bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line of camrelizumab plus pyrotinib and chemotherapy in HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma: A dose escalation and expansion phase I study.
Authors: Zhu Liangjun , Li Sheng , Bao Jun , Li Xiaoyou , Yang Quanliang , Xu Junying , Chen Surong , Feng Ge , Gao Chao , Feng Lin , Lu Bin , Miao Min , Ni Xinchu , Wang Guofang , Yang Lei 
Published: January 2023

356 Background: The combination of PD-1 and HER2 blockades showed potential benefit for patients with HER2-positive gastric cancer. This study aimed to investigate the safety and efficacy of camrelizumab plus pyrotinib and chemotherapy in the first-line setting for HER2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Methods: This phase I, open-label, clinical trial (ChiCTR2000029717) included dose-escalation and dose-expansion cohorts. Patients aged 18 or older with HER2-positive G/GEJ cancer were enrolled. In dose-escalation phase, patients were administrated with three-week cycle of oral pyrotinib 240mg, 320mg or 400mg daily, intravenous camrelizumab 200mg and oxaliplatin 130mg/m2 on day 1, and oral capecitabine 1000mg/m2 twice a day for two weeks followed by one week off until unacceptable toxicities, progressive disease or death. Additional patients were enrolled in a dose-expansion phase and received maximum tolerated dose determined in the dose-escalation cohort. The primary endpoints were the safety and objective response rate (Response Evaluation Criteria in Solid Tumors version 1.1). Results: Between June, 2020 and June, 2022, a total of 31 patients were enrolled, with 9 patients in the dose-escalation phase (three patients received pyrotinib 240mg, 320mg or 400mg each) and 22 in the dose-expansion phase. During dose-escalation, five patients experienced six dose-limiting toxicity, including diarrhea (n=4), vomiting (n=1) and decreased appetite (n=1). The maximum tolerated dose of pyrotinib was 320 mg, which was chosen for dose-expansion. For 25 patients received pyrotinib 320 mg, 13 (52.0%) developed grade 3 or higher adverse events (AEs), and 6 (24.0%) discontinued treatment due to AE. The most common AE of any grade was diarrhea (96.0%), followed by vomiting (60.0%), decreased appetite (56.0%) and anemia (56.0%). The objective response rate and disease control rate were 96.0% and 100%, respectively. The 12-month progression-free survival rate and overall survival rate were 77.1% and 89.3%, respectively. Conclusions: Camrelizumab plus pyrotinib and chemotherapy showed promising efficacy in the first-line treatment of HER2-positive G/GEJ cancer, with acceptable safety profiles. The study is ongoing. Clinical trial information: ChiCTR2000029717 .[Table: see text]
Camrelizumab plus apatinib for immunochemotherapy-treated advanced esophageal squamous cell carcinoma: Preliminary results of cohort 2 in CAP 02 study.
Authors: Wang Feng , Wang Junsheng , Meng Xiangrui , Luo Zhiquan , Xia Jin , Hong Yong-Gui , Lu Ping , Ji Yinghua , Shan Zheng-Zheng , Fan Qingxia 
Published: January 2023

384 Background: CAP 02 study (NCT03736863) is a single-arm phase 2 study to evaluate the efficacy and safety of camrelizumab plus apatinib (a VEGFR2 inhibitor) as second-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). Cohort 1 has been published recently, which enrolled patients who progressed after or were intolerant to first-line chemotherapy. The results showed an encouraging median overall survival (OS) of 15.8 months. Here, we reported the preliminary results of cohort 2. Methods: Cohort 2 enrolled unresectable locally advanced, locally recurrent, or metastatic ESCC patients aged 18-75 years with ECOG performance status of 0-1 who had progression on or were intolerant to first-line immunochemotherapy. The disease should be controlled without progression for at least three months during the first-line treatment. Patients received camrelizumab (200 mg Q2W) and apatinib (250 mg QD) until disease progression, intolerable toxicity, or withdrawal for other reasons. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate, progression-free survival (PFS), duration of response, time to response, OS, 3/6-month PFS rates, 6/9/12-month OS rates, and safety. Results: At the data cutoff (Sep 21, 2022), 33 of the planned 40 patients with an average of 68 years old had been enrolled, including 24 (73%) males and 24 (73%) patients with an ECOG PS score of 1. Twenty-one patients (64%) were previously treated with camrelizumab combined chemotherapy and 12 with other immunochemotherapy. Among the 17 evaluable patients, seven had the best overall response of partial response and nine with stable disease; the ORR was 41%. A total of 22 patients (67%) had treatment-related adverse events (TRAEs), with 12 patients (36%) with grade≥3. The most common TRAEs included white blood cell count decreased (11 patients, 33%), hypokalaemia (9, 27%), and alanine aminotransferase increased (8, 24%). Conclusions: Current results suggested the preliminary efficacy of second-line camrelizumab plus apatinib in patients with immunochemotherapy-treated advanced ESCC, with an acceptable safety profile. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03736863 .
