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PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481 ).

Background/Aims: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrenceMethods: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed.Results: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010).Conclusions: The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

Background: Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase ll trial comparing palbociclib + ET versus capecitabine in premenopausal women with hormone receptor positive, HER2 negative metastatic breast cancer (MBC). This exploratory analysis investigated potential biomarkers of palbociclib plus ET on PFS. Patients and methods: Of 178 patients randomized (92 palbociclib plus ET; 86 capecitabine), we performed targeted sequencing (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response on PFS. Hazard ratios (HRs) were estimated using unstratified Cox proportional hazards models. Results: PIK3CA (41%) and TP53 (33%) mutations and CCND1 copy number variation (29%) were found most frequently in targeted sequencing of 141 patients. ESR1 mutations were found only in 3.5% of patients of this population. Luminal type showed better prognosis in palbociclib + ET arm but no impact on PFS difference in capecitabine arm. High TMB, TP53 mutation, PTEN loss of function mutation and RB1 pathway alteration showed worse prognosis in palbociclib plus ET arm. Patients with BRCA2 pathogenic mutations showed worse prognosis regardless of PAM50 subtypes. AURKA mutation/amplification, BRIP1/MYC/RAD51C amplification were significantly associated to the patients with short PFS

Background: The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients (pts) with brain metastasis (BM) remains to be determined. Methods: A retrospective review was conducted on 77 NSCLC pts with synchronous BM who underwent first-line EGFR-TKI Tx (gefitinib: 46, erlotinib: 11, afatinib: 20). The outcomes of pts were analyzed according to the clinicopathological characteristics including local Tx modalities.Results: Fifty-nine pts underwent local Tx for BM (gamma knife surgery (GKS): 37, whole brain radiotherapy (WBRT): 18, others: 4) concurrently or sequentially with EGFR-TKI. Pts treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms (p=0.006), with a tendency toward a smaller number of BM lesions compared with those who received local treatment. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all pts were 9 and 19 months, respectively. In 60 pts with follow-up brain imaging, the median intracranial PFS was 15 months. Pts with EGFR exon 19 deletion (n=42) had a significantly longer median OS than those with L858R mutation (n=25) or other mutations (n=10) (23 vs. 17 months, p=0.010). Other clinical characteristics, including CNS symptoms (p=0.410), number of BM (p=0.709), and the use of local Tx (p=0.834), were not associated with OS, as well as PFS. In terms of the local optimal treatment modality, no difference was found between GKS and WBRT in the OS and PFS.Conclusions: This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC pts with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Pts with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.

Central venous catheters (CVCs) are generally required for chemotherapy in patients with acute leukemia, but catheter-related infection is one of the common causes of neutropenic fever. We investigated the in-hospital mortality according to early removal of CVCs and the factors influencing the mortality in patients with acute leukemia undergoing remission induction chemotherapy. This study retrospectively analyzed the hospital record data of 278 patients with acute leukemia treated with non-tunneled CVCs and remission induction chemotherapy in a single institution. Bloodstream infection was more common (p

The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified.This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25.In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5%This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).

Introduction: Many oncologists began to make sense, that the Karyopherin a-2 (KPNA2), a nucleocytoplasmic transport protein, regulates the nuclear import of macromolecules and changes in cellular phenotype. In particular, it can be a poor prognostic marker by causing aberrant subcellular localization of DNA damage response proteins or OCT4-c MYC pathway molecules depending on the type of carcinoma. An association with the p53 oncogenic pathway has been reported, showing good prognostic values in other types. We aimed to investigate the clinical significance and metabolic pathway of stable CAF and cancer cells for KPNA2 Method: We retrospectively analyzed the data from NSCLC patients receiving curative resection in Uijeongbu and Bucheon St. Mary’s Hospitals (n=165). IHC staining was performed on the tumor microarray samples using antibodies against KPNA2. The positivity was defined as median value of H-score. Result: Based on the TMA staining, mean KPNA2 score was 36.5 [0-240] and median value was 10. Table 1. Scatter plots and correlation between KPNA2 expression levels and tumor invasiveness markers reveals that high KPNA2 expressor was related to lymphatic invasion (p = 0.00782), advanced stage (p = 0.0202) and current smoker (p = 0.0074). KPNA2 expression was higher in squamous cell carcinoma(SqCC) histotype than in adenocarcinoma (SqCC ratio (%), 13.5 vs 43.4 in Low exp vs High exp; p = 0.007). Patients with high expression of KPNA2 showed shorter survival than other patients (median OS (mo), 72.8 vs 42.2, P < 0.0001; median RFS (mo), 72.8 vs 32.1, P < 0.0011) and relevant to high recurrence (recurrence rate (%), 24.7 vs 44.7, p = 0.007). Conclusion: Taken together, our results suggest that KPNA2 protein expression has a poor prognostic association, revealed by its association with survival outcome or invasiveness markers. Its clinical significance as an oncogenic target molecule is emerging, and further evaluation using an organoid model is in progress. Baseline clinical and pathological characteristics Citation Format: Seoree Kim, Heejin Lee, Jung-Sook Yoon, Hyun Woo Lee, Seok Yun Kang, Ji Hyun Lee, Sang Hoon Chun, Hye Sung Won, Soon Auck Hong, Keunsoo Kang, Young-Ho Ahn, Yoon Ho Ko. Identification and characterization of Karyopherin α2 (KPNA2), a member of the nucleocytoplasmic transporter family, in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2165.

Background: Young-PEARL study showed median progression-free survival (PFS) of 20·1 months in the palbociclib plus endocrine therapy group versus 14·4 months in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], log-rank p=0·0235). We conducted exploratory biomarker analysis to predict the efficacy of the trial. Methods: This was a phase II trial that randomized 184 patients with HR+ MBC in premenopausal women to palbociclib plus exemestane with GNRH agonist (Arm A, n=79) versus capecitabine (Arm B, n=62). We performed targeted sequencing (CancerSCANTM) containing 375 cancer-related genes (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response in terms of PFS. Result: By research-based PAM50 subtyping, 73% of patients classified as Luminal (Luminal A and Luminal B), and showed better prognosis in all patients and Arm A (p Conclusions: The alteration of a few genes including Rb1 loss may be associated with resistance of palbociclib in HR-positive premenopausal population with MBC. Luminal type showed better prognosis, and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. ESR1 mutation was found in low population frequency because all patients didn’t received AI therapy. Further exploration of molecular variables is warranted to determine and validate biomarkers of efficacy. Clinical trial information: NCT02592746. Citation Format: Kyunghee Park, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Woong-Yang Park, Seock-Ah Im, Yeon Hee Park. Exploratory biomarker analysis of Young-PEARL [palbociclib plus exemestane with GnRH agonist versus capecitabine in premenopausal women with HR (hormone receptor)-positive, HER2-negative metastatic breast cancer (MBC)] study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-19.

