediate FN risk chemotherapy had grade 3/4 neutropenia of 0.9 % and 8.9 % respectively (P = 0.003). No significant difference of incidence of grade 3/4 neutropenia between other subgroups were found. Patients treated with cyclophosphamide and epirubicin (AC, classified as intermediate risk of FN by investigator) had grade 3/4 neutropenia of 15.4 %; Patients treated with cyclophosphamide, docetaxel and epirubicin (TAC, classified as high risk of FN by investigator) had grade 3/4 neutropenia of 14.3 %; Patients treated with docetaxel monotherapy (classified as intermediate risk of FN by investigator) had grade 3/4 neutropenia of 4.9 %. Conclusions: Prophylactic administration of mecapegfilgratim reduced the incidence of grade 3/4 neutropenia/febril neutropenia. Baseline hemoglobin level and specific chemotherapy regimen could be a useful prognostic facots for neutropenic events after administered mecapegfilgrastim.

1039 Background: KAMILLA is an open-label, single-arm, phase 3b safety study of T-DM1 in pts with HER2-positive advanced BC (NCT01702571). The treated (safety) population of KAMILLA comprises 2 cohorts: a larger global Cohort 1 (n=2002) and a smaller Asia Cohort 2 (n=181 [China, n=154; Thailand, n=15; Indonesia, n=12]). Here we report results from Cohort 2 in the context of those previously reported for Cohort 1. Methods: Pts had HER2-positive, locally advanced or mBC with progression after chemotherapy and anti-HER2 therapy or ≤6 months (mo) of completing adjuvant therapy. T-DM1 3.6 mg/kg was given intravenously every 3 weeks until disease progression, consent withdrawal, or unacceptable toxicity. Primary endpoints were grade ≥3 (G≥3) adverse events of primary interest (AEPIs), specifically hepatic events, allergic reactions, thrombocytopenia (TCP), and hemorrhage events; all other G≥3 treatment-related AEs (TRAEs); and all-grade pneumonitis. Results: As of 31 July 2019,KAMILLA enrolled 2185 pts (Cohort 1, n=2003; Cohort 2, n=182), of which 2002 and 181 in each cohort, respectively, received ≥1 study dose and were included in the safety population. Baseline characteristics were generally similar between cohorts. Median (range) T-DM1 exposure was 5.6 mo (0–46) for Cohort 1 and 5.0 mo (0–31) for Cohort 2. The overall G≥3 AEPI rate was higher in Cohort 2 vs Cohort 1 (Table), mostly driven by a higher G≥3 TCP rate in Cohort 2. In Cohort 2, G≥3 TCP (the most frequently reported G≥3 AEPI) did not appear to be associated with G≥3 hemorrhagic events — the majority of G≥3 TCP events (128/138) fully resolved, with a duration of ≤15 days for 98/138 of these events. G≥3 TRAE rates were 18.4% in Cohort 1 and 48.6% in Cohort 2, the latter mainly due to TCP and platelet count decreased; any-grade pneumonitis rates were 1.0% and 2.2%, respectively. No other safety signals were identified. Median progression-free survival and overall survival were similar for both cohorts (Table). Conclusions: These data confirm prior observations in an Asian subgroup of the phase 3 EMILIA trial of T-DM1 in pts with previously treated mBC. Although the G≥3 TCP rate was higher in the Asia cohort, the majority of these events resolved fully. OS and PFS were similar in both cohorts. These data reinforce the favorable T-DM1 benefit-risk profile in mBC. Clinical trial information: NCT01702571 .[Table: see text]

1003 Background: Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine showed clinically meaningful benefits and acceptable tolerability in patients (pts) with HER2+ metastatic breast cancer (MBC) in phase 1 and 2 studies. Methods: This open-label, multicenter, randomized phase 3 study enrolled HER2+ MBC pts after trastuzumab and taxanes, and/or anthracyclines. Up to two prior lines of chemotherapy (chemo) for metastatic disease were allowed. Pts were randomly assigned (1:1) to receive pyrotinib 400 mg or lapatinib 1250 mg qd continuously plus capecitabine 1000 mg/m2 bid on days 1–14 of 21-day cycles. The primary endpoint was progression-free survival (PFS) per blinded independent central review. Results: From Jul 2017 to Oct 2018, 267 pts were randomized to the pyrotinib (n=134) or lapatinib (n=133) arm. One pt in the lapatinib arm did not receive study treatment and was excluded from analyses. 42.5% and 34.8% of pts in the pyrotinib and lapatinib arm had no prior chemo for metastatic disease, 41.8% and 49.2% had one prior line, and 15.7% and 15.9% had two lines. At the planned interim analysis, the median PFS was 12.5 months (95% CI 9.7–not reached) with pyrotinib plus capecitabine vs 6.8 months (95% CI 5.4–8.1) with lapatinib plus capecitabine (HR 0.39 [95% CI 0.27–0.56]; P

