Chikako Shimizu

In the original publication, Tables 4 and 5 have not been published in a readable format. The corrected clear version is given in this Correction.

Cancer is rare among adolescents and young adults (AYA). Affected persons need generation-specific attention and care; however, no nationwide study has investigated the medical care structure for AYA cancer treatment in Japan.

The clinical utility and prognostic impact of presumed primary breast or ovarian cancer among patients with an unfavorable subset of cancer of unknown primary site (CUP) remains unclear. We aimed to evaluate the clinical relevance of the presumed primary site of CUP and the clinical outcome of site-specific therapy based on such presumptions. Patients referred to our center who were diagnosed with unfavorable-subset CUP and treated between April 2007 and March 2015 were enrolled in this study. Data were collected retrospectively from the hospital database and electronic medical records. Presumptive primary breast or ovarian cancer was based on histological and immunohistochemical analyses and metastatic patterns. The outcomes of patients with unfavorable-subset CUP with a putative primary site in the breast or ovary (P-CUP) and of patients with unfavorable-subset CUP, but without P-CUP (U-CUP), were assessed. A total of 780 patients were referred to our hospital with malignancy of unknown origin. Of these, 409 patients were diagnosed with CUP and 344 patients with unfavorable-subset CUP. Following clinicopathological examination, 40 (11.6%) of the 344 patients had P-CUP and the remaining 303 (88.3%) patients had U-CUP. In total, 136 patients received chemotherapy (22 with P-CUP and 114 with U-CUP). Among the 22 patients with P-CUP, three received hormonal therapy for breast cancer, and 19 received chemotherapy based on the presumed primary organ (breast, 4; ovaries, 15). Conventional platinum-based chemotherapy was administered to 105 patients with U-CUP and non-platinum drug treatment to nine patients. The objective response rates were 61.1% (95% confidence interval [CI]: 38.6–83.6) and 41.1% (95% CI: 31.8–50.4) for patients with P-CUP and U-CUP, respectively. The median overall survival durations were 50.0 months and 16.9 months (log-rank: P = 0.002) for patients with P-CUP and U-CUP, respectively. P-CUP was identified as an independent predictor of good prognosis according to multivariate analysis. Patients with P-CUP had higher response rates and a better prognosis compared with patients with U-CUP. It might thus be reasonable to classify this subset as a new category of CUP with a favorable prognosis.

The efficacy and safety of eribulin in patients with locally advanced or metastatic breast cancer has been demonstrated in phase III trials. However, as patients receiving eribulin in daily practice do not necessarily meet all the eligibility criteria of clinical trials, data for such patients are limited. We identified patients with locally advanced or metastatic breast cancer, treated with eribulin monotherapy between July 2011 and December 2015 at the National Cancer Center Hospital, Tokyo, Japan. Patients who would have met the following eligibility criteria from the EMBRACE trial were included in the eligible group, and the rest were included in the ineligible group: 1) Eastern Cooperative Oncology Group Performance status 0–2; 2) adequate function of principal organs; and 3) absence of active infection. We compared the relative dose intensity (RDI), tumor response, progression-free survival (PFS), overall survival (OS), and adverse events between the groups. Nominal and continuous values were compared using the Fisher’s exact test and Mann-Whitney U test, respectively. Survival outcomes were determined using Kaplan-Meier estimation, and between-group differences were assessed using the log-rank test. Of the 203 patients included, 34 were classified into the ineligible group and 169 into the eligible group. Initial dose reduction and treatment discontinuation due to adverse events (AEs) were more common in the ineligible group (initial dose reduction: 23.5% in the ineligible group vs. 7.7% in the eligible group, p = 0.011; treatment discontinuation due to AEs: 11.8% vs. 3.0%, p = 0.045). However, RDI (66% vs. 71%, p = 0.130), response rate (15.6% vs. 18.1%, p = 1.000), PFS (3.7 months vs. 4.0 months, p = 0.913), OS (11.5 months vs. 16.1 months, p = 0.743), AEs requiring hospitalization (5.9% vs. 6.5%, p = 1.000), and grade 3/4 AEs were similar in both groups. PFS, OS, AEs requiring hospitalization, and discontinuation due to AEs in the eligible group were comparable to those found in previous phase III trials. The safety and efficacy of eribulin monotherapy was demonstrated in a broader patient population than that eligible for clinical trials. Eribulin may be a treatment option in these patients with locally advanced or metastatic breast cancer, considering dose reduction and pre-existing dysfunctions.