Background One-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service. Methods A total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy. Results The five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74–4.40, P P P P P P P P Conclusions Reducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.

Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.

BACKGROUND In the Phase II NeoSphere study (NCT00545688), dual HER2 blockade with pertuzumab (P) + trastuzumab (H), + docetaxel (D) significantly increased pathologic complete response (pCR) vs. H+D in the neoadjuvant setting for HER2-positive early breast cancer (EBC), locally advanced (LA) BC, or inflammatory BC, with supportive progression- and disease-free survival (DFS) data. Consistently, the randomized, multicenter, double-blind, placebo (Pla)-controlled Phase III PEONY trial (NCT02586025) significantly improved total pCR (tpCR; primary endpoint) with P+H+D vs. H+D in an Asian population, and safety data were in-line with the known P safety profile. We present the final analysis of long-term efficacy (at 3 and 5 years) and safety from the study. METHODS Patients had centrally confirmed HER2-positive EBC (T2–3, N0–1) or LABC (T2–3, N2 or N3; T4, any N) and were randomized 2:1 to four neoadjuvant P+H+D or Pla+H+D cycles every 3 weeks. P: 840 mg loading/420 mg maintenance doses (or Pla); H: 8 mg/kg loading/6 mg/kg maintenance; D: 75 mg/m2. Patients then received three fluorouracil, epirubicin, and cyclophosphamide cycles, followed by 13 of P+H or Pla+H in the adjuvant setting for up to 1 year. Long-term outcomes (event-free survival [EFS], DFS, overall survival [OS]; all secondary endpoints) were assessed by Kaplan–Meier methods, Cox proportional hazards models, and a two-sided log-rank test (stratified by disease category and hormone receptor status). RESULTS Data cut-off was Mar 14, 2022, and 329 patients were randomized; 219 to P; 110, to Pla. Safety populations were 218 and 110 patients, respectively. Baseline characteristics were well balanced. Most patients received the full HER2-targeted cycles. Median follow-up was 62.9 months. Long-term efficacy data are shown in the table. During the overall treatment period, 70.6% of patients in the P+H+D arm and 68.2% in the Pla+H+D arm experienced grade ≥3 adverse events (AEs); the most common (in ≥5% of patients in either arm) being neutropenia (59.2% vs. 55.5%), leukopenia (34.4% vs. 34.5%), and febrile neutropenia (5.0% vs. 3.6%). Of the most common any-grade AEs (in ≥30% of patients in either arm), diarrhea was more common in the P+H+D arm (40.8% vs. 17.3% in the Pla+H+D arm). Serious AEs were reported in 17.0% and 13.6% of patients, respectively. No primary cardiac events (heart failure [New York Heart Association grade III or IV] or significant decline of left ventricular ejection fraction) or secondary cardiac events occurred during any study periods. CONCLUSIONS Long-term efficacy endpoints (EFS, DFS, and OS) were supportive of the primary endpoint results (tpCR) and suggested a clinically meaningful improvement with P+H vs. Pla+H when administered before and after surgery for one year of anti-HER2- therapy. Safety data were in-line with the known P safety profile and generally comparable between arms, with the exception of diarrhea. PEONY adds to the totality of data showing the benefit of the P+H+D regimen in HER2-positive EBC. Table 1: Long-term efficacy data Citation Format: Zhi-Ming Shao, Da Pang, Hongjian Yang, Wei Li, Shusen Wang, Shude Cui, Ning Liao, Yong-Sheng Wang, Chuan Wang, Yuan-Ching Chang, Hwei-Chung Wang, Seok Yun Kang, Jae Hong Seo, Kunwei Shen, Suphawat Laohawiriyakamol, Zefei Jiang, Liang Huang, Haiyan Wang, François Lamour, Grace Song, Eleonora Restuccia. Final analysis of the Phase III PEONY trial: long-term efficacy and safety of neoadjuvant–adjuvant pertuzumab or placebo, plus trastuzumab and docetaxel, in patients with HER2-positive early or locally advanced breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-03.

B-RafV600E oncogene mutation occurs in various cancers and is associated with tumor initiation. However, genetic modification of B-RafV600E in cells induces MAPK activation and results in oncogene-induced senescence. Overcoming the oncogene-induced senescence by B-RafV600E requires activation of another oncogene pathway, such as AKT signaling. In the present study, we explored the factors involved in overcoming the senescence program in cells activated by B-RafV600E and AKT signaling. B-RafV600E activation caused a feedback inhibition of AKT phosphorylation and resulted in downregulation of FoxM1, one of the AKT downstream components. AKT activation by PTEN downregulation induced FoxM1 expression, and co-expression of B-RafV600E and FoxM1 overcame the cellular senescence. These observations suggested that FoxM1 is critical downstream gene of AKT and functions to overcome B-RafV600E-induced senescence.

Purpose We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. Materials and Methods Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. Results Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. Conclusion Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Pure mucinous breast carcinoma (PMBC) is characterized by clusters of tumor cells floating in abundant extracellular mucin and can be classified into paucicellular (Type A) and hypercellular (Type B) subtypes. However, the clinicopathological and genomic differences between these two subtypes have not been well characterized. We retrospectively investigated the clinicopathologic features of 45 cases of surgically removed PMBC (31 Type A and 14 Type B). We also performed whole-exome sequencing (WES) in eight cases of PMBC. We found that Type B PMBC occurs at an older age and shows more aggressive clinical behavior than Type A. WES analysis revealed that HYDIN was the most frequently mutated gene in both types of PMBC. Although Type B PMBC showed a tendency toward more frequent genetic alterations, there were no statistically significant differences between the two subtypes in single nucleotide variants or insertions or deletions of bases associated with moderate or high effects. Our results provide additional evidence that PMBCs are clinicopathologically and genetically heterogeneous and lack pathognomonic genetic alterations. Further, Type B PMBC is more frequently associated with lymph node metastasis than Type A.