Real-world survival of patients (pts) with colorectal adenocarcinoma liver metastases (CRLM) treated with transarterial radioembolization (TARE).
Authors: Mahmood Sharmeen , Hagopian Garo Greg , Sadeghi Ben , Kuo Jeffrey V , Imagawa David , Fernando Dayantha , Abi-Jaoudeh Nadine , Dayyani Farshid 
Published: January 2023

40 Background: While TARE with yttrium-90 (Y90) microspheres can induce tumor responses and improve progression-free survival (PFS) in pts with CRLM, randomized trials have not shown an overall survival (OS) benefit. It is unclear whether this is due to suboptimal pt selection and/or trial design vs. possibly a radiation-induced delayed liver damage which compromises OS. The objective was to describe real world OS with TARE for pts evaluated at an academic center (University of California Irvine) with a dedicated multidisciplinary liver tumor board (MTB). Methods: Retrospective study of consecutive pts with CRLM undergoing TARE between 01/2016-07/2020. We performed descriptive analyses for relevant pt and tumor characteristics, Wilcoxon Signed-Rank Test for comparison of continuous variables, and Kaplan-Meier estimates for survival. Results: N=55 pts were included. Follow-up time was at least 24 mo. Median age was 60 yrs (range 36-84), 61.8% were female, Caucasian/Hispanic/Asian/Other= 54.4%/16.4%16.4%/12.7%, ECOG 0/1/2= 32.7%/58.2%/9.1%, tumor sidedness: left/right/unknown 72.7%/23.6%/3.6%, number or prior lines of systemic treatment 1/2/3+= 38.2%/26.4%/21.8%. MSI-High= 3.6% and RAS/RAF mutations were present/absent/unknown in 34.5%/49.1%/16.4%. Baseline and post-TARE liver function tests are shown in the table. Median time from diagnosis to first TARE was 16.4 mo (1.7-95.6) and 36.4% were treated within the first 12 mo of diagnosis. Median OS from diagnosis and first TARE were 43.2 mo (29.5-68.7) and 16.7 mo (9.9-35.2), respectively. Conclusions: The observed OS of pts with CRLM treated with TARE with a mature follow-up of at least 2 years exceeds 40 mo, despite early integration of TARE in a third of the pts within the first 12 mo of diagnosis. Evaluation of pts with CRLM for TARE at experienced centers with dedicated MTB might lead to improved outcomes. [Table: see text]
A phase 2 study of durvalumab plus DOS (docetaxel, oxaliplatin, S-1) neoadjuvant chemotherapy followed by surgery and adjuvant durvalumab plus S-1 chemotherapy in patients with resectable locally advanced gastric cancer: An interim efficacy report.
