bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant nab-paclitaxel plus S-1 versus capecitabine plus oxaliplatin for patients with stage III gastric adenocarcinoma after D2 dissection: A multicenter, open-label, randomized phase 3 study.
Authors: Pengfei Yu , Du Yian , Xu Zhiyuan , Yang Litao , Ying Jieer , Chen Ping , Wei Yunhai , Wu Yingjie , Zhang Xiaojing , Yan Zhilong , Chen Zhiheng , Xu Hongtao , Li Yong , Zheng Zhichao , Xu Nong , Cheng Xiangdong 
Published: June 2023

4054 Background: Multiple clinical studies have shown that adjuvant chemotherapy could prolong the survival of patients after radical resection, it is necessary to explore better treatment options for patients with stage III gastric adenocarcinoma (GAC). We designed this study to evaluate the efficacy and safety of adjuvant nab-paclitaxel combined with S-1 (AS) versus capecitabine combined with oxaliplatin (CAPOX) in GAC. Methods: Patients with stage III GAC after D2 radical resection and achieved R0 resection were randomized 1:1 to receive adjuvant AS (nab-paclitaxel: 100 mg/m2, d1 and 8, q3w; S-1: 40-60 mg, bid, d1-14, q3w) or CAPOX (oxaliplatin: 130 mg/m2, d1, q3w; capecitabine: 1000 mg/m2, bid, d1-14, q3w) for 8 cycles. Stratification analysis was performed according to histological type (differentiated vs undifferentiated GAC) and AJCC 8th pathological staging (ⅢA vs ⅢB and ⅢC). The primary endpoint was 3-year disease-free survival (DFS) rate, secondary endpoints were overall survival (OS) and safety. Results: Between March 20, 2020 and January 17, 2023, 313 patients were randomized to receive AS (n = 156) or CAPOX (n = 157). Baseline characteristics were generally balanced between the two groups. Median follow-up time was 5.16 months. The 1-year DFS rates were 87.14% and 70.16%, in the AS and CAPOX groups, respectively. The median DFS and 3-year DFS rates were not reached. The 1-year OS rate was 88.47% in AS group, and 63.89% in CAPOX group. At date cutoff, 12 patients (peritoneal recurrence, 1 patient; locoregional recurrence, 3 patients; distant recurrence, 8 patients) relapsed in the AS group and 16 patients (peritoneal recurrence, 4 patients; locoregional recurrence, 5 patients; distant recurrence, 8 patients; tumor marker recurrence, 1 patient) relapsed in the CAPOX group; some patients had multiple recurrence sites. 2 patients (1 patient for GAC; 1 patient for other diseases) died in the AS group and 11 patients (9 patients for GAC; 2 patients for other diseases) died in the CAPOX group. The median relative dose intensity of nab-paclitaxel was 90.32%, of S-1 was 80.77%, of oxaliplatin was 77.44% and of capecitabine was 78.55%. The incidence of adverse events (AEs) of any grade and grade 3/4 were 79.49% and 39.74% in the AS group, 72.61% and 22.93% in the CAPOX group. In the AS and CAPOX groups, neutropenia (31.63% vs 20.13%), leukopenia (29.71% vs 17.25%), anemia (27.80% vs 23.00%) and thrombocytopenia (4.15% vs 17.25%) were the most common AEs. Conclusions: Compared with CAPOX regimen, AS regimen has better survival rates and acceptable tolerability. AS provided new potential adjuvant regimen for stage III gastric cancer after D2 resection. Clinical trial information: NCT04135781 .
Predicting role of circulating tumor DNA and blood-based tumor mutational burden in esophageal squamous cell carcinoma receiving chemoradiotherapy combined with toripalimab: Exploratory analyses from a phase II trial (EC-CRT-001).
