The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
WCIM 2014 SEOUL KOREA 399
Slide Session
OP2-4 Breast Cancer
Incidence and Time Course of Everolimus-Related Adverse Events in Postmenopausal Hormone Receptor- Positive Advanced Breast Cancer; Single Center Experience in Korea
Shinkyo Yoon1, Jeong Eun Kim1, Jin-Hee Ahn1, Kyung Hae Jung1, Sung-Bae Kim1 Asan Medical Center Department of Oncology, Korea1
Background: Everolimus (EVE) combined with an exemestane (EXE) have shown im- proved progression-free survival (PFS) in patients with hormone receptor-positive (HR+) advanced breast cancer (ABC) following treatment with nonsteroidal aromatase inhibi- tors. The aim of this study is to investigate the incidence and time course of EVE-related adverse events (AEs) in treatment with EVE+EXE for postmenopausal HR+ABC patients.
Methods: A total 56 patients were retrospectively reviewed between Jan 2013 - Jun 2014. Primary end point was to demonstrate incidence and time course of EVE-related AEs. Secondary end points was to analysis for objective response rate (ORR) and fac- tors associated with PFS.
Results: The median follow-up duration was 3.4 months (0.47-15.0). The median age was 56 years (35-78), 73% of patients showed sensitivity to previous endocrine therapy. The most frequently reported all-grade AEs included class-effect related hy- perglycemia (73.2%), hypercholesterolemia (69.6%), and stomatitis (57.1%). None of patients experienced non-infectious pneumonitis. The cumulative risks of stomatitis, rash, fatigue, and anorexia at 2 weeks and 6 weeks are shown at fi gure 1. Overall, there were 25.0% of dose reduction and 17.9% of dose interruption. The most com- mon cause of dose reduction or interruption was stomatitis. The median PFS was 10.2 months and ORR was 23.2%. Factors associated with PFS were duration of most recent hormonal, positive status for progesterone receptor and lines of chemotherapy between EVE and EVE+EXE (fi gure 2). AEs such as stomatitis, rash, fatigue, and ano- rexia showed no association with PFS.
Conclusions: Hyperglycemia, stomatitis, and fatigue were the most common AEs and stomatitis was the most common cause of dose reduction or interruption. Understand- ing the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.
OP2-10 Others
Clinical Outcomes of Perioperative High-Dose Methotrexate in Patients at Age 15 Years and Older with Non-Metastatic, High-Grade Osteosarcoma
Eunyoung Lee1, Tae Min Kim1, Han-Soo Kim2, Bhumsuk Keam1, Ilkyu Han2, Se-Hoon Lee1, Dong-Wan Kim1, Il Han Kim3, Dae Seog Heo1
Department of Internal Medicine, Seoul National University Hospital, Korea1, Department of Orthopedic Surgery, Seoul National University Hospital, Korea2, Department of Radiation Oncology, Seoul National University Hospital, Korea3
Background: Multi-agent perioperative chemotherapy is the standard treatment for non-metastatic, high-grade osteosarcoma. Due to the rarity of well-designed con- trolled trials, the addition of high-dose methotrexate (HDMTX) is controversial. There- fore, we evaluated the effi cacy of perioperative HDMTX in non-metastatic, high-grade osteosarcoma in a single center.
Methods: Sixty-four patients at age 15 years and older were diagnosed as non-meta- static, high-grade osteosarcoma in Seoul National University Hospital between January 2000 and November 2013. Clinical factors, tumor necrosis grade, and treatment out- comes were analyzed. Preoperative chemotherapy included HDMTX plus doxorubicin and cisplatin (N = 49); HDMTX plus ifosfamide and cisplatin (N = 4); doxorubicin and cisplatin (N = 9); and other (N = 2). Postoperative regimens were based on the tumor necrosis rate (%): = 90% necrosis, same regimens; and < 90% necrosis, different regi- mens as compared with preoperative ones.
Results: Fifty-three (83%) received preoperative HDMTX-based regimens. After cu- rative resection, thirty-eight (59%) including 7 patients without preoperative HDMTX exposure received postoperative HDMTX-based regimens. Twenty-six (41%) includ- ing 22 patients with exposure to preoperative HDMTX received postoperative non- HDMTX-based regimens. Patients who received preoperative HDMTX-based regimens showed the better response defi ned as necrosis = 90% than those treated with non- HDMTX-based regimens (35% vs. 0%, HR=1.333, 95% CI 1.124-1.581; P=0.02). How- ever, survival outcomes were similar between preoperative HDMTX and non-HDMTX groups (median progression-free survival, 10.7 vs. 11.0 months, P=0.573; and 5-year survival rate, 61.3 vs. 58.3%, P=0.586).
Conclusions: The addition of HDMTX in preoperative regimens induced significant tumor necrosis in non-metastatic, high-grade osteosarcoma. Survival outcomes were similar regardless of preoperative use of HDMTX.
OP3-1 Gastric Cancer
Prognostic Implications of Immunosuppressive Protein Expression in Tumors as Well as Immune Cell Infi ltration within the Tumor Microenvironment in Gastric Cancer
Jin Won Kim1, Kyung Han Nam3, Sang-Hoon Ahn4, Do Joong Park4, Hyung-Ho Kim4, Se-Hyun Kim1, Hyun Chang5, Jeong-Ok Lee1, Yu Jung Kim1, Hye Seung Lee2, Jee Hyun Kim1, Soo-Mee Bang1, Jong Seok Lee1, Keun-Wook Lee1
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National Univer- sity Bundang Hospital, Seoul National University College of Medicine, Korea1, Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Korea2, De- partment of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Korea3, Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Korea4, Department of Hematology and Medical Oncology, International St. Mary’s Hospital, Korea5 Background: There are few data on the clinical implications of the immunosuppressive protein expression in tumors and immune cell infi ltration within the tumor microenvi- ronment in patients with gastric cancer (GC).
Methods: In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(+) or PD-1(+) cells] within the tumor microenvironment were measured by using immunohistochemical analysis.
Results: Positive P D-L1, CTLA-4, and IDO expressions were observed in 43.6%,65.8%, and 47.7%, respectively. The expressions of PD-L1, CTLA-4, or IDO were related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (P < 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(+) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6% vs. 66.9%;
5-year OS rate, 83.0% vs. 69.1% (P-values < 0.05)]. Survival outcomes were also better in patients with higher density of CD3(+) cells within the tumor microenvironment than those with lower density of CD3(+) cells [5-year DFS rate, 80.9% vs. 67.0%; 5-year OS rate, 82.5% vs. 68.0% (P-values < 0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables.
Conclusions: GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and CD3- high tumor microenvironment are favorable prognostic markers in GC.