3638 Background: Bone is one of the most common metastatic sites of malignancies. The metastatic tumor cells activate osteoclast activity and promote bone resorption via RANKL/RANK signaling pathway, and lead to osteolytic destruction. JMT103 is an innovative fully human IgG4 monoclonal antibody targeting RANKL. It can block RANKL/RANK signaling pathway, inhibit bone resorption, and protect bones from tumor metastasis. This study aimed to evaluate the safety and tolerability of JMT103 in patients with bone metastasis. Methods: This is a multi-center, open label, dose escalation, phase I clinical trial. The patients (ECOG score: 0-1) with bone metastasis from solid tumor who had not received bisphosphonates within 6 weeks before enrollment and were naïve to denosumab were enrolled. The initial dose was 0.5 mg/kg, sequentially escalated to 1.0, 2.0, and 3.0 mg/kg. JMT103 was injected subcutaneously by accelerated titration in 0.5 and 1.0 mg/kg dose groups, but via traditional "3+3" dose-escalation design in 2.0 and 3.0 mg/kg dose groups. Expansion study was conducted for subjects in 1.0, 2.0, and 3.0 mg/kg dose groups. Specifically, 3 additional doses (q4w) were injected after the end of 12-week single-dose study. The primary endpoints were maximum tolerated dose and safety. The secondary outcome measures included PK profile, preliminary efficacy biomarkers, immunogenicity, and bone mineral density (BMD). Results: From May 2018 to January 2020, 56 patients (13 males, 43 females, mean (SD) age: 55.57 (11.42) years) were enrolled, including bone metastasis from breast cancer (n = 36), gastric cancer (n = 5), lung cancer (n = 4), rectal cancer (n = 3), colorectal cancer (n = 2), or other solid tumors (n = 6). Nineteen patients participated in the dose-escalating study and 37 patients participated in the expansion study. JMT103 showed overall good safety. There were 74 drug-related AEs in all, including grade 3 (DLT hypocalcemia, n = 1; hypophosphatemia, n = 3), grade 2 (n = 15), and grade 1 (n = 55) AEs. The most common drug-related AEs were hypophosphatemia (n = 15), hypocalcemia (n = 12), and hypermagnesemia (n = 6). Median uNTx/Cr decrease from baseline was 76.6% (n = 20). Conclusions: JMT103 shows good safety and tolerability in patients with bone metastasis. Clinical trial information: NCT03550508 .

1059 Background: Metastatic breast cancer (MBC) is a heterogeneous disease associated with known somatic mutations of variable biological value in different subtypes. Furthermore, the clinical evolution of the disease demonstrates clonal evolution resulting in disease resistance more accurately detected using blood-based sequencing. Few studies have explored differences in genomic features of tumors across populations. Here, we performed circulating tumor DNA (ctDNA) sequencing to compare the genomic landscape of patients with hormone-receptor positive MBC at time of first recurrence or de-novo metastatic diagnosis in the United States (US) and China. Methods: Twenty-three US patients from Northwestern University and 65 Chinese patients from Peking University had ctDNA sequencing from plasma performed using the harmonized CLIA-certified, 152-gene PredicineCARE assay in laboratories in the US and China, respectively. The data analysis was conducted in China. Institutional Review Boards at each site approved the study. Fisher’s exact test was performed to compare mutational frequencies across populations. Results: Median age of patients at MBC diagnosis was 51 in the US cohort and 55 in the Chinese cohort. 87% of US patients and 82% of Chinese patients had received prior therapy for primary breast cancer, including endocrine therapy. Mutations were detected in 17 of 23 (74%) US patients and 59 of 65 (91%) Chinese patients. CNAs were observed in 57% of US patients and 58% of Chinese patients. The most common mutations detected in US patients were TP53 (26%), PIK3CA (22%), AKT1 (22%), CDH1 (17%), PTEN (13%), and ESR1 (9%) vs. PIK3CA (46%), TP53 (35%), ESR1 (12%), and BRCA2 (11%) in Chinese patients. Frequency of AKT1 and CDH1 mutations were significantly higher in the US population (P < 0.05), while PIK3CA mutations were higher in the Chinese population (P < 0.05). CNA gains in CCND3 and CDK4 were significantly higher in the US cohort, and FGFR1 was significantly more common in the Chinese cohort (all P < 0.05). Conclusions: To our knowledge, this is a first cross-regional comparison study in HR+ MBC patients in the US and China using a harmonized cfDNA NGS platform. At a population level, there were notable differences observed in somatic variants in two cohorts. Future sequencing efforts and clinical trials should include patients of diverse ethnic backgrounds to explore the impact of differences in genomic landscape on probability of benefit from treatments. A larger validation cohort is required to confirm these findings.