Authors: Chen BaoQing , Liu Shi-Liang , Li Qiaoqiao , Liu Mengzhong , Yang Hong , Xi Mian 
Published: June 2023

4056 Background: EC-CRT-001 is a phase II trial investigating the efficacy of toripalimab (an anti-PD1 antibody) combined with definitive chemoradiotherapy (CRT) in locally advanced esophageal squamous cell carcinoma (ESCC) and the results demonstrated encouraging antitumor activity and acceptable toxicity. This exploratory analysis was performed to evaluate the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) for efficacy prediction. Methods: Forty-two patients from the phase II trial (NCT04005170) who received toripalimab (240 mg every 3 weeks for up to 1 year, or disease progression, or unacceptable toxicity) combined with definitive CRT (irradiation with 50.4 Gy in 28 fractions concurrent with 5 cycles of weekly paclitaxel in 50 mg/m2 and cisplatin in 25 mg/m2) were enrolled. Plasma samples were collected before, during, and after CRT. Targeted next-generation sequencing was performed on a total of 118 plasma samples and 35 matched tumor samples using a panel covering 474 cancer-associated genes. Results: Twenty-six (62%) of 42 patients achieved clinical complete response (cCR) at three months after CRT. ctDNA was detected in 29 (72.5%) of 40 patients at baseline. The positive rate of ctDNA decreased to 43.9% (20/41) during CRT and continued to descend to 27.0% (10/37) at the completion of CRT. A higher cCR rate was observed in patients with negative during-CRT ctDNA compared to those with detectable ctDNA (82.6% vs. 38.9%, P = 0.008). Patients with post-CRT detectable ctDNA also had poorer cCR rate (30.0% vs. 77.8%, P = 0.017). Within a median follow-up of 24.0 months (IQR 13.7-27.9), the median progression-free survival (PFS) was 12.2 months (95%CI: 8.4-16.0) and median overall survival (OS) was not reached for the whole cohort. Patients with during-CRT detectable ctDNA had shorter PFS compared to ctDNA-negative patients (HR = 2.57, 95%CI: 1.18-5.60, P = 0.014). Similarly, patients with post-CRT detectable ctDNA also had a significantly increased risk of disease progression (HR = 2.88, 95%CI: 1.21-6.83, P = 0.012) and death (HR = 3.67, 95%CI: 1.41-9.55, P = 0.004). Moreover, patients with higher bTMB ( > 1) detected during CRT were associated with a favorable OS (HR = 0.33, 95%CI: 0.13-0.88, P = 0.027). Improved PFS was also observed in those patients with higher post-CRT bTMB ( > 3) (HR = 0.28, 95%CI: 0.08-0.96, P = 0.042). Conclusions: Negative ctDNA status and higher bTMB during or after CRT were associated with better tumor response and favorable survival in ESCC patients who underwent definitive CRT combined with toripalimab. Dynamic ctDNA has great potential in predicting efficacy and risk of disease progression in ESCC. Clinical trial information: NCT04005170 .
Pembrolizumab, radiotherapy, and chemotherapy in neoadjuvant treatment of malignant esophago-gastric diseases (PROCEED): Assessment of pathologic response and toxicity in a prospective, phase II single-arm trial.