Authors: Kim Hyung-Don , Ryu Min-Hee , Park Young Soo , Lee Jong Seok , Kang Yoon-Koo 
Published: January 2023

408 Background: The phase 3 PRODIGY study showed that neoadjuvant docetaxel, oxaliplatin and S-1 (DOS) chemotherapy, as part of perioperative chemotherapy, was effective and tolerable in Asian patients with resectable locally advanced gastric cancer (LAGC). The current study aimed to evaluate the efficacy and safety of neoadjuvant durvalumab plus DOS, which was followed by surgery and adjuvant durvalumab plus S-1 chemotherapy in patients with resectable LAGC. Methods: In this single-center, open-label, phase II study, patients with locally advanced gastric or gastroesophageal junction cancer (i.e., cT2/3N+ or cT4Nany) were enrolled. In patients with proficient mismatch repair protein (pMMR) tumors (main arm), 3 cycles of neoadjuvant durvalumab plus DOS were administered every 3 weeks, which was followed by surgery and adjuvant S-1 plus durvalumab administered every 6 weeks for 12 months. The primary endpoints were the rate of pathologic complete regression (pCR) and the safety. For an exploratory purpose, patients with deficient mismatch repair protein tumors (exploratory arm) were treated with 3 cycles of neoadjuvant durvalumab and tremelimumab every 4 weeks followed by surgery and adjuvant durvalumab administered every 4 weeks for 12 months. At this interim analysis, we report the results of patients with pMMR. Results: As of SEP 2022, 40 subjects with pMMR were enrolled and received ≥ 1 dose of neoadjuvant treatment. Thirty-five subjects completed 3 cycles of neoadjuvant treatment, and 31 received surgery as of the data cut-off. Among 31 patients who received surgery, a pCR was confirmed in 9 (29.0%), meeting the primary efficacy endpoint (8 pCR out of 40) early. Among those who received 3 cycles of neoadjuvant treatment, 3 (8.6%) experienced the predefined unacceptable severe toxicities during the neoadjuvant treatment: febrile neutropenia (n=2) and G4 neutropenia persisted for ≥ 7 days (n=1). Conclusions: The current study met its primary efficacy endpoint and is expected to meet the primary safety endpoint (<20%). Neoadjuvant durvalumab plus DOS followed by surgery and adjuvant durvalumab plus S-1 chemotherapy deserves to be investigated in a phase 3 trial in Asian patients with LAGC. Clinical trial information: 04221555 .
Investigation of predictive biomarkers in patients treated with atezolizumab monotherapy following definitive chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma (EPOC1802).
Authors: Bando Hideaki , Kumagai Shogo , Kotani Daisuke , Mishima Saori , Habu Takumi , Tsushima Takahiro , Hara Hiroki , Kadowaki Shigenori , Kato Ken , Chin Keisho , Yamaguchi Kensei , Kageyama Shun-ichiro , Hojo Hidehiro , Nakamura Masaki , Hidenobu Tachibana , Wakabayashi Masashi , Fukui Makoto , Fuse Nozomu , Nishikawa Hiroyoshi , Kojima Takashi 
Published: January 2023

416 Background: Platinum-based definitive chemoradiotherapy (dCRT) is the standard treatment for patients (pts) with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), invading the aorta, vertebral body, or trachea. However, complete response (CR) rates are low (11–25%), with a median overall survival (OS) of 9–10 months. We previously reported atezolizumab following dCRT indicated promising 42.1% of confirmed CR (cCR) rate and 65.8% of 12-months OS (Bando H, et al., ESMO Congress 2022 ). Methods: We investigated predictive biomarkers for cCR in this multicenter phase II study. PD-L1 tumor proportion score (TPS) was examined with VENTANA PD-L1. Immunological phenotypes of tumor microenvironments were assessed with multiplex immunohistochemistry (mIHC) and multi-color flow cytometry (FCM). Cancer gene aberrations and gene expression were investigated with whole exome and whole transcriptome sequencing (WES/WTS), respectively. Results: In 35 pts with an evaluable PD-L1 TPS, the cCR rates of <1% and ≥1% were 44.4% and 41.2%, respectively. In mIHC analysis of 28 pts, the number of CD3+CD8+PD-1+ T cells and CD3+CD8-FOXP3+ T cells prior to CRT in tumor tissue were significantly correlated with cCR and non-cCR, respectively (both are P<0.05). In FCM analysis of 19 pts, tumor-infiltrating PD-1+CD8+ T cells prior to CRT, after CRT, and after atezolizumab were significantly correlated with cCR (P<0.05). On the other hand, CTLA-4+FOXP3highCD45RA-CD4+ regulatory T cells (Treg cells) after CRT were significantly correlated with non-cCR (P<0.05). In WES of 27 pts, MYC amplification, EGFR mutation, PIK3CA mutation, PTEN mutation, and KEAP1 mutation were detected in pts with non-cCR. In WTS of 27 pts, gene expression signatures of IFN-γ response and inflammatory response were enhanced after CRT. Gene expression signatures of epithelial mesenchymal transition (EMT) and TGF-β signalings prior to CRT were significantly enriched in pts with cCR. Conclusions: Our biomarker analysis suggests that tumor-infiltrating PD-1+CD8+ T cells prior to CRT may be a predictive biomarker for cCR of CRT followed by atezolizumab, and that several driver gene abnormalities, cancer intrinsic signatures and tumor-infiltrating Treg cells are associated with treatment resistance. These findings could enable subsequent biomarker-selected clinical trials and lead to the development of novel cancer immunotherapeutic strategies. Clinical trial information: UMIN000034373 .
