Purpose YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.
Results In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.
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Choong-kun Lee, Minkyu Jung, Hyo Song Kim, Inkyung Jung, Dong Bok Shin, Seok Yun Kang, Dae Young Zang, Ki Hyang Kim, Moon Hee Lee, Bong-Seog Kim, Kyung Hee Lee, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Sun Young Rha
Cancer Res Treat. 2019;51(1):1-11. Published online February 5, 2018
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/m2 on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2 /day on days 1-14 plus cisplatin 60 mg/m2 on 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.
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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
Medicalrecords of 524 breast cancer patientswith 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 therapywas administered to 413 patientswith 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.
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Yeon Hee Park, Tae Yong Kim, Young-Hyuck Im, Keun-Seok Lee, In Hae Park, Joohyuk Sohn, Soo-Hyeon Lee, Seock-Ah Im, Jee Hyun Kim, Se Hyun Kim, Soo Jung Lee, Su-Jin Koh, Ki Hyeong Lee, Yoon Ji Choi, Eun Kyung Cho, Suee Lee, Seok Yun Kang, Jae Hong Seo, Sung-Bae Kim, Kyung Hae Jung
Cancer Res Treat. 2017;49(2):423-429. Published online August 3, 2016
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.
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Se Hyun Kim, Kyung Hae Jung, Tae-Yong Kim, Seock-Ah Im, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, Sarah Park, In Hae Park, Keun Seok Lee, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Jee Hyun Kim
Cancer Res Treat. 2016;48(4):1373-1381. Published online March 23, 2016
Purpose
The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy.
Materials and Methods
This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model.
Results
A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2– subtype.
Conclusion
LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2– patients is notable and worthy of further investigation.
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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.
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Purpose This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer.
Materials and Methods A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)- AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS).
Results In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle.
Conclusion Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.