e19051 Background: This study was to evaluate the efficacy and safety of PEG-rhG-CSF (brand name:jinyouli) in primary and secondary prevention of CIN(chemotherapy-induced neutropenia). Methods: This is a single-center,one-arm clinical study.Patients with non-myeloid malignant tumors were enrolled. PEG-rhG-CSF was given subcutaneously at 24-48h after chemotherapy. The indicator was febrile neutropenia(FN) and IV grade absolute neutrophil count. Results: From January 2016 until June 2018,217 patients were enrolled including 119 lymphoma patients, 50 breast cancer patients, 30 bone tumor patients,18 gynecologic oncology patients, and While146 with primary prevention and 71 with secondary prevention. The incidence of FN was 5.0% (35/692), which was 4.3% (21/478) in the primary prevention patients and 6.5% (14/214) in the secondary prevention patients ( p= 0.233).Logistic regression analysis showed that the longer the treatment cycle, the lower the incidence of FN. Comparison of the indicators of different chemotherapy cycles showed that the IV grade absolute neutrophil count (ANC) reduction was significantly lower in the primary prevention patients than in the secondary prevention patients in the first cycle of chemotherapy[17.1%(25/146) vs.46.5%(33/70),p = 0.000],the incidence of FN and IV grade ANC reduction were significantly lower in the second cycle of treatment than in the first cycle(p < 0.05).The adverse event were mainly bone pain, the incidence of 1/2 grade bone pain was 3.7% (8/217) and the incidence of grade 3/4 bone pain was 1.8% (4/217). Conclusions: The prevention of CIN with PEG-rhG-CSF after chemotherapy can effectively reduce the incidence of FN.For the first chemotherapy cycle, primary prevention is more effective than secondary prevention in preventing the incidence of IV grade ANC reduction. Clinical trial information: NCT02905916.

1026 Background: In CLEOPATRA (NCT00567190), adding P to H + D significantly improved progression-free and overall survival (PFS/OS) v Pla + H + D in patients (pts) with previously untreated HER2-positive LR/MBC. PUFFIN (NCT02896855) is a China bridging study; the objective being to assess consistency of efficacy with CLEOPATRA. Methods: Pts with previously untreated HER2-positive LR/MBC were randomized 1:1 to P + H + D or Pla + H + D, stratified by visceral v non-visceral disease and hormone receptor status. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR in pts with measurable baseline disease), OS, and safety. The target sample size (240) was determined based on the consistency threshold for PFS, defined as hazard ratio (HR) < 0.81, which maintains ≥ 50% of the risk reduction determined in CLEOPATRA (HR 0.62). Results: Two hundred forty-three pts were randomized. Baseline/disease characteristics and prior therapies were generally balanced between arms. For PFS, the HR was 0.69 (95% CI 0.49, 0.99) in the ITT population. No cases of heart failure or symptomatic left ventricular ejection fraction decline were reported. Efficacy/safety are shown in the table. Conclusions: PUFFIN met its primary endpoint. Overall, efficacy data were consistent with CLEOPATRA (ITT population and Asian subgroup). Safety was also consistent and in line with the known P safety profile, with no new or unexpected signals reported. PUFFIN adds to the totality of data with P in previously untreated HER2-positive LR/MBC, and supports the favorable benefit–risk profile of P in Chinese pts. Clinical trial information: NCT02896855. [Table: see text]