E21511 Background: End-of-life discussion (EOLd) including information about incurability, prognosis, the site of death, and do-not-resuscitate (DNR) status is considered indispensable for advanced care planning (ACP). However, the preference for EOLd in cancer patients has not been elucidated. Objective: To clarify the preferences of EOLd in Japanese patients with newly diagnosed advanced or recurrent cancer. Methods: A multi-center questionnaire survey was conducted on Japanese adult patients with breast cancer, pancreatic cancer, or sarcoma, who were diagnosed as incurable within the past three months. We asked patients whether they would like to have EOLd with their physician at the time of survey. Factors related to preferences of EOLd were analyzed using chi-square or Mann-Whitney U-test. Results: For 1 year from August 2015, we distributed the questionnaire to 251 patients at five centers. Responses were obtained from 159 patients (45 males, 113 females) (response rate: 63%). The median age was 65 years (range: 29-86). 93 patients (59%) answered they would like to have EOLd, while 60 patients (38%) answered they would not. In univariate analyses, elderly patients (odds ratio [OR]: 1.03; p = 0.027), patients having worse performance status (OR: 1.988; p = 0.03), and with any physical symptoms (OR: 1.533; p = 0.044) preferred to have EOLd. On the other hand, patients who perceived “being able to sufficiently fight the disease” ( p = 0.021) and “living without being aware of the disease” ( p = 0.004) as important were reluctant to have EOLd. 114 patients (72%) answered they wanted to know their life-time prognosis. Employed patients preferred to know their prognosis (OR: 8.919; p = 0.004) while patients who had received chemotherapy did not (OR: 0.313; p = 0.009). Conclusions: Even just after the diagnosis as an incurable disease, more than half of patients with advanced cancer were willing to have EOLd with their treating physician. Patients’ preference of knowing about life-time prognosis was affected by their social and medical experience.

Paclitaxel (PTX) is a key drug used in the treatment of ovarian cancer. One well-known adverse effect is chemotherapy-induced peripheral neuropathy (CIPN), which can often lead to the discontinuation of chemotherapy or decreased quality of life. There are some pivotal clinical trial data for patients with ovarian cancer, which have shown the incidence of CIPN according to severity but have not shown detailed data. Therefore, we retrospectively investigated the incidence, timing, and severity of CIPN associated with PTX-containing regimens in 142 patients with ovarian cancer. Patients received dose-dense paclitaxel/carboplatin (TC) (n = 93, 65.5％), TC (n = 36, 5.4％), or weekly TC (n = 13, 9.1％). CIPN occurred in 130 patients (91.5％); 67 of 130 patients (51.5％) had CIPN of Grade 2 or higher. The median cumulative dose associated with the onset of CIPN was 320 mg/m². The median cumulative dose associated with the onset of CIPN was 400 mg/m² for Grade 1, 320 mg/m² for Grade 2, and 175 mg/m² for Grade 3. Patients with CIPN onset at lower doses of PTX developed more severe CIPN (P < 0.05). Further investigation of optimal timing to prevent and therapeutic strategy to treat CIPN is required.

Purpose Whether age and inter-individual variability of pharmacogenetics are risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive. This study was conducted to evaluate the influence of previously investigated single nucleotide polymorphisms (SNPs) and age, using genotype data from a prospective study of paclitaxel-related toxicity in Japanese patients with breast cancer. Methods Peripheral blood mononuclear cells from 127 Japanese women with breast cancer who received weekly adjuvant paclitaxel were used to genotypes SLCO1B3 T334G (rs4149117), CYP2C8 A1196G (rs10509681), ABCB1 C1236T (rs1128503), ABCB1 G2677T/A (rs2032582), and ABCB1 C3435T (rs1045642). Genotypic and clinical factors were investigated for associations with PIPN. Results Of the five SNPs evaluated, no SNPs were significantly associated with grade 2 or higher PIPN. However, ABCB1 1236 TT showed a trend to associate with grade 2 or higher PIPN compared to ABCB1 CT/CC (odds ratio 2.1, 95% CI 0.991–4.548, p = 0.051). In subgroup analysis, patients ≥60 years old with an ABCB1 1236 TT had a higher incidence of ≥grade 2 PIPN compared to patients with CT or CC genotype (p = 0.027). On multivariable analysis, age ≥60 years and the ABCB1 1236 TT showed a significant association with ≥grade 2 PIPN (p = 0.005 and p = 0.034, respectively). Conclusions ABCB1 1236 TT genotype and older age might be a predictor of PIPN, which diminishes quality of life of cancer survivors.