CA125 kinetics as a potential biomarker for ascites progression during taxane plus ramucirumab therapy in patients with advanced gastric cancer.
Authors: Ueda Akira , Yuki Satoshi , Ando Takayuki , Motoo Iori , Ito Ken , Kito Yosuke , Sakumura Miho , Ueda Yuko , Kajiura Shinya , Nakada Naokatsu , Nakajima Koji , Hosokawa Ayumu , Harada Kazuaki , Kawamoto Yasuyuki , Komatsu Yoshito , Yasuda Ichiro 
Published: January 2023

437 Background: Ascites and peritoneal metastases are major interruptive factors in sequential chemotherapy for advanced gastric cancer (AGC), although there are no established markers that predict ascites burden during treatment. Therefore, we aimed to clarify the association between serum CA125 and therapeutic efficacy for AGC treated with taxane plus ramucirumab (TAX/RAM). Methods: This multicenter retrospective study comprised AGC patients who received TAX/RAM in second or third line setting between Jun. 2015 to May 2019. Patient background and treatment outcome was assessed in CA125 elevated and non-elevated group before TAX/RAM (cut-off, 37 U/ml). The CA125 kinetics after chemotherapy was calculated based on baseline and first measure of CA125. Further, the association between early CA125 change and ascites burden during chemotherapy were evaluated based on optimal cut off value calculated receiver operating characteristic (ROC) curve analysis. Results: A total 73 patients from 5 hospitals were assessable. The proportion of poor PS, moderate/severe peritoneal effusion, low albumin was significantly larger in CA125 elevated group (n=31) than those in non-elevated group. The median value of CA125 before TAX/RAM was elevated according to ascites burden (none, 37.5 U/ml; mild, 57.9 U/ml; moderate/severe, 134.8 U/ml; p<0.001). The overall survival was significantly shorter in elevated group than that in non-elevated group (median, 8.2 vs. 14.6 months, p=0.0004). Baseline CA125 elevation and peritoneal metastasis were independent prognostic factors in multivariate analysis. After TAX/RAM, first-time measure of CA125 was performed in a median of day 28. The median change of CA125 was correlated with ascites response (CR/PR, -1.86%/day; SD, 0.28%/day; PD, 2.33 %/day, p<0.001). ROC curve analysis showed that the optimal cut-off value of CA125 kinetics for ascites progression was 0.0067%/day (specificity 74%, sensitivity 100%). The progression free survival in increased group was significantly shorter than that of non-increased group in patients with peritoneal dissemination (median, 2.5 vs 6.1 months, p=0.0008). Conclusions: The serum CA125 before TAX/RAM was associated with ascites burden. Further, early change of CA125 after TAX/RAM was associated with prognosis in AGC patients with peritoneal dissemination. CA125 monitoring may be biomarker in determining timing of treatment change.
Impact of high-dose dexamethasone and prolonged infusion time to prevent hypersensitivity reaction related to oxaliplatin in patients with colorectal cancer.
Authors: Yoshino Koichiro , Osumi Hiroki , Ooki Akira , Fukuda Koshiro , Fukuoka Shota , Nakayama Izuma , Wakatsuki Takeru , Ogura Mariko , Takahari Daisuke , Chin Keisho , Yamaguchi Kensei , Shinozaki Eiji 
Published: January 2023

49 Background: Oxaliplatin (OXA) is one of the major cytotoxic agents for the treatment of gastrointestinal tumors. Hypersensitivity reaction (HSR) is one of major reasons of not continuing OXA-based chemotherapy, similar to chemotherapy-induced peripheral neuropathy (CIPN). We developed prevention of the HSR protocol and evaluated its clinical application. Methods: We have retrospectively evaluated and characterized HSR reaction in metastatic colorectal cancer patients exposed to an OXA-containing regimen between 2005 and 2019. We also evaluated the clinical utility of a prevention of the HSR protocol for mCRC patients occurred in grade 1, grade 2 or grade 3 HSR after administration of OXA-based chemotherapy. The prevention of HSR protocol is based on increasing the dose of dexamethasone to 16.5 mg/body, chlorpheniramine to 5 mg, famotidine to 20mg, and the administration time of OXA is extended to 4 hours. Results: A total of 209 patients (median age 61 years, range: 27 to 80) were experienced grade 1 (106 patients, 50.7%), grade 2 (98 patients, 46.0%), or grade 3 HSR (5 patients, 3.3%). Most of the patients had been treated with the FOLFOX4 or modified FOLFOX6 regimen (86.6%). The median number of cycles of OXA administration until the initial onset of HSR was 11 (range: 2 to 48). 111 patients (53.1%) succeeded in OXA re-administration under the prevention of HSR protocol. The median OXA free interval was 23 days (range: 13 to 890). The median progression-free survival after OXA re-administration was 7.0 months (95%CI: 5.3 to 10.4). The reason for the prevention of HSR protocoldiscontinuation was HSR in 98 patients (46.9%), disease progression in 77 patients (36.9%) and CIPN in 17 patients (8.1%), respectively. Forty-eight patients (49.0%) had HSR during the first cycle of OXA re-administration and the median time to HSR after OXA re-administration was 14 days (95%CI 0-19). Grade 3 HSR after OXA re-administrationwere observed in only 6 patients (6.1%) and no one experienced Grade 4 or 5 HSR. Conclusions: Hi-dose dexamethasone and an increased infusion time may allow for OXA re-administration. The prevention of the HSR protocol may provide an alternative to permanent discontinuation of OXA.
IMbrave151: A phase 2, randomized, double-blind, placebo-controlled study of atezolizumab with or without bevacizumab in combination with cisplatin plus gemcitabine in patients with untreated, advanced biliary tract cancer.
Authors: El-Khoueiry Anthony B. , Ren Zhenggang , Chon Hongjae , Park Joon Oh , Kim Jin Won , Pressiani Tiziana , Li Daneng , Zhukova Lyudmila , Chen Ming-Huang , Hack Stephen Paul , Wu Stephanie , Liu Bo , Wang Yulei , Macarulla Teresa 
Published: January 2023

491 Background: VEGF blockade coupled with cytotoxic chemotherapy can promote an immune-permissive tumor microenvironment that can augment response to PD-L1 inhibition. IMbrave151 (NCT04677504) is a randomized, double-blind, global Phase II study evaluating the efficacy of atezolizumab (atezo), bevacizumab (bev) and cisplatin and gemcitabine (CisGem) as first-line treatment for patients with advanced biliary tract cancer (aBTC). Methods: Patients with previously untreated aBTC were randomized 1:1 to receive atezo (1200 mg every 3 weeks [q3w]) + bev (15 mg/kg q3w) or placebo + CisGem (cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on Days 1 and 8 q3w) for up to 8 cycles, followed by atezo (1200 mg q3w) + bev (15 mg/kg q3w) or placebo until disease progression or unacceptable toxicity. Patients were stratified by disease status, geographic region and primary tumor location. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR), disease control rate and safety. No formal hypothesis testing was performed. Results: In total, 162 patients were randomized to receive either atezo + bev + CisGem (n=79) or atezo + placebo + CisGem (n=83). Median age 63 years, Asia/Rest of World (43/57%), ECOG PS 0/1 (53/48%), intrahepatic/extrahepatic cholangiocarcinoma and gallbladder (54/19/27%), and metastatic/locally advanced stage (82/18%). The HR for PFS was 0.76 (95% CI: 0.51, 1.14). Median PFS was 8.4 months for atezo + bev + CisGem and 7.9 months for atezo + placebo + CisGem; the 6-month PFS rates were 78% and 63%, respectively. The confirmed ORR was 24% for atezo + bev + CisGem and 25% for atezo + placebo + CisGem. DOR ≥6 months was 89% for atezo + bev + CisGem vs 47% for atezo + placebo + CisGem. The incidence of Grade 3 or 4 adverse events was 73% and 74% with atezo + bev + CisGem and atezo + placebo + CisGem, respectively. Median OS is not reached. Conclusions: Both combinations of IMbrave151 showed a manageable safety profile. The aggregate of data suggests that combining atezo with bev and chemotherapy may provide clinical benefit in a subset of patients with aBTC. Follow-up is ongoing for OS. Clinical trial information: NCT04677504 .
A multicenter, single-arm, phase II study of nivolumab in patients with biliary tract cancer with a PD-L1 combined positive score ≥ 1.
Authors: Furukawa Masayuki , Ueno Makoto , Sakai Daisuke , Ouchi Kota , Hamamoto Yasuo , Aikata Hiroshi , Ozaka Masato , Tsumura Hidetaka , Tsuji Kunihiro , Kubo Shoji , Nishina Tomohiro , Katanuma Akio , Morizane Chigusa , Ikeda Masafumi , Mizuno Nobumasa , Inagaki Takashi , Shioji Kazuhiko , Furuse Junji 
Published: January 2023

533 Background: Patients with advanced biliary tract cancer (BTC) have a poor prognosis, and high unmet medical needs still exist for the treatment of this disease. Nivolumab has shown its effectiveness against multiple cancer types, especially those with PD-L1 expression. This study assessed the efficacy and safety of nivolumab in BTC patients with a combined positive score (CPS) ≥ 1 who were refractory or intolerant to the standard of care (SOC): gemcitabine, cisplatin and tegafur/gimeracil/oteracil (S-1). Methods: This was a single-arm, multicenter, open-label, prospective phase II study. Key eligibility criteria were as follows: having unresectable or recurrent BTC (intrahepatic bile duct cancer, extrahepatic bile duct cancer, gallbladder cancer, or ampullary cancer); being refractory or intolerant to SOC; having adequate hepatic, renal and hematological function; and having a CPS ≥ 1 in central assessment. Patients received nivolumab (480 mg, every 4 weeks) until disease progression, clinical deterioration, or unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the central review according to RECIST 1.1. The secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 84 patients were enrolled between Mar 11, 2020 and Mar 15, 2021, of them 12 received one regimen and 72 received two or more regimens. The median follow-up period was 6.90 months. ORR per central assessment was 10.7% (CR: 3.6%, PR: 7.1%), and ORR per investigator assessment was 15.5% (CR: 2.4%, PR: 13.1%). The median PFS per central and investigator assessment was 1.02 (95% CI 0.95–1.77) months and 2.48 (95% CI 1.87–2.83) months, respectively. The median OS was 6.90 (95% CI 5.26–9.20) months. The median duration of response per central and investigator assessment was not reached (range 2.8–13.0+) and 10.15 (range 2.0–12.8+) months, respectively. The 1-year survival rate was 25.3% (95% CI 15.4–36.4). The most frequent treatment-related adverse events were pyrexia (19.0%), pruritus (16.7%), and decreased appetite (13.1%). Conclusions: Nivolumab may have some activity with a durable response and a manageable safety profile in heavily treated BTC patients with CPS ≥ 1. Clinical trial information: JapicCTI-205097 .