Authors: Karukonda Pooja , Czito Brian G. , Duffy Eileen , Uronis Hope Elizabeth , D'Amico Thomas A. , Strickler John H , Niedzwiecki Donna , Willett Christopher , Palta Manisha 
Published: June 2023

4062 Background: A standard treatment paradigm for locally advanced, resectable, non-metastatic esophageal or gastric adenocarcinomas (EGA) is neoadjuvant chemoradiation (CRT) followed by surgery. Historical pathologic complete response (pCR) rates after CRT with carboplatin/paclitaxel in the CROSS trial are low at 23%. Efficacy of adjuvant immunotherapy has since been shown in this patient population. The main objectives of this trial were to investigate whether neoadjuvant CRT + pembrolizumab improves pCR compared to the historical control of CRT alone, and also determine the associated acute and post-surgical toxicity of this approach. Methods: Single-institution, prospective phase II trial (NCT03064490) evaluating the efficacy and safety of neoadjuvant pembrolizumab + CRT followed by adjuvant pembrolizumab in patients with locally advanced operable EGA. CRT (45 Gy/25 fractions with concurrent weekly carboplatin [AUC 2] and paclitaxel [50 mg/m2 of BSA]) with 3 cycles of pembrolizumab was administered as neoadjuvant therapy. Patients also received 3 cycles of adjuvant pembrolizumab after surgical resection if they did not experience ≥Grade 3 (G3) toxicity during neoadjuvant treatment. Baseline characteristics were collected. Pathologic response was scored from 0-3 per tumor regression grading. The percentage of patients with pCR (score of 0) are described. Acute toxicities are defined per CTCAE v4 and include relevant events occurring within 90 days after treatment. Results: Accrual is complete, with 35 patients with cT2-3N0-2M0 EGA enrolled from 10/10/2017-10/07/2022. 28/32 patients have completed neoadjuvant therapy and surgical resection. 89% of enrolled patients are male, and 94% are white. 97% have an esophageal primary, and 97% underwent R0 resection. 10/28 (35.7%: 95% CI: 17%, 53%) patients achieved a pCR. 22/32 patients have experienced treatment-related ≥G3 non-hematologic toxicity to date (94.2% G3, 5.8% G4). 18 patients experienced ≥G3 toxicity related to neoadjuvant therapy, with 53 events overall, the majority being GI (24.5%) or metabolic/nutritional disorders (24.5%). 10 patients experienced ≥G3 toxicity related to surgery, with 16 events overall, the majority being procedural complications (31.3%) and infectious disorders (31.3%). Conclusions: Patients undergoing neoadjuvant CRT + pembrolizumab for EGA experienced higher rates of pCR and acceptable rates of treatment-related toxicity compared to historical controls. This phase II trial demonstrates the safety and efficacy of this treatment paradigm, which warrants assessment in future prospective studies. Clinical trial information: NCT03064490 .
Five-year overall survival with S-1 plus docetaxel as adjuvant treatment in curatively resected pStage III gastric cancer in JACCRO GC-07.
Authors: Ichikawa Wataru , Yoshida Kazuhiro , Kodera Yasuhiro , Kitazawa Masato , Hirao Motohiro , Seto Yasuyuki , Hibi Kenji , Kinami Shinichi , Watanabe Masaya , Makino Shigeto , Kochi Mitsugu , Sano Takeshi , Kakeji Yoshihiro , Takeuchi Masahiro , Fujii Masashi 
Published: June 2023

4065 Background: JACCRO GC-07 is a randomized controlled trial to explore postoperative S-1/docetaxel compared to S-1 alone after D2 gastrectomy for pStage III gastric cancer (GC) patients. The second interim analysis demonstrated that the significant improvement of RFS was obtained by S-1/docetaxel compared to S-1 alone. The study was terminated by the recommendation of independent data and safety monitoring committee (Yoshida K et al. J Clin Oncol 2019; 37:1296-1304). Preplanned analysis to evaluate RFS at 3 years, the primary endpoint, was also published (Kakeji Y et al. Gastric Cancer 2022; 25:186-196). We report the 5-years follow-up data from the trial. Methods: Patients with pStage III GC were randomly assigned to receive either S-1/docetaxel (S-1 80-120mg/body on days 1-14 with a 7-day rest followed by docetaxel 40mg/m2 on day 1 and S-1 80-120mg/body on days 1-14 every 21 days for 6 cycles followed by S-1 80-120mg/body on days 1-28 every 42 days for 4 cycles) or S-1 (80-120mg/body on days 1-28 every 42 days for 8 cycles) after D2 gastrectomy. Blocked randomisation was performed and stratified by the stage (IIIA, IIIB, IIIC) and histological type (differentiated or undifferentiated). The primary endpoint was 3y RFS and the secondary endpoints were OS, TTF and safety. This analysis presents the final preplanned assessment of outcomes after 5 years. Results: Of 915 randomly assigned patients, 912 patients were included in the intention-to-treat (ITT) analysis. In the final analysis, 426 recurrences and 373 deaths were confirmed among the ITT population during the median follow-up period of 63.72 months (3.52-111.87). The 5y RFS of 59.8% in the S-1/docetaxel group was significantly superior to 50.6% in the S-1 group (HR 0.726, 95% CI: 0.599-0.879, p = 0.0010) and the 5y OS was 67.9% in the S-1/docetaxel group and that of S-1 group was 60.3%, respectively (HR 0.752, 95% CI: 0.613-0.922, p = 0.0059), confirming the significant improving effect on the survival of the patient. Conclusions: Adjuvant treatment with S-1 plus docetaxel should be considered for patients with pStage III gastric cancer who underwent D2 gastrectomy without neoadjuvant chemotherapy. Clinical trial information: UMIN000010337 .