Advanced breast cancer frequently metastasizes to the skeleton causing major mobility issues and hazards to quality of life. To manage osteolytic bone metastasis, bone-modifying agents and chemotherapy are recommended as the standard of care. Here, we investigated serologic biomarkers that might be associated with prognosis in breast cancer patients treated with zoledronic acid (ZA) and taxane-based chemotherapy. We collected serum samples from breast cancer patients with bone metastasis who received taxane plus ZA as palliative treatment. Fourteen biomarkers of angiogenesis, immunogenicity, and apoptosis were assessed, and the correlation between serum cytokine levels and patient's prognosis was statistically analyzed. Sixty-six patients were enrolled, and samples from 40 patients were analyzed after laboratory quality control. Patients with low baseline PDGF-AA, high IFN-γ, low MCP-2, low TGF-β1, and low TNF-α were significantly associated with longer progression-free survival (PFS). Decreasing VEGF and TNF-α and increasing FGF-2 and PDGF-AA in the early treatment phase indicated longer PFS. In univariate and multivariate analyses, low TGF-β1 and TNF-α and high IFN-γ at baseline were associated with a significantly low hazard ratio for disease progression. Further, we designed a risk score with TGF-β1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-β1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.

BACKGROUND Accurate and rapid clinical decisions based on real-world evidence are essential for patients with cancer. However, the complexity of chemotherapy regimens for cancer impedes retrospective research that uses observational health databases. OBJECTIVE The aim of this study is to compare the anticancer treatment trajectories and patterns of clinical events according to regimen type using the chemotherapy episodes determined by an algorithm. METHODS We developed an algorithm to extract the regimen-level abstracted chemotherapy episodes from medication records in a conventional Observational Medical Outcomes Partnership (OMOP) common data model (CDM) database. The algorithm was validated on the Ajou University School Of Medicine (AUSOM) database by manual review of clinical notes. Using the algorithm, we extracted episodes of chemotherapy from patients in the EHR database and the claims database. We also developed an application software for visualizing the chemotherapy treatment patterns based on the treatment episodes in the OMOP-CDM database. Using this software, we generated the trends in the types of regimen used in the institutions, the patterns of the iterative chemotherapy use, and the trajectories of cancer treatment in two EHR-based OMOP-CDM databases. As a pilot study, the time of onset of chemotherapy-induced neutropenia according to regimen was measured using the AUSOM database. The anticancer treatment trajectories for patients with COVID-19 were also visualized based on the nationwide claims database. RESULTS We generated 178,360 treatment episodes for patients with colorectal, breast, and lung cancer for 85 different regimens. The algorithm precisely identified the type of chemotherapy regimen in 400 patients (average positive predictive value >98%). The trends in the use of routine clinical chemotherapy regimens from 2008-2018 were identified for 8236 patients. For a total of 12 regimens (those administered to the largest proportion of patients), the number of repeated treatments was concordant with the protocols for standard chemotherapy regimens for certain cases. In addition, the anticancer treatment trajectories for 8315 patients were shown, including 62 patients with COVID-19. A comparative analysis of neutropenia showed that its onset in colorectal cancer regimens tended to cluster between days 9-15, whereas it tended to cluster between days 2-8 for certain regimens for breast cancer or lung cancer. CONCLUSIONS We propose a method for generating chemotherapy episodes for introduction into the oncology extension module of the OMOP-CDM databases. These proof-of-concept studies demonstrated the usability, scalability, and interoperability of the proposed framework through a distributed research network.

Background Although combination chemotherapy (CC) is generally recommended in recurrent or primary metastatic gastric cancer (RPMGC), the results of randomized trials are conflicting. Methods A retrospective review was conducted on 687 RPMGC patients who received palliative chemotherapy. We compared the overall survival (OS) between CC and single-agent chemotherapy (SC) among these patients, and we analyzed the clinicopathological characteristics affecting outcome including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Results Although 521 patients (75.8%) underwent CC, SC was more frequently performed in elderly patients (57.6%) and ECOG performance status (PS) 2 or 3 (65.8%) patients (p p p = 0.583), poor PS (p = 0.810), signet ring cell (p = 0.347), palliative surgical resection (p = 0.307), and high PLR (p = 0.120), with a significant interaction between age and type of regimen (p = 0.012). Moreover, there was no difference in OS between CC and SC after propensity score matching (p = 0.322). Multivariate analysis revealed that palliative resection and ≥ second-line chemotherapy were independently associated with favorable OS (p p = 0.004), signet ring cell (p p = 0.04), high NLR (p = 0.001), and high PLR (p = 0.033) were independent prognostic factors of poor OS. Conclusions Although CC is the standard of care in RPMGC, SC can be considered a reasonable option in certain subgroups, such as elderly patients.

Background Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 − 11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov NCT01839773.

Exon 19 deletion and L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are both common mutations that predict a good response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the existence of clinically significant difference in sensitivity to EGFR tyrosine kinase inhibitors among different EGFR mutation subtypes is still a matter of debate.The outcome of 60 EGFR mutation-positive advanced NSCLC patients who received first-line gefitinib therapy (250 mg/d) was retrospectively analyzed according to EGFR mutation subtypes.The median progression-free survival (PFS) and overall survival (OS) after the initiation of gefitinib therapy for all patients was 11 and 26 months, respectively. Univariate analysis showed that patients with exon 19 deletion (n=28) had significantly longer median PFS (20 vs. 8 mo, P=0.004) and OS (36 vs. 22 mo, P=0.001) compared with those with L858R mutation (n=25) and uncommon or dual mutations (n=7). Multivariate analysis revealed that exon 19 deletion (P=0.007) was an independent prognostic factor of favorable PFS, with an independent association with poor PFS of male sex (P=0.049). Exon 19 deletion was also independently associated with favorable OS (P0.0001), whereas male sex (P=0.004) and primary metastatic disease (P=0.032) were independent prognostic factors of poor OS.The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.

The predictive significance of osteolysis-related proteins was evaluated in bortezomib-treated multiple myeloma. The clinicopathological characteristics were collected retrospectively. Immunohistochemistry was performed for analyzing receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), macrophage inflammatory protein 1 alpha (MIP1α), and dickkopf-1 (DKK1) expression. Among clinicopatholgical characteristics, osteolytic lesion was associated with higher response to bortezomib treatment (79% vs. 46%). High DKK1 expression was significantly correlated with osteolytic lesion (

Purpose Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients. Methods This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP. Results The prevalence of NCP was associated with age 6 months (OR, 1.57; 95% CI, 1.232–2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593–0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225–2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671–2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p Conclusion Age 6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.

