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378 Background: BTC is a rare, heterogenous cancer with poor prognosis. Reports on immunogenic features of BTC suggest checkpoint inhibition may result in antitumor immune responses, and limited clinical activity has been seen with single agents in advanced settings. Durvalumab (PD-L1 inhibitor) + GemCis showed promising antitumor activity in advanced BTC in a phase 2 study. TOPAZ-1 (NCT03875235) is the first global phase 3 study to evaluate first-line immunotherapy + GemCis in advanced BTC. Methods: In this double-blind study, pts previously untreated for unresectable locally advanced, recurrent, or metastatic BTC were randomized 1:1 to receive durvalumab (1500 mg every 3 weeks [Q3W]) or placebo + GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles, followed by durvalumab (1500 mg Q4W) or placebo until disease progression or unacceptable toxicity. Randomization was stratified by disease status (initially unresectable, recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer). The primary objective was to assess overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff for this interim analysis (11 August 2021), 685 pts were randomized to durvalumab + GemCis (n=341) or placebo + GemCis (n=344; Table). The primary objective was met: durvalumab + GemCis significantly improved OS vs placebo + GemCis (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.66–0.97; p=0.021). PFS was also significantly improved with durvalumab vs placebo (HR, 0.75; 95% CI, 0.64–0.89; p=0.001). ORR was 26.7% with durvalumab and 18.7% with placebo. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 62.7% of pts receiving durvalumab and 64.9% of pts receiving placebo. TRAEs led to discontinuation of any study medication in 8.9% of pts receiving durvalumab and 11.4% of pts receiving placebo. Conclusions: In pts with advanced BTC, durvalumab + GemCis significantly improved OS and PFS vs placebo + GemCis with manageable safety, indicating durvalumab + GemCis may be a new first-line standard of care regimen. Clinical trial information: NCT03875235. [Table: see text]

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In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.

Little is known about the frequency of germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the distribution of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of women from Shanghai, China.Study subjects totaled 1306, and included 645 women with breast cancer, 342 women with benign breast disease, and 319 unaffected controls, born between 1924 and 1958, selected from women enrolled in a randomized trial of Breast Self-Examination in Shanghai, China. Women were selected without regard to family history of breast or ovarian cancer. All of the coding regions and exon-intron boundaries were screened. Data were analyzed with respect to age at diagnosis, and family history of breast and ovarian cancer.The prevalence of known disease-associated mutations in women with breast cancer was 1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease-associated mutations, respectively.Overall, these results suggest that inherited susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women with a family history of breast cancer is comparable between women from Shanghai and Caucasian women of Western European descent. Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent. IntroductionAlthough the incidence of breast cancer in China is about one-third that in the United States (1), the overall rate of breast cancer in women from China has been increasing (2). Little is known regarding the role of inherited susceptibility genes in breast cancer risk among Chinese women. To develop genetic screening guidelines for both Chinese women and United States women of Chinese descent, a population-based assessment of BRCA1 and BRCA2 germ-line mutation distribution and frequency is needed.To date, information regarding the frequency of BRCA1 and BRCA2 mutations in Chinese women with breast cancer has been derived from two small hospital-based reports. In the first, 76 consecutive breast cancer cases diagnosed before age 40, and 16 women with a family history of breast or ovarian cancer, were screened for germ-line mutations in BRCA1 (3). Protein truncating mutations were observed in 8.6% of women. In the second study, 3.8% of 130 tumors collected from mastectomy patients in Hong Kong were found to carry protein-truncating mutations in BRCA1 (4). The prevalence was 8.0% in patients diagnosed under age 45 (4). In the same study, investigators observed a single variant, 589delCT, in three unrelated patients from within a single province of Southern China, suggesting a possible founder effect. However a later more detailed study of 60 early onset breast cancer cases did not reveal any additional carriers (4, 5). Neither study examined the role of BRCA2 mutations in Chinese women.Studies of women...