211 Background: Smartphone-applications have been used for self-care, but not all applications have a sufficient level of efficacy. We evaluated the feasibility of a new smartphone application (the App) which has two main functions—diary function and SNS function—and investigated the characteristics of active users. Methods: Patients who visited the Breast and Medical Oncology or GI Medical Oncology divisions at National Cancer Center Hospital were recruited between March and April in 2016. Participants could use the App for 28 days. Web-based survey was performed before and 28 days after using the App. The primary endpoint was Daily Active User (DAU) rate (the number of daily log-in user divided by the number of patients who completed installation). A mean DAU rate higher than 20% was predetermined as feasible. The secondary endpoints were daily diary function user rate, daily SNS function user rate, and overall user rate and change of Edmonton Symptom Assessment System Revised Japanese version (ESAS-r-j) before and after the App use. “Active user” was defined as a participant who used the AppeWe more than median active days for diary or SNS function. Duration of App use was counted from the date of installation to the date of last use, and overall user rate was calculated by Kaplan Meier method. Results: One-hundred and four patients (96%) completed the App installation and answered the first survey. All patients were followed for 28 days. The mean DAU rate was 50.9%. Active diary function user rate was 53% and active SNS function user rate was 40%. Overall user rate was 87.5%. Diary function was used more frequently by male patients than female, and non-breast cancer patients. SNS function was used more frequently by unemployed patients than others, and by patients younger than 40 y/o. We could evaluate the change of ESAS-r-j score in 80 patients who answered the second survey. There was a significant improvement of depression score among patients who were single and who had metastatic disease. Conclusions: The App was considered feasible. Gender, cancer type, job status, and age may influence the behavior of the App use. The App may improve patients’ psychological symptoms, but further investigations are warranted to reveal the clinical utility of the App.

1080 Background: Metastatic TNBC has a poorer prognosis compared with other subtypes because of the lack of a confirmed effective target. Eribulin is a standard treatment for metastatic TNBC and olaparib (Lynparza), a PARP inhibitor, has shown efficacy in breast cancer with germline (g)BRCA1/2 mutations. We designed this Phase I/II trial with an expectation of a synergistic effect for metastatic TNBC patients (pts) enrolled, irrespective of gBRCA1/2 mutation status. In Phase I, we reported at ASCO 2015 the recommended dose of olaparib tablets was 300 mg BID. We will present the efficacy and safety of this combination treatment from phase II. Methods: Pts with advanced or metastatic TNBC previously treated with anthracyclines and taxanes were eligible. Confirmation of a BRCA1/2 mutation was not mandatory before enrollment. This trial was conducted at 8 institutions in Japan. According to the results from Phase I, 1.4 mg/m2 of eribulin was administered intravenously on Days 1 and 8. Olaparib tablets were orally administered at a dose of 300 mg BID. The primary efficacy endpoint was tumor response rate. Results: From June 2014 to December 2014, 24 pts were enrolled. The median age was 46 years old (range: 27 to 73). The median number of prior chemotherapy regimens was 3 (range: 2 to 6). Sixteen pts (66.7%) had visceral metastasis and 8 non visceral metastasis. The relative dose intensity of eribulin was 74.9% and olaparib 75.4%. The response rate was 37.5% (95% CI: 18.8–59.4), including CR in 1 pt. Median progression free survival was 4.2 months (95% CI: 2.7–7.6). The median overall survival was not reached and 11 pts died. Severe adverse events (G3 and G4) were leukocytopenia (83.3%), neutropenia (83.3%), febrile neutropenia (33.3%), anemia (37.5%) and thrombosis (8.3%). Conclusions: The combination of olaparib and eribulin indicates a promising clinical interaction in pts with metastatic TNBC, without intolerable adverse events. The next step is exploratory research into the relationship between gBRCA1/2 mutation status and/or HRD, and the clinical efficacy of this combination treatment. Clinical trial information: 12.