The treatment of metastatic breast cancer depends on the patient`s condition, site of metastasis, and molecular subtype of cancer. Hormone receptor-positive patients, which account for 60-70% of all breast cancer patients, have the advantage of having an effective, less-toxic, hormone therapy treatment. Hormone therapy should be used actively because it is very useful in terms of the patient`s quality of life, by increasing the response rate and delaying the progression of cancer. Recently, studies have examined the mechanism of resistance to hormone therapy. We need to combine various target therapies to overcome resistance. The development of therapeutic agents based on molecular biological characteristics should help to improve the survival of patients with metastatic breast cancer. (Korean J Med 2017;92:251-258)

Purpose The effects of biological subtypes within breast cancer on prognosis are influenced by age at diagnosis. We investigated the association of young age with locoregional recurrence (LRR) between patients with luminal subtypes versus those with nonluminal subtypes. Materials and Methods Medical records of 524 breast cancer patients with positive lymph nodes between 1999 and 2010 were reviewed retrospectively. All patients received curative surgery and adjuvant chemotherapy based on contemporary guidelines. Radiation was delivered for patients who underwent breast conserving surgery or those who had four or more positive lymph nodes after mastectomy. Adjuvant hormone therapy was administered to 413 patients with positive hormone receptors according to their menstrual status. Results During median follow-up of 84 months, the 10-year locoregional recurrence-free survival rate (LRRFS) was 84.3% for all patients. Patients < 40 years showed significantly worse 10-year LRRFS than those ≥ 40 years (73.2% vs. 89.0%, respectively; p=0.01). The negative effect of young age on LRRFS was only observed in luminal subtypes (69.7% for < 40 years vs. 90.8% for ≥ 40 years; p < 0.01). Multivariate analysis using luminal subtypes ≥ 40 years as a reference revealed luminal subtypes < 40 years were significantly associated with increased risk of LRR (hazard ratio, 2.33; p < 0.01). Conclusion Young breast cancer patients with positive lymph nodes had a higher risk of LRR than those aged ≥ 40 years. This detrimental effect of young age on LRR was confined in luminal subtypes.

Purpose Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC), who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials. Materials and methods In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2 dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease. Results A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively. Conclusion This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

Importance Prospective assessment of treatments known to benefit patients in global clinical trials in specific racial groups is essential. Objective To compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer. Design, Setting, and Participants This multicenter, double-blind, placebo-controlled phase 3 trial enrolled 329 women with ERBB2-positive early (T2-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) and primary tumor larger than 2 cm from March 14, 2016, to March 13, 2017. Analysis of the primary end point was performed on an intention-to-treat basis. Interventions Before surgery, patients received 4 cycles of intravenous pertuzumab (840-mg loading dose and 420-mg maintenance doses), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), and docetaxel (75 mg/m2) or intravenous placebo, trastuzumab, and docetaxel every 3 weeks. After surgery, patients received 3 cycles of intravenous fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of the same intravenous anti-ERBB2 therapy (pertuzumab and trastuzumab or placebo and trastuzumab) for up to 1 year. Main Outcomes and Measures The primary end point was independent review committee–assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by disease category and hormone receptor status, was used to compare rates between treatment groups. Results In total, 329 female patients were randomized (pertuzumab, 219; and placebo, 110; mean [SD] age, 48.8 [9.5] years). In the intention-to-treat population, total pathologic complete response rates were 39.3% (86 of 219) in the pertuzumab group and 21.8% (24 of 110) in the placebo group (difference, 17.5% [95% CI, 6.9%-28.0%];P = .001). Of the most common grade 3 or higher adverse events, there was a higher incidence of neutropenia in the pertuzumab group (83 of 218 [38.1%] vs 36 of 110 [32.7%]). Serious adverse events were reported in 10.1% of patients (22 of 218) in the pertuzumab group and 8.2% of patients (9 of 110) in the placebo group. Conclusions and Relevance Treatment with pertuzumab, trastuzumab, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trastuzumab, and docetaxel for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients. Safety data were in line with the known pertuzumab safety profile and generally comparable between treatment groups. The PEONY trial adds to the totality of data showing the benefit of the pertuzumab regimen. Trial Registration ClinicalTrials.gov identifier:NCT02586025

Summary Background Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0–2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov , NCT02592746 , and is ongoing for follow-up of overall survival. Findings Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9–22), median progression-free survival was 20·1 months (95% CI 14·2–21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1–17·0) in the capecitabine group (hazard ratio 0·659 [95% CI 0·437–0·994], one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 [75%] of 92 vs 14 [16%] of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred. Interpretation Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen. Funding Pfizer, Shinpoong, and Daewoong Korea and Takeda.

B-Raf

The role of palliative surgical resection in recurrent or metastatic gastric cancer is still controversial. A retrospective review was conducted on 689 patients who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 382) gastric cancer. Among 131 patients (89 primary metastatic and 42 recurrent) with surgical resection before chemotherpay, 75 underwent gastrectomy, 42 metastasectomy, and 14 gastrectomy with metastasectomy. The median overall survival (OS) of patients who underwent surgical resection was significantly longer than that of patients who received chemotherapy alone (18 vs. 9 months, p p p p pensity score matching. In addition, the median OS of patients who underwent gross complete resection (n = 54) was significantly longer than that of patients who underwent incomplete resection (n = 77) (30 vs. 15 months, p = 0.002). The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer patients may result in a favorable outcome, especially when complete resection is achievable.

To compare the incidence of brain metastases of advanced non-small cell lung cancer (NSCLC) treated with systemic cytotoxic chemotherapy (CC) and targeted therapy (TT), we performed a large-scale, retrospective, nationwide, cohort study. The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011, to November 30, 2016. Of the 29,174 patients newly diagnosed with stage IIIB or IV NSCLC who received systemic treatment, we investigated the initial and subsequent incidence of brain metastases. Besides, among 22,458 patients without initial brain metastasis, the overall cumulative incidence of subsequent brain metastases was compared according to systemic treatment administered. In total, 1,126 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7% vs. 3.8%; 3-year: 17.2% vs. 5.0%; P