Neoadjuvant docetaxel, oxaliplatin, and s-1 plus surgery and adjuvant s-1 for resectable advanced gastric cancer: Final survival outcomes of the randomized phase 3 PRODIGY trial.
Authors: Kang Yoon-Koo , Kim Hyung-Don , Yook Jeong Hwan , Park Young-Kyu , Kim Young-Woo , Kim Jin Young , Ryu Min-Hee , Rha Sun Young , Chung Ik-Joo , Kim In-Ho , Oh Sang Cheul , Yoo Chang Hak , Kang Seok Yun , Zang Dae Young , Kim Sunju , Noh Sung Hoon 
Published: June 2023

4067 Background: The phase 3 PRODIGY study compared neoadjuvant docetaxel, oxaliplatin and S-1 (DOS) chemotherapy followed by surgery followed by adjuvant S-1 with surgery followed by adjuvant S-1 for Korean patients with resectable locally advanced gastric cancer (LAGC) (Kang et al. J Clin Oncol. 2021). The planned analysis of the primary endpoint of PRODIGY showed that the addition of neoadjuvant DOS to surgery and adjuvant S-1 improved progression-free survival (PFS). We herein report the long-term follow-up outcomes, including overall survival (OS), from this trial. Methods: Patients with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma with clinical T2-3N+ or T4Nany disease were enrolled from 18 Korean study sites. Patients were randomly assigned to D2 surgery followed by adjuvant S-1 (40–60 mg orally twice a day, days 1–28 q6w for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1–14 q3w for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary endpoint was PFS. OS was the secondary endpoint. This analysis presents the final assessment of the outcomes after 5 years. Results: A total of 266 and 264 patients were randomly assigned to the CSC and SC arms, respectively, among which 238 and 246 patients were treated and included in the full analysis set. As of the data cut-off date (SEP-2022), the median follow-up duration of the surviving patients was 99.5 months (range, 68.6–127.7 months). As compared to SC, CSC significantly increased the OS (adjusted hazard ratio, 0.72; 95% CI, 0.54 to 0.97; stratified log-rank P=0.028) with a 5-year OS rate of 66.8% and 63.0% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (adjusted hazard ratio, 0.71; 95% CI, 0.53 to 0.94; stratified log-rank P=0.019) with a 5-year PFS rate of 60.6% and 56.9% for the CSC and SC arms, respectively. Conclusions: The addition of neoadjuvant docetaxel, oxaliplatin and S-1 (DOS) chemotherapy, as part of perioperative chemotherapy, to surgery and adjuvant S-1 prolonged the OS and PFS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1 alone. Neoadjuvant DOS chemotherapy should be considered one of the standard treatment options for patients with LAGC in Asia. Clinical trial information: NCT01515748 .
Neoadjuvant tislelizumab combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Single arm phase II study.