e12565 Background: Platinum-based therapy remains an effective treatment for triple-negative breast cancer (TNBC), however, the usage is largely limited due to its side effect and rapidly developed drug resistance. High prevalence of BRCA1/2 mutations are reported in TNBC. Here we explored efficacy of platinum-based regimens as the first-line treatment for Chinese patients (pts) with advanced TNBC, and analyzed its association with mutations of germline BRCA1/2 (gBRCA). Methods: We retrospectively analyze 220 patients diagnosed as advanced TNBC who were treated at the Dept. of Breast Oncology, Peking University Cancer Hospital in 2013-2018, and routinely evaluated by RECIST 1.1. Statistical analysis is performed in R 3.5.1. Cox proportional-hazard models are used for survival analysis. Results: 129 pts received non-platinum chemotherapy (NPCT) as the first-line therapy, and 91 pts received platinum-based chemotherapy (PBCT). The clinical benefit rate (CBR) and median PFS were not statistically different between NPCT and PBCT groups The median OS was 30.0 and 22.5 months for PBCT and NPCT group respectively (P = 0.09, HR = 0.70). Among them, 114 pts had BRCA gene tested, of which 14 had deleterious gBRCA mutations, 7 in each group. In PBCT group, the CBR was 85.7% and 35.1% for pts with and without deleterious gBRCA mutations respectively (P = 0.04). The median PFS, OS were 14.9 months and 5.3months (P = 0.001), 26.5 and 15.5 months (P = 0.16) for pts with and without the gBRCA mutations. No significant difference was observed between NPCT pts with and without gBRCA mutations as regards the CBR, PFS and OS. PBCT Pts had significantly more grade 3-4 anaemia (5.5% vs 0%) and thrombocytopenia (8.8% vs 0%) while higher percentage of palmar-plantar erythrodysesthesia (PPE) (12.4% vs 0%) and peripheral neuropathy (8.6% vs 1.1%) were observed in NPCT pts. Conclusions: The efficacy of platinum-based regimens as the first-line treatment of advanced TNBC insignificantly differs from that of non-platinum therapy. However, they are more effective for patients with deleterious gBRCA mutations, suggesting a BRCA1/2 genetic testing may be warranted for such patients.

e13018Background: Only a subset of patients with HER2 positive (HER2+) metastatic breast cancer (MBC) responds to anti-HER2 therapy. This study aimed at detecting plasma HER2 gene copy number (GCN)...

e24029Background: In estrogen receptor-positive breast cancer patients (pts), more than 30% have primary hormone therapy (HT) resistance while the precise mechanism underlies remain unclear. Our st...

1080Background: Circulating DNA fragments (ctDNA) are using to longitudinal non-invasive molecular monitoring and resistance mechanism interrogation of the disease by detecting genomic alteration c...

1003Background: Utidelone, a genetically engineered epothilone analog, showed excellent efficacy in phase II and III trials in terms of PFS as a primary end point and ORR as a secondary end point. ...

1105 Background: CTCs have emerged as an independent prognostic factor for metastatic breast cancer. However, the prognostic value of baseline CTCs regarding PFS in TNBC is still controversial, especially beyond first-line. We evaluated a novel combined NK cell/CTC detection system for enumeration to better understand the impact of cell count on prognosis in TNBC. Methods: 83 consecutive patients with metastatic TNBC were enrolled and received a new line of therapy (median=2, range: 1~5). Baseline circulating CTCs and NK cells were isolated and enumerated simultaneously prior to starting a new line of therapy using our previously published method targeting EpCAM (Bai et al. J Mater Chem B, 2014) and flow cytometry (antibodies against CD3-, CD45+, CD56+) respectively. The NK cell level was expressed as the proportion of total lymphocytes (%). Patients with normal to high NK cell proportion (≥ 9.15%) and > 2 CTC/2 ml were defined as NK resistant CTC, the rest were defined as non-NK resistant CTC. Results: 33 out of 83 TNBCs had first-line of therapy. Pts with ≤ 2 CTC/2 ml had a significantly longer median PFS than those with > 2 CTC/2 ml ( P = 0.028). The differences in median PFS were not significant ( P=0.110) for the entire group of pts with TNBC receiving different lines of therapy. Pts with non-NK resistant CTCs had a significantly longer median PFS than those with NK resistant CTCs ( P= 0.025), regardless of line of therapy. Conclusions: Including peripheral NK cell level into consideration can improve CTC prognostic efficiency in predicting PFS for TNBCs receiving different line of therapy. Further analysis of the unique biological features of NK-resistant CTCs and associated clinical consequence holds promise in guiding clinical practice. [Table: see text]