Background: Endocrine treatment is preferred recommendation by clinical guidelines in premenopausal as well as postmenopausal women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). In real-world clinical practice, however, substantial numbers of patients are treated with chemotherapy in earlier lines The purpose of this phase II study was to compare the clinical antitumor activity and safety of combined therapy with exemestane plus gonadotropin-releasing hormone (GnRH) agonist plus palbociclib with that of capecitabine in premenopausal women with HR-positive, HER2-negative MBC. Methods: This was a prospective, two-arm, randomized, multicenter open-label phase II study. Participants were premenopausal women with breast cancer that had relapsed or progressed during prior tamoxifen. One line of previous chemotherapy for metastatic setting was allowed. Patients were randomized to chemotherapy (capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks) or combination endocrine therapy (exemestane 25 mg/day for 28 days and palbociclib 125 mg/day for 21 days every 4 weeks plus leuprolide). Primary end point was progression-free survival (PFS). Findings: Of 189 patients enrolled between 2015 and 2018 from 14 centers, 184 were randomly assigned to chemotherapy (n=92) or endocrine therapy with palbociclib (n=92). Median age was 44 years (range 28–58). Approximately half the patients (51%) were treatment naive for MBC. During a median 17 months of followup, median PFS was superior for endocrine therapy plus palbociclib than for capecitabine [20·1 vs. 14·4 months, p=0·0469 by log-rank test; hazard ratio 0·659 (95 CI 0·437–0·994)]. Hematological toxicities of ≥ grade 3 were significantly more common with palbociclib than with capecitabine (75·0% vs. 16·3%). Diarrhea (12·0% vs. 38·4%) and hand–foot syndrome (1% vs. 77%) were more common with capecitabine. Interpretation: Exemestane plus palbociclib with ovarian suppression showed clinical benefit in terms of PFS compared with capecitabine in premenopausal patients with HR-positive, HER2-negative MBC. Trial Registration: The ClinicalTrials.gov identifier number was NCT02592746. Funding Statement: This study was supported by Pfizer (exemestane, palbociclib), Shinpoong (capecitabine), Daewoong Korea and Takeda (leuprolide) for study drugs. This work was partly funded by a grant from the Ministry of Health and Welfare, Republic of Korea (HA17C0055) and by the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1720150). Declaration of Interests: Dr. PARK reports grants and non-financial support from Pfizer, grants and non-financial support from AstraZeneca, grants and non-financial support from Novartis, grants and non-financial support from Merck, grants from Eisai, grants and non-financial support from Roche, outside the submitted work. Dr. Im reports grants from Pfizer, drug supply from Pfizer, Shinpoong, Daewoong, and Dakeda, during the conduct of the study; grants from AstraZeneca and Pfizer, travel expenses for advisory board participation and advisory role for Novartis, advisory role for Hanmi, Pfizer, Eisai, Amgen, Lilly, MediPacto, Roche, outside the submitted work. Dr. Jung reports personal fees from AstraZeneca Korea, personal fees from Roche Korea, outside the submitted work. Dr. Kim reports grants from Ono Pharma Korea Co., Ltd., outside the submitted work. Dr. Ahn reports personal fees and non-financial support from Astrazeneca, Roche, Beringer Ingelheim, Menarini, Pfizer, BMS, ONO, Boryung, grants from Samyang, outside the submitted work. Dr. Lee reports personal fees from AstraZeneca, personal fees from Bayer, personal fees from Eisai, personal fees from Novartis, personal fees from Ono, personal fees from Roche, personal fees from Samsung Bioepis, outside the submitted work. Dr. Kim reports grants from Novarts, grants from Sanofi Genzyme, non-financial support from Dongkook Pharma Co Ltd., outside the submitted work. Dr. Ahn reports personal fees from Amgen, personal fees from Pfizer, personal fees from AstraZeneca, personal fees from Menarini, personal fees from Roche, personal fees from Eisai, personal fees from Boehringer-Ingelheim, personal fees from BMS-Ono, personal fees from MSD, personal fees from Janssen, personal fees from Samsung Bioepis, personal fees from Takeda, outside the submitted work. All other authors declare they have no conflicts of interest. Ethics Approval Statement: The study was conducted in full accordance with the guidelines for Good Clinical Practice and the Declaration of Helsinki, and was approved by the institutional ethics committees of each hospital and the KCSG institutional review board. Written informed consent was obtained from each participant.

Background:Standard intravenous (IV) paclitaxel is associated with hypersensitivity/toxicity. Alternative IV formulations have improved tolerability but still require frequent hospital visits and IV infusion. DHP107 is a novel oral formulation of paclitaxel that is approved in South Korea for the treatment of gastric cancer.Methods:This multicenter, phase II study using a Simon’s two-stage design investigated the efficacy and safety of DHP107 200 mg/m2administered orally twice daily on days 1, 8, and 15 every 4 weeks for the first-line treatment of recurrent or metastatic HER2-negative breast cancer.Results:Thirty-six patients were enrolled and 31 were assessable for efficacy. Patient median age was 57 years (range = 34–81) and 11 (31%) had triple-negative disease. A median of seven cycles (range = 1–28) of DHP107 was administered. Objective response rate was 55% (17 patients), all partial responses, according to the investigator’s decision and independent central review (ICR), and 44% (4/9 patients) in those with triple-negative disease. Disease control rate (partial response and stable disease) was 74% (23 patients) according to the investigator’s decision and ICR. In the intention-to-treat (ITT) population of all enrolled participants, the objective response rate was 50% (18/36 patients). Median progression-free survival was 8.9 months [95% confidence interval [CI]: 5.2–12.3) and median time to treatment failure was 8.0 months (95% CI: 4.2–10.0). DHP107 had an acceptable toxicity profile. All patients experienced treatment-emergent adverse events; the most common adverse events were decreased neutrophil count (81% all grades and 78% grade ⩾ 3) followed by peripheral sensory neuropathy (61% all grades and 8% grade 3). However, there was no febrile neutropenia or sepsis.Conclusion:DHP107 showed promising efficacy and acceptable tolerability in this phase II study and is currently being investigated in the OPTIMAL phase III study (NCT03315364).Trial registration:This trial was registered with ClinicalTrials.gov identifier: NCT03315364.

This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 μg/m2/day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = −0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm3 and 161.75/mm3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.

Purpose We evaluated the prevalence and characteristics of breakthrough cancer pain (BTcP) in Korean patients admitted with cancer pain. Materials and Methods In-hospital patients with cancer pain completed a questionnaire concerning severity of background cancer pain (BCP), prevalence and treatment for BTcP, sleep disorders, and satisfaction with cancer pain treatment. Medical records showing medications for BCP and BTcP were also evaluated. Results Total 609 patients with controlled BCP enrolled. Mean age of the patients was 59.5 years old, and 59% were male. Of all patients, 177 (29%) complained of BTcP. No clinical characteristic predicted BTcP. Of the 177 patients with BTcP, 56% did not receive treatment for BTcP. Patients with BTcP showed significant association with a sleep disorder and dissatisfaction with pain control, compared to those without BTcP (p < 0.0001 and p=0.0498, respectively). Oxycodone-immediate release was the most commonly used short-acting analgesic, followed by intravenous morphine. Conclusion The prevalence of BTcP was 29% in patients admitted with controlled BCP. Although the patients had well-controlled BCP, BTcP showed association with a lower quality of life in patients with cancer. More medical attention is needed for detection and management of BTcP.

