Association of tumors having Epstein–Barr virus in surrounding lymphocytes with poor prognosis

Abstract Infection with certain viruses is an important cause of cancer. The Pan‐Cancer Analysis of Whole Genomes (PCAWG) Consortium recently analyzed the whole‐genome sequencing (WGS) data from 2656 cases across 21 cancer types, and indicated that Epstein–Barr virus (EBV) is detected in many different cancer cases at a higher frequency than previously reported. However, whether EBV‐positive cancer cases detected by WGS‐based screening correspond to those detected by conventional histopathological techniques is still unclear. In this study, to elucidate the involvement of EBV in various cancers, we reanalyzed the WGS data of the PCAWG cohort combined with the analysis of clinical samples of gastric and pancreatic cancer in our cohort. Based on EBV copy number in each case, we classified tumors into three subgroups: EBV‐High, EBV‐Low, and EBV‐Negative. The EBV‐High subgroup was found to be EBV‐positive in the cancer cells themselves, whereas the EBV‐Low subgroup was EBV‐positive in the surrounding lymphocytes. Further, the EBV‐Low subgroup showed a significantly worse prognosis for both gastric cancer and across cancer types. In summary, we classified tumors based on EBV copy number and found a unique cancer subgroup, EBV‐positive in the surrounding lymphocytes, which was associated with a poor prognosis

Efficacy and safety of pegfilgrastim biosimilar MD‐110 in patients with breast cancer receiving chemotherapy: Single‐arm phase III

Abstract Introduction Pegfilgrastim is indicated to decrease the incidence of chemotherapy‐induced febrile neutropenia. It is the first granulocyte‐colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G‐LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD‐110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open‐label, single‐arm study investigated the efficacy and safety of MD‐110 in early‐stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy. Methods A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 (TC) for four cycles on day 1 of each cycle. MD‐110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm3). The safety endpoints were adverse events and the presence of antidrug antibodies. Results The mean (SD) duration of severe neutropenia for MD‐110 was 0.2 (0.4) days. The upper limit of the two‐sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients. Conclusion MD‐110 was effective against chemotherapy‐induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI‐205230)

Fulvestrant with or without anti‐HER2 therapy in patients in a postmenopausal hormonal state and with ER‐positive HER2‐positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG‐C06)

Abstract Background The role of endocrine therapy in the treatment of patients in a postmenopausal hormonal state and with estrogen receptor (ER)‐positive, human epidermal growth factor receptor 2 (HER2)‐positive advanced or metastatic breast cancer (AMBC) is unclear. Methods We analyzed the data from 94 patients with ER‐positive HER2‐positive AMBC enrolled in the Safari study (UMIN000015168), a retrospective cohort study of 1072 ER‐positive AMBC patients in a postmenopausal hormonal state who received fulvestrant 500 mg (F500): (1) to compare time to treatment failure (TTF) and overall survival (OS) by treatment group, and TTF by treatment line; (2) in patients who received endocrine therapy (including F500) or anti‐HER2 therapy as initial systemic therapy before chemotherapy, to investigate relations between TTF for the first‐line therapy or time to chemotherapy (TTC) and OS; (3) to investigate factors associated with OS. Results The TTF was longer in the patients treated with F500 as first‐ or second‐line therapy (n = 20) than in those who received later‐line F500 therapy (n = 74) (6.6 vs. 3.7 months; HR, 1.98; p = 0.014). In the 59 patients who received endocrine therapy or anti‐HER2 therapy as initial systemic therapy before chemotherapy, those with TTC ≥3 years had longer median OS than those with TTC <3 years (10.5 vs. 5.9 years; HR, 0.32; p = 0.001). Longer TTC was associated with prolonged OS. Conclusions In patients with ER‐positive HER2‐positive AMBC enrolled in the Safari study, TTF was longer in patients who received F500 as first‐ or second‐line therapy. In patients who received chemotherapy‐free initial systemic therapy, the prolonged OS in those with TTC ≥3 years suggests that this value may be a helpful cut‐off for indicating clinical outcomes