Authors: Jin Peng , Gao Yong sheng , Fu Zheng , Yang Wen feng , Meng Xue 
Published: June 2023

4068 Background: This study aimed to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. Methods: This is a prospective single-arm clinical trial. A total of 20 patients with newly diagnosed resectable esophageal cancer (cT1-2N+ / cT3-4aN0-3 M0) received 2 cycles of tislelizumab (200mg every 3 weeks for 2 cycles) concurrent with chemoradiotherapy (radiotherapy: 41.4Gy in 23 fractions; chemotherapy: Paclitaxel (Albumin bound) 100mg/m2, and Cisplatin 75 mg/m2 once every 3 weeks for 2 cycles.) Radical esophagectomy was performed within 4-6 weeks after neoadjuvant therapy. PET/CT was performed at baseline and before surgery. Primary endpoints included pathological response rate (pCR) and major pathological response rate (MPR), the secondary endpoints were disease free survival and safety. Exploratory endpoints include molecular imaging research and immune biomarker to further explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. Results: Twenty patients enrolled, all of whom received neoadjuvant tislelizumab combined with chemoradiotherapy. Eighteen patients underwent radical esophagectomy. One patient underwent radical chemoradiotherapy due to lymph node metastases after neoadjuvant therapy. One patient died of pneumonia before surgery. Among 18 patients who underwent surgery, R0 was 100% (18/18), 9 patients achieved pCR (50.0%), and 13 patients achieved MPR (72.2%). Most of treatment-related adverse event (TRAE) were grade 1-2, and the most common TRAE was anemia (15, 75.0%). The grade 3 TRAE included 1 leukopenia (5.0%), 1 neutropenia (5.0%), 1 liver damage (5.0%), and 1 elevated cardiac troponin T (5.0%). A significant decrease in SUVmax was observed in both pCR and no-pCR patients after treatment. Baseline SUVmax in no-pCR patients tended to be higher than pCR patients(p=0.0642). Furthermore, a significant increase in circulating CD4+ T cells, CD4+ effector memory T cells (TEM), and M1 were found after treatment. Among the patients with pCR, the CD4+ TEM and cDCs after treatment were higher than those in the no-pCR patients, while Tregs and M2 were lower. Conclusions: Neoadjuvant tislelizumab combined with chemoradiotherapy for locally advanced ESCC has promising efficacy and good safety. Clinical trial information: NCT05323890 . [Table: see text]
Transarterial chemoembolization combined with lenvatinib and camrelizumab for unresectable hepatocellular carcinoma: A prospective, single-arm, multicenter study.
Authors: Zhang Zhibo , Yan Maolin , Chen Yufeng , Wu Xukun , Yang Lanfang , Yin Zhengyu , Lu Hao , Zeng Yongyi , Zhang Hui , Huang Jingyao , Chen Jiafei , Wang Liang , Chen Zhongwu 
Published: June 2023

4072 Background: Conversion therapy for unresectable hepatocellular carcinoma (uHCC) has attracted increasing interest in recent years. In 2020 ASCO annual meeting, one abstract reported that the combination therapy of tyrosine kinase inhibitor and anti-PD-1 antibody could be a promising conversion therapy for patients with initially uHCC. This study aims to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and camrelizumab (TACE+LEN+CAM) as a conversion therapy for uHCC. Methods: This single-arm, prospective, multicenter study was conducted on patients diagnosed with HCC (with an Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1 and Child-Pugh class A) who were ineligible for surgery. Enrolled patients received camrelizumab (200 mg every 3 weeks) and lenvatinib (bodyweight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) after TACE treatment. Surgery was performed after treatment response was assessed to meet the criteria of resection. Patients who did not meet the criteria for surgery continued to receive triple treatment until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR)and safety. Secondary endpoints included percentage of patients amendable to surgery, the rate of radical (R0) resection, disease control rate (DCR). This study is registered with Chinese Clinical Trial Registry (ChiCTR2100050410). Results: Between Oct 25, 2021, and Jul 20, 2022, 55 patients were enrolled and received triple therapy (TACE+LEN+CAM). Of these, 37 (67.3%) patients had portal vein tumor thrombosis. Mean tumor diameter for all patients was 112 ± 83 mm. 52 (94.6%) patients with≤2 target lesions, and 3 (5.4%) patients with > 2 target lesions. As of data cutoff on Dec 20, 2022, the median follow-up was 6.7 months (IQR 5.0-9.89). According to modified RECIST criteria, tumor response in patients included complete response to treatment in 9 patients (18.0%), partial response in 27 (54.0%), stable disease in 6 (12.0%), and progressive disease in 7 (14.0%). The ORR was 72.0%, and the DCR was 84.0%. 26 patients underwent surgery after successful conversion therapy. The MPR and pCR rates in the surgery population were 69.2% and 23.1%, respectively. The conversion rate was 55.3% and the R0 resection rate was 100%. 23 (41.8%) of 55 patients had treatment-related adverse event (TRAEs) that were grade 3-5. No grade 3-5 TRAEs occurred after surgery. Conclusions: The triple therapy (TACE+LEN+CAM) significantly improved ORR and the surgical conversion rate of uHCC patients with a manageable safety. Future large-scale randomised trials are warranted. Clinical trial information: ChiCTR2100050410 .
Temporal patterns of immune-mediated adverse events (imAEs) with tremelimumab (T) plus durvalumab (D) in the phase 3 HIMALAYA study in unresectable hepatocellular carcinoma (uHCC).
Authors: Lau George , Sangro Bruno , Crysler Oxana V. , Sukeepaisarnjaroen Wattana , Lipatov Oleg , Morimoto Manabu , Archambeaud Isabelle , Burgio Valentina , Tuyet Phuong Le Thi , Chao Yee , Peron Jean-Marie , Berres Marie-Luise , Ko Yoo-Joung , McCoy Carrie L. , Gupta Charu , Makowsky Mallory , Negro Alejandra , Abou-Alfa Ghassan K. 
Published: June 2023

4073 Background: In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single T Regular Interval D) significantly improved overall survival versus sorafenib (S) and had manageable safety (Abou-Alfa et al. NEJM Evid 2022). STRIDE is approved for uHCC in the United States and Japan and is recommended for approval by the European Medicines Agency. In this exploratory post hoc analysis, we assessed temporal patterns of imAEs for the STRIDE regimen in HIMALAYA. Methods: Safety was assessed in participants (pts) who received ≥1 dose of STRIDE (T 300 mg [one dose] plus D 1500 mg once every 4 weeks) or S (400 mg twice daily). Treatment causality was investigator-assessed. imAEs were defined as AEs of special interest associated with drug exposure and consistent with an immune-mediated mechanism of action for which no alternate etiology was clear. Safety was summarized descriptively overall and at specific time points after the start of treatment. Results: In total, 388 (STRIDE) and 374 (S) pts were included in the safety analysis. Median (range) duration of exposure was 5.5 (0.4–41.9) months for STRIDE (D exposure in STRIDE) and 4.1 (0.1–38.6) months for S. Any grade treatment-related AEs (TRAEs) and Grade 3 or 4 TRAEs were less frequent for STRIDE (75.8% and 25.8%, respectively) versus S (84.8% and 36.9%, respectively). Any grade imAEs and max Grade 3 or 4 imAEs occurred in 35.8% and 12.6% of pts, respectively for STRIDE. Any grade imAEs and max Grade 3 or 4 imAEs with STRIDE occurred at all time points assessed and were most likely to occur within the first three months after treatment. For STRIDE, any grade imAEs of gastrointestinal disorders and skin and subcutaneous tissue disorders were most common within the first month after treatment (3.9% and 3.1%, respectively), whereas any grade imAEs of endocrine disorders were most common between >1 and ≤2 months (6.7%). Conclusions: In HIMALAYA, AEs with STRIDE were manageable and generally low grade. Any grade TRAEs and Grade 3 or 4 TRAEs were less frequent for STRIDE versus S. Although imAEs with STRIDE could occur at any time, most were observed within the first three months after treatment. These findings continue to support STRIDE for the treatment of uHCC. Clinical trial information: NCT03298451 . [Table: see text]