Objectives Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their synergistic activity in combination, we conducted a phase II study to determine the clinical activity of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC). Materials and methods Patients with advanced NSCLC who have received one or two prior chemotherapy regimens for metastatic disease, ECOG 0–2, and adequate organ function were eligible. Patients received 400mg twice daily sorafenib and 150mg daily erlotinib in 28-day cycles. Epidermal growth factor receptor mutation and its downstream pathways were analyzed from available tumor samples. Changes in plasma cytokine and angiogenic factors were correlated with clinical outcomes. Results A total of 46 patients were enrolled. Twenty patients (43%) were never smokers and 35 patients (75%) had adenocarcinoma histology. The overall response rate was 30.4%. Response to sorafenib/erlotinib was observed more commonly in patients with EGFR mutation than in those with EGFR wild type (WT) or EGFR unknown tumors (62.5% vs. 6.7% vs . 34.8%; P = 0.013). Likewise, DCR was higher among patients with EGFR mutation than in those with EGFR WT or EGFR unknown tumors (87.5% vs. 46.7% vs. 60.9%; P =0.161). The most frequent adverse events (AEs) of all grades were hand-foot skin reaction (67.4%) followed by acneiform rash (58.7%). Conclusion Sorafenib combined with erlotinib is well-tolerated with manageable toxicity and appears to be effective against advanced NSCLC with one or two prior line of systemic treatment (NCT00801385).

In the era of CDK4/6 inhibitors in hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, few trials have been specifically studied to compare quality of life between palbociclib plus endocrine therapy (ET) and cytotoxic chemotherapy exclusively in premenopausal women. We aimed to evaluate differences of patient report outcomes (PROs) between palbociclib plus ET and capecitabine. PROs were assessed using EORTC QLQ-C30 at baseline, every 6 weeks, and the end of treatment. All EORTC QLQ-30 scores were maintained from baseline to the end of treatment. Patients treated palbociclib plus ET arm experienced delay in time-to-deterioration of physical functioning (HR = 0.58, 95% CI, 0.36 to 0.84, p = 0.0058), nausea and vomiting (HR = 0.48, 95% CI, 0.32 to 0.73, p = 0.0005), and diarrhea (HR = 0.42, 95% CI, 0.27 to 0.65, p = 0.001). There was a numeric trend for worsening of insomnia (HR = 1.43, 95% CI, 0.96 to 2.16, p = 0.079) and favoring of appetite loss (HR = 0.69, 95% CI, 0.44 to 1.07, p = 0.09) in the palbociclib plus ET arm. Premenopausal patients with palbociclib plus ET maintained QoL without compromising treatment efficacy.

The prognostic significance of Bcl-2, Bcl-6, p53, topoisomerase II, and β-tubulin expression was evaluated in diffuse large B-cell lymphoma (DLBCL) patients treated with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab. Eight-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.001) of patients with high Bcl-2 expression were significantly inferior to those of patients with low expression without prognostic significance of Bcl-6, p53, topoisomerase II, and β-tubulin expression. High expression of Bcl-2 was associated with poor PFS (P = 0.045) and OS (P = 0.004) only in patients with low international prognostic index (IPI). In multivariate analysis, high expression of Bcl-2 was a significant independent prognostic factor of poor PFS (P = 0.026) and OS (P = 0.007) along with high IPI. In conclusion, the expression of Bcl-2 may be a useful prognostic factor, especially in DLBCL patients with low IPI.

Background Trastuzumab has been approved for use in combination with fluoropyrimidine plus cisplatin for the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). Although capecitabine plus oxaliplatin (XELOX) is a standard first-line regimen for AGC, combination trastuzumab plus XELOX has not been studied. Methods Patients with metastatic or unresectable HER2-positive AGC were diagnosed by either HER2 immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in-situ hybridisation (FISH)+ received intravenous trastuzumab (8mg/m 2 for first cycle and 6mg/m 2 for subsequent cycles on day 1) plus oral capecitabine (1000mg/m 2 twice daily on days 1–14) and intravenous oxaliplatin (130mg/m 2 on day 1), every 3weeks. The primary end-point was the objective response rate, and secondary end-points included progression-free survival (PFS), overall survival (OS) and toxicity profiles. Results Fifty-five HER2-positive AGC patients were enrolled between August 2011 and February 2013. The median age was 57years (range=29–74). The confirmed objective response rate was 67% (95% confidence interval (CI)=54–80%). After a median follow-up period of 13.8months (range=6.1–23.9), the median PFS and OS were 9.8months (95% CI=7.0–12.6) and 21.0months (95% CI=6.4–35.7), respectively. Frequently encountered grade 3–4 toxicities included neutropenia (18%), anaemia (11%), and peripheral neuropathy (11%). There was a treatment-related death caused by severe diarrhoea and complicated sepsis. Conclusion Combination of trastuzumab and XELOX is well tolerated and highly effective in patients with HER2-positive AGC.

Background Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. Methods A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1–2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan–Meier methods. Results We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5–6.0 months) and 8.5 months (95% CI 5.6–11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. Conclusion Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

Background The P300 is a major index used to evaluate improvements in brain function. Although a few studies have reported evaluating the effectiveness of manual acupuncture or electro-acupuncture by monitoring the P300, research in this field is not yet very active. The aim of this study was to investigate the effects of periodic low-frequency electrical stimulation applied to BL62 and KI6 on brain activity by analyzing the P300. Method The study was conducted as a randomized double-blind test of 55 subjects in their 50s, including 26 males and 29 females. Each subject received 12 sessions of stimulation over a one-month period. In each session, low-frequency electrical stimulation at an average of 24 μA and 2 Hz was applied to the acupuncture points BL62 and KI6, and event-related potentials (ERPs) were measured before the first session and after the last session of the electrical stimulation. Results The results of a chi-square test indicated that the double-blind test was conducted correctly. Compared to the Sham group, all the subjects in the Real stimulation group showed a tendency toward a decreasing P300 latency and increasing P300 amplitude after all 12 sessions of stimulation. In the women, the amplitude significantly increased at Fz, Fcz, Cz, Cpz, and Pz. Conclusions With this experiment, the low-frequency electrical stimulation of two acupuncture points (BL62 and K16) was confirmed to have a positive influence on the prevention of natural cerebral aging. Trial registration This study was registered at the Clinical Research Information Service (CRIS) of the National Research Institute of Health ( https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp? , Registration Number: KCT0001940). The date of registration was June 9, 2016.

Purpose Neuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL. Methods Cancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed. Results A total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5–39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96 ± 1.94 versus 4.24 ± 2.02, p

We aimed to present the clinical outcomes of adjuvant concurrent chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct cancer (EHBDC). From October 1994 to April 2013, 41 patients received adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen patients received low-dose of cisplatin just before every delivery of radiation therapy, and 21 patients received two cycles of 5-FU-based regimen during radiotherapy. We compared the clinical outcomes between two adjuvant CCRT regimens. Adjuvant CCRT with low-dose daily cisplatin showed comparable toxicity profiles compared with that of a 5-FU-based regimen. The median follow-up time was 33 months (range, 5–205), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses showed no significant differences in OS, LRRFS, and DMFS between the groups with two regimens. In multivariable analyses, chemotherapeutic regimen was a significant prognostic factor for OS, favoring the low-dose daily cisplatin regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p = 0.642) and DMFS (p = 0.756). Adjuvant CCRT with low-dose daily cisplatin regimen showed acceptable toxicities and survivals compared to those of the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible regimens for adjuvant CCRT for EHBDC.

The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m(2) on day 1 every 3 weeks, or docetaxel 60 mg/m(2) on day 1 every 3 weeks. The primary endpoint was progression-free survival. Between November 2006 and December 2007, 81 patients were included in this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median progression-free survival was 6.8 months (95 % confidence interval [CI] = 5.4-12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 % CI = 4.0-13.7 months) in the docetaxel-alone group (hazard ratio [HR] = 1.0; 95 % CI = 0.6-1.8; p = 0.95). There were no significant differences in the overall response rates and overall survival between groups (p = 0.29 and p = 0.42, respectively). In subgroup analysis, TSU-68 plus docetaxel was associated with better overall survival than docetaxel alone in anthracycline-resistant patients (HR = 0.3; 95 % CI = 0.1-0.8; p = 0.02). The most frequent adverse events were neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity was more frequently observed in the TSU-68 plus docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated breast cancer patients. As TSU-68 was associated with better survival in the anthracycline-resistant subgroup, it should be further explored in this subgroup.

76 Background: Several systemic inflammatory markers in blood have been suggested as prognostic factors in various cancers. We investigated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) in patients (pts) with non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy. Methods: A retrospective review was conducted on 108 pts who received adjuvant chemotherapy after surgical resection of NSCLC. Disease-free survival (DFS) and overall survival (OS) of pts with high NLR and ALC ( > median value) before surgery or chemotherapy were compared to those of pts with low NLR and ALC (≤median value). Results: The number of pts at AJCC stage IB, IIA, IIB, IIIA, and IIIB were 1, 38, 9, 58, and 2, respectively. Adenocarcinoma,squamous cell carcinoma, and other histologic types were present in 66 (61.1%), 32 (29.6%), and 10 (9.3%) patients, respectively. The most frequently used chemotherapy regimen was vinorelbine/cisplatin (81 pts), followed by paclitaxel/carboplatin (22 pts), and others (5 pts). A total of 61 (56.5%) pts received adjuvant radiotherapy (before adjuvant chemotherapy: 53 pts). Preoperative NLR and ALC were not associated with clinicopathologic characteristics including stage and histologic types. High prechemotherapy NLR and low ALC were more frequently observed in pts who underwent radiotherapy before chemotherapy (p < 0.0001). The median follow-up duration was 61 (29-153) months for survivors. The longer median DFS was observed in pts with stage IB or II (65 vs. 22 months, p = 0.025) and high prechemotherapyALC (65 vs. 20 months, p = 0.036), without significant difference in OS. On the other hand, NLR and preoperative ALC were not associated with outcome of pts. Conclusions: The present study suggests that high prechemotherapyALC is associated with favorable outcome in stage IB-III NSCLC pts who received adjuvant chemotherapy after surgical resection.

1007 Background: Endocrine treatment is preferred recommendation by clinical guidelines in premenopausal as well as postmenopausal women with hormone receptor(HR)-positive, HER2-negative metastatic breast cancer(MBC). In real-world clinical practice, however, substantial numbers of patients are treated with chemotherapy in earlier lines based on endocrine resistance and/or on physician’s concern of worse prognosis associated with aggressive tumor behavior and younger age. In terms of the chemotherapy regimens, capecitabine seems one of the most popular options. The purpose of this phase II study is to assess the safety and the clinical anti-tumor activity of exemestane plus GNRH agonist in combination with palbociclib versus capecitabine in premenopausal HR-positive MBC patients. Methods: This is a prospective, two-arm, randomized, multi-center open-label phase II study of the Korean Cancer Study Group. Patients were allowed with previous 1 line of chemotherapy for MBC. De Novo metastatic patients should have been treated with tamoxifen before enrollment. Patients were randomized to chemotherapy (capecitabine 1250 ㎎/㎡twice a day from day 1 to 14 every 3 weeks) or endocrine therapy combination (exemestane 25 mg for 28 days and palbociclib 125 mg for 21 days every 4 weeks with GNRH agoinst). Primary endpoint was Progression-Free Survival (PFS). Results: Among 189 patients enrolled between 2016 and 2018 from 14 centers, 184 patients were randomly assigned to chemotherapy (n = 92) or endocrine therapy with palbociclib (n = 92). Median age was 44 (range 28-58). De Novo MBC was found equally in both arm (30%). During median 14 months of follow-up, median PFS was superior in endocrine with palbociclib than in capecitabine arm [19.0 vs. 11.3 months, p = 0.0493 by log-rank test; Hazard Ratio (HR) 0.643 (0.415-0.999), p = 0.0493]. Approximately half of the patients (51%) were treatment naïve in the advanced setting (49% for palbociclib vs. 51% for capecitabine). Grade III or more hematologic toxicities were more common in palbociclib than in capecitabine with statistical significance (60.9% vs. 19.2%, p < 0.0001). Diarrhea (11% vs. 38%) and Hand-Foot syndromes (1% vs. 76%) were more common in capecitabine arm. Conclusions: Exemestane plus palbociclib with ovarian suppression showed clinical benefit in terms of PFS compared with capecitabine in patients with premenopausal ER-positive MBC. Clinical trial information: NCT02592746.

e20002 Background: Several systemic inflammatory markers in blood have been suggested as prognostic factors in various cancers. We investigated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) in patients (pts) with non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy. Methods: A retrospective review was conducted on 108 pts who received adjuvant chemotherapy after surgical resection of NSCLC. Disease-free survival (DFS) and overall survival (OS) of pts with high NLR and ALC ( > median value) before surgery or chemotherapy were compared to those of pts with low NLR and ALC (≤median value). Results: The number of pts at AJCC stage IB, IIA, IIB, IIIA, and IIIB were 1, 38, 9, 58, and 2, respectively. Adenocarcinoma, squamous cell carcinoma, and other histologic types were present in 66 (61.1%), 32 (29.6%), and 10 (9.3%) pts, respectively. The most frequently used chemotherapy regimen was vinorelbine/cisplatin (81 pts), followed by paclitaxel/carboplatin (22 pts), and others (5 pts). A total of 61 (56.5%) pts received adjuvant radiotherapy (before adjuvant chemotherapy: 53 pts). Preoperative NLR and ALC were not associated with clinicopathologic characteristics including stage and histologic types. High prechemotherapy NLR and low ALC were more frequently observed in pts who underwent radiotherapy before chemotherapy (p < 0.0001). The median follow-up duration was 70 (38-162) months for survivors. Pts with stage III demonstrated poor DFS (p = 0.019) and OS (p = 0.028) compared to those with stage IB or II. The shorter median DFS was observed in pts with low prechemotherapy ALC (20 vs. 65 months, p = 0.021), without significant difference in OS (p = 0.088). On the other hand, NLR and preoperative ALC were not associated with outcome of pts. Conclusions: The present study suggests that high prechemotherapy ALC is associated with poor outcome in stage IB-III NSCLC pts who received adjuvant chemotherapy after surgical resection.

e20572 Background: We performed a large-scale, retrospective, nationwide, cohort study of the incidence of brain metastasis in patients with advanced non-small-cell lung cancer (NSCLC) according to the systemic treatment administered. Methods: The data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011 to November 30, 2016. Of the 29,224 patients newly diagnosed with stage IIIB or IV NSCLC who received first-line cytotoxic chemotherapy (CC group) or targeted therapy (TT group), 22,508 patients without brain metastasis were analyzed. Results: In total, 1,131 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7 ± 0.6% vs. 3.8 ± 0.3%; 3-year: 17.2 ± 0.7% vs. 5.0 ± 0.3%, respectively; P < 0.001), despite the higher rate of brain metastasis in the CC group at < 3 years after diagnosis. Younger age, female sex, living in a rural area, anticoagulant use, and first-line TT (relative risk, 2.17 ± 0.03; 95% confidence interval, 1.92–2.50, P < 0.0001) retained significant associations with subsequent brain metastasis after adjusting for all variables. Conclusions: In the Korean population, the overall cumulative incidence of brain metastasis was significantly higher in patients in the TT group than in those in the CC group; the former could be regarded as having mutations in the EGFR or ALK gene.

e20616 Background: More than one third of advanced non-small cell lung cancer (NSCLC) patients (pts) experience brain metastases in the course of their disease. Although the outcome of NSCLC pts with brain metastasis is generally poor, identifying subgroups of pts that could benefit from appropriate therapeutic approach is clinically important, particularly in EGFR tyrosine kinase inhibitor (TKI) era. Methods: A retrospective review was conducted on 85 NSCLC pts with synchronous brain metastasis who underwent at least first-line chemotherapy, after treatment (Tx) for brain metastasis (gamma knife surgery or fractionated stereotactic radiotherapy : 42, whole brain radiation therapy : 38, surgical resection : 1, and no Tx : 4) from Jan 2002 to Dec 2013. Overall survival (OS) of all pts was analyzed according to the clinicopathological characteristics, Tx modality for brain metastasis, and chemotherapy. Results: The median OS for all pts after the initiation of first-line chemotherapy was 9 months. In univariate analysis, pts who received TKI (13 months versus 6 months, p= 0.001) and third- or further-line chemotherapy (15 months versus 6 months, p< 0.001) had significantly longer median OS. The presence of extracranial extrathoracic metastasis, number of brain metastasis, and Tx modality for brain metastasis showed no significant association with OS. In multivariate analysis, third- or further-line chemotherapy (24 pts) was the only independent prognostic factor for favorable OS ( p< 0.001). Pts who underwent third- or further-line chemotherapy were characterized by high proportion of non-squamous histology ( p= 0.016), extracranial extrathoracic metastasis ( p= 0.015), and TKI Tx ( p< 0.001). Conclusions: The present study suggests that judicious but active use of chemotherapy after appropriate Tx for brain metastasis may result in favorable outcome in NSCLC pts with synchronous brain metastasis, regardless of the number of brain metastatic lesions or local Tx modalities.

Background: The ratio of involved to retrieved lymph nodes (LNR) is suggested as a prognostic factor in operable breast cancer. However, there are conflicting results regarding its clinical significance after neoadjuvant chemotherapy. We investigated the prognostic value of LNR with a thorough evaluation of potential prognostic factors in a large cohort constructed from Health Insurance Review and Assessment Service database of Korea. Patients and method: This retrospective analysis is based on the data of 814 patients with clinical stage II/III breast cancer treated with four cycles of adriamycin/cyclophosphamide (AC) followed by four cycles of docetaxel (DOC) before surgery. We evaluated the clinical significance of the LNR (3 categories: Low, 0-0.20 vs. Intermediate, 0.21-0.65 vs. High, 0.66 -1.00) using Kaplan-Meier method, log-rank test, and Cox proportional hazard regression model. Result: A total of 799 patients underwent breast surgery (Median age 45, range 16-74; Mastectomy 369, Lumpectomy 380, and Others 50). Axillary lymph node dissection was performed in 704 (88.1%) patients. Pathologic complete response (pCR, pT0/isN0) was achieved in 129 (16.1%) of 799 patients (HR+/HER2-, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; TNBC 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range 0-42) and 13.98 (range 1-64), respectively. The mean LNR was 0.17 (Low, 574 [71.8%]; Intermediate, 170 [21.3%]; High, 55 [6.9%]). In univariate analysis, LNR was significantly associated with worse relapse-free survival (3-yr RFS rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; P Multivariate analysis for relapse-free survival P-valueHR95%CIAGE ( Conclusion: LNR is not superior to ypN-stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. Citation Format: Se Hyun Kim, Jee Hyun Kim, Tae-Yong Kim, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, In Hae Park, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Kyung Hae Jung. Prognostic value of axillary nodal ratio after neoadjuvant chemotherapy of AC followed by docetaxel: A multicenter retrospective cohort study [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 P6-08-33.

Backgrounds A pegylated form of recombinant granulocyte-colony stimulating factor (G-CSF) was developed for prophylactic use in breast cancer. The aim of this study was to evaluate the efficacy and safety of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer. Methods A total of 61 patients receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were randomized in cycle 1 to receive daily injections of filgrastim (100 μg/m2) or a single subcutaneous injection of pegylated filgrastim DA-3031 at a dose of either 3.6 mg or 6 mg. Results The mean duration of grade 4 neutropenia in cycle 1 was comparable among the treatment groups (2.48, 2.20, and 2.05 days for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P = 0.275). No statistically significant differences were observed in the incidence of febrile neutropenia between the treatment groups (9.5 %, 15.0 %, and 5.0 % for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P = 0.681) in cycle 1. The incidences of adverse events attributable to G-CSF were similar among the treatment groups. Conclusions Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy.