tbuckley/cabot-search huggingface dataset:
The efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in resectable locally advanced lymph node-positive esophageal squamous cell carcinoma: A real world study.
Authors: Peng Ye, Aizemaiti Rusidanmu, Shuang Lin, Kun Zhou, Xuhui Wu, Bin Huang, Gongzhi Wu, Congxiong Peng, Xuyang Peng, Jianyang Ding, Mingjiang Huang, Huanming Yu, Shengxu Zhi
Journal: Journal of Clinical Oncology (2024)

e16091 Background: Many phase III clinical trials (Keynote 590, Orient 15, etc) have all proved the role of immunotherapy combined with chemotherapy in the treatment of esophageal squamous cell carcinoma. This study was designed to evaluate the efficacy and safety of immunotherapy and chemotherapy as neoadjuvant therapy for resectable locally advanced lymph node-positive esophageal squamous cell carcinoma. Methods: This is a multicenter, 2-cohort (IO+CT group &amp; CRT group), real world study. In IO+CT group, patients(pts) will receive sintilimab 200 mg once on day 1, albumin-bound paclitaxel 260g/m 2 from day 1 to 4, carboplatin 80mg/m 2 on day 1, every 21 days(Q3W) for 2 cycles. Key eligibility criteria included resectable, locally advanced lymph node-positive esophageal squamous cell carcinoma conformed by histology, and aged ≥18 years old with ECOG PS 0-1. The primary endpoint was pathologic complete response (pCR) rate. The secondary endpoints were event free survival (EFS), objective response rate (ORR), overall survival (OS) and safety. Results: From 7/2022 to 9/2023, 30 pts were enrolled in IO+CT group. In IO+CT group, among 30 pts who underwent surgery, 9 (30%) achieved pCR. 93.3% pts (28/30) achieved R0 resection. In 20 evaluable pts, 3(15%) achieved complete response (CR), 15(75%) achieved partial response (PR), 2(10%) achieved stable disease (SD). ORR and DCR were 90.0% (18/20) and 100.0% (20/20), respectively. There were no grade ≥2 treatment-related adverse events (TRAEs) appeared. The most common grade 1 TRAEs was fatigue (13.3%). Conclusions: In the real world, sintilimab plus chemotherapy used as neoadjuvant therapy in resectable locally advanced lymph node-positive esophageal squamous cell carcinoma could be effective and manageable toxicity. Clinical trial information: ChiCTR2200058565.
Symptom management through electronic patient-reported outcome (ePRO)-based intervention in patients with breast cancer treated with abemaciclib: Primary results from the LIBRA study, a phase II randomized controlled trial.
Authors: Toshimi Takano, Tetsu Hayashida, Aiko Nagayama, Yukinori Ozaki, Maiko Takahashi, Tomoko Seki, Takamichi Yokoe, Yosuke Aoyama, Rika Kizawa, Meiko Nishimura, Mari Hosonaga, Fumikata Hara, Takayuki Kobayashi, Takayuki Ueno, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2024)

11110 Background: We have developed a system using LINE, a widely-used social network service in Japan, for rapid collection of ePROs based on the PRO-CTCAE criteria. To evaluate the effectiveness of intervention through this system in reducing diarrhea frequency and enhancing quality of life (QOL) in patients treated with abemaciclib, we conducted a randomized controlled trial. Methods: Patients with hormone receptor-positive advanced breast cancer scheduled to begin abemaciclib treatment were randomized to the intervention and control arms with 1:1 ratio. The LINE-ePRO system was used to monitor symptoms daily in both arms. In the intervention arm, expert medical staffs contacted patients via phone when symptoms met certain criteria, whereas patients in the control arm received standard care. The primary endpoint was the increase in the number of defecations from baseline during 28 days. The secondary endpoints included the increase in the number of defecations from baseline during 56 days, other symptoms monitored via the LINE-ePRO system, QOL evaluated by EORTC QLQ C-30 and EQ-5D-5L, relative dose intensity (RDI), treatment interruption rate, progression-free survival (PFS), and overall survival (OS). This study (LIBRA, UMIN000045432) is funded by Eli Lilly. Results: Between Jan 2022 and Apr 2023, 60 women were enrolled and 58 (29 in each arm) were analyzed in this study. Median age was 57.5 years (range 43-80), 93% of patients were post-menopausal, 71% received abemaciclib as first-line treatment, and 74% were treated in combination with aromatase inhibitors. The increase in the number of defecations from baseline was significantly lower in the intervention arm compared to the control arm both during 28 days (0.64 vs. 1.21 per day, p=0.003) and during 56 days (0.55 vs. 1.18 per day, p=0.0004). No significant difference was observed in other symptoms between the arms. In the EORTC QLQ C-30 scales, global health status/QOL (mean score change from baseline to after one cycle of abemaciclib treatment: 0 vs. -13.5, p=0.038) and diarrhea (20.7 vs. 32.2, p=0.049) were better in the intervention arm. The treatment interruption and dose reduction rates were 41.4 and 31.0% in the intervention arm, and 31.0 and 27.6% in the control arm, respectively. The mean RDI of abemaciclib was numerically lower in the intervention arm (73.5% vs. 84.8%). Conclusions: This study is the first randomized trial to demonstrate that the intervention based on daily ePROs reduces the frequency of diarrhea in patients with advanced breast cancer treated with abemaciclib. Clinical trial information: UMIN000045432.
Overall survival outcomes of phase II GECCOR-GB trial, a multicentre trial of adjuvant adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (Cape-RT) for operated gallbladder cancer (GBC).
Authors: PRABHAT GHANSHYAM BHARGAVA, Shraddha Patkar, Vikas S. Ostwal, Reena Engineer, Manali Parulekar, Sarika Mandavkar, Sujay Srinivas, RAHUL KRISHNATRY, Shivakumar Gudi, Akhil Kapoor, Durgatosh Pandey, Swapnil Patel, Abhishek Shinghal, Alok Goel, Tapas Kumar Dora, Debashish Chaudhary, Suman Kumar Ankathi, Mahesh Goel, Anant Ramaswamy
Journal: Journal of Clinical Oncology (2024)

4124 Background: The optimal adjuvant treatment for gallbladder cancer (GBC) after surgery remains unclear. We previously reported 1 year of disease-free survival (DFS) of adjuvant gemcitabine plus cisplatin (GC) or capecitabine with concurrent capecitabine radiotherapy (Cape-RT). Here, we present the secondary endpoint of the 3-year outcomes of the GECCOR-GB study. Methods: We conducted a multicenter, open-label, non-comparative randomized phase II trial of adjuvant GC or Cape-RT in patients with resected GBC. Patients were randomized 1:1 to receive either GC (gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 6 cycles) or Cape-RT arm {Capecitabine 1000 mg/m2 BD on days 1–14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825 mg/m2 BD) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary endpoint was DFS, and the secondary endpoints were overall survival (OS), safety, and treatment completion rates. Results: We enrolled 90 patients at 3 centers in India between May 2019 and February 2022 and randomly assigned 45 patients to each arm. In the GC arm, the median age of patients was 56 (33–72) years, and 23 (51%) patients were in stage II. While in the cape-RT arm, the median age was 55 (26–69) years, with 27 (60%) patients in stage II. The 3-year DFS was 54.3% in the GC arm and 70.7% in the Cape-RT arm, respectively. The 3-year OS was 75% in the GC arm and 73% in the Cape-RT arm, respectively. The 3-year OS in stage II patients (n = 23) in the GC arm was 91.3%, while in the cape-RT arm (n = 27), it was 91.9%. Median OS in stage III patients (n = 22) was 39.1 (95% CI, 33.4–44.6) months in the GC arm, while in the cape-RT (n = 18), it was 23.2 (95% CI, 7.0–39.4) months. Conclusions: Adjuvant GC arm patients, especially those in stage III, had encouraging OS at 3 years, while both GC and adjuvant Cape-RT arms had excellent 3-year OS, reaching more than 90% in patients with stage II-operated GBC. Further studies are needed to compare and validate these findings for GBC patients. GECCOR-GBwas led by Tata Memorial Hospital (TMC), Mumbai. Clinical trial information: CTRI/2019/05/019323.
Preliminary efficacy and safety of total neoadjuvant therapy combined with PD-L1 blockade in pMMR/MSS locally advanced rectal cancer (ESTIMATE): A prospective, single-arm, phase II trial.
Authors: Xuan Zhang, Qing Feng, Xinyi Cai, Kun Yu, Tao Shen, Dingguo Pan, Jing Tan, Yunhe Ju, Lijuan Zhang, Lin Xie, Jianhua Dong, Cuifeng Xia, Wei Xiong, Quan Yang, Tao Wu, Yun-Feng Li
Journal: Journal of Clinical Oncology (2024)

e15602 Background: Patients with locally advanced rectal cancer (LARC) experience benefits from total neoadjuvant therapy (TNT). This study aims to explore the efficacy and safety of combining TNT with immunotherapy for pMMR/MSS LARC patients. Methods: ESTIMATE is a prospective, single-center, phase II study (ChiCTR2400079718) enrolling pMMR/MSS LARC patients with tumors located 10cm away from the anal margin. Treatment involved induction chemotherapy with immunotherapy ([mFOLFOX6, days 1-2 + Envafolimab 200mg, ih, day 1]; q2w; 2 cycles), long-course concurrent chemoradiotherapy (LCRT) with immunotherapy ([IMRT, 50Gy/25f, 2Gy + Cape 825mg/m2, bid]; 5w + Envafolimab 200mg, ih, day 1; q2w; 3 cycles), consolidation chemotherapy with immunotherapy ([mFOLFOX6 + Envafolimab; 2 cycles), and then total mesorectal excision (TME) 3 weeks later or watch and wait (W&amp;W). The primary endpoint is the pathological complete response (pCR) rate. Results: Until Nov. 16th, 2023, 35 patients were enrolled, with 28 completing the TNT regimen. The efficacy analysis revealed that out of 28 patients, 12 (42.9%) achieved clinical complete response (cCR), with 7 individuals choosing the W&amp;W strategy. 21 patients underwent TME, yielding 8 with a tumor regression grade (TRG) of 0, 7 with TRG of 1, and 6 with TRG of 2. The rates of pCR, major pathological response (MPR), and complete response (CR) were 38.1% (8/21), 71.4% (15/21), and 53.6% (15/28), respectively. 25 (89.3%) patients experienced treatment-related adverse events (AEs) of any grade. Non-hematological AEs included decreased appetite, fatigue, nausea, and vomiting, while hematological AEs mainly comprised thrombocytopenia, anemia, and leukopenia or neutrophilia. Grade III AEs were primarily leukopenia or neutrophilia (2/28, 7.1%). Additionally, circulating tumor DNA (ctDNA) levels were measured in 7 patients who chose the W&amp;W strategy after achieving cCR. Of these, 6 tested negative for minimal residual disease (MRD), while 1 had a positive MRD result (ctDNA: 0.56 MTM/ml). As of Jan. 26th, 2024, with a median follow-up of 5 months (range: 3-6), no recurrence was observed in any of the patients. Conclusions: The TNT approach, integrating LCRT with mFOLFOX6 and PD-L1 blockade, demonstrated a favorable CR rate and acceptable tolerability, offering a potential avenue for organ preservation in low rectal cancer patients with pMMR/MSS. Long-term benefits need validation through further follow-up. Clinical trial information: ChiCTR2400079718. [Table: see text]
Adjuvant S-1 vs. observation for resected biliary tract cancer: 5-year follow-up of the JCOG1202/ASCOT.
Authors: Kohei Nakachi, Masafumi Ikeda, Masaru Konishi, Junki Mizusawa, Hiroshi Katayama, Yusuke Sano, Katsuhiko Uesaka, Hiroaki Yanagimoto, Soichiro Morinaga, Hiroshi Wada, Kazuaki Shimada, Yu Takahashi, Toshio Nakagori, Kunihito Gotoh, Ken Kamata, Yasuhiro Shimizu, Hiroshi Ishii, Takuji Okusaka, Junji Furuse, Makoto Ueno
Journal: Journal of Clinical Oncology (2024)

4119 Background: S-1, an oral fluoropyrimidine derivative, demonstrated significant improvement in overall survival (OS) over observation in patients with curatively resected biliary tract cancer (BTC) (hazard ratio [HR] 0.694, p=0.008; the 3-year OS, 67.6% vs. 77.1%, Lancet 2023). We present updated efficacy data based on a 5-year follow-up of JCOG1202/ASCOT. Methods: Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone R0/R1 resection were randomly assigned (1:1) to undergo observation or to receive S-1 (at the dose of 40 mg/m 2 twice daily for 4 weeks, followed by 2 weeks of rest, for 4 cycles). The primary endpoint was OS, and the secondary endpoints were relapse-free survival (RFS), adverse events, and proportion of treatment completion. Results: From September 2013 to June 2018, a total of 440 patients (observation, n=222; adjuvant S-1, n=218) were enrolled. The final data cutoff date was June 23, 2023, and the median follow-up duration was 61.5 months. Of all the randomized patients, 215 (48.4%) had died (118 [53.2%] in the observation group; 97 [44.5%] in the S-1 group). The 5-year OS was 52.2% in the observation group and 64.1% in the S-1 group (stratified HR 0.723, 95% confidence interval [CI], 0.551-0.948; one-sided p=0.019). Of the 440 patients, 239 (54.3%) had RFS event (127 [57.2%] in the observation group; 112 [51.4%] in the S-1 group). The 5-year RFS was 45.9% in the observation group and 53.6% in the S-1 group (unstratified HR 0.797, 95% CI 0.618-1.028, stratified HR 0.761, 95% CI 0.589-0.984 in the sensitivity analysis). Most prespecified subgroup analyses (age, primary site, stage, lymph node metastases, types of resections, and serum CA19-9 levels) revealed favorable OS and RFS for the S-1 group. Conclusions: Adjuvant S-1 therapy maintained its survival benefit in a 5-year long-term follow-up, with clinically meaningful improvement in RFS, suggesting that it could be a standard of care for BTC. Clinical trial information: UMIN000011688.
Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238
Authors: Jeffrey Weber, Michele Del Vecchio, Mario Mandalá, Helen Gogas, Ana M. Arance, Stephane Dalle, C. Lance Cowey, Michael Schenker, Jean-Jacques Grob, Vanna Chiarion-Sileni, Iván Márquez-Rodas, Marcus O. Butler, Anna Maria Di Giacomo, Luis de la Cruz-Merino, Petr Arenberger, Victoria Atkinson, Andrew Hill, Leslie A. Fecher, Michael Millward, Nikhil I. Khushalani, Paola Queirolo, Georgina V. Long, Maurice Lobo, Margarita Askelson, Paolo A. Ascierto, James Larkin
Journal: Journal of Clinical Oncology (2024)

In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy.
Phase II study of pirfenidone combined with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer.
Authors: Guifang Guo, Shengping Li, Yize Mao, Qiuxia Yang, Zehui Yao, Jun Wang
Journal: Journal of Clinical Oncology (2024)

4152 Background: Pancreatic cancer is a disastrous malignancy characterized by the dense fibrous stroma, elevating interstitial pressure and impairing perfusion of chemotherapeutics. Pirfenidone (PFD) is an oral antifibrotic agent, which might reduce the degree of fibrosis of pancreatic cancer and increase drug delivery. Thus, we aimed to evaluate the efficacy and safety of pirfenidone (PFD) plus nab-paclitaxel and gemcitabine (AG) for patients with metastatic pancreatic cancer. Methods: In this two-stage single-arm phase II trial, treatment-naïve patients with metastatic pancreatic cancer received oral PFD, 200 mg three times daily in the first week and 400 mg three times daily thereafter, in combination with intravenously administered gemcitabine 1000 mg/m2 and nab-paclitaxel 120 mg/m2 on days 1,8 of each 21-day cycle. The primary endpoint was overall response rate (ORR). A total of 33 patients were required based on the assumption of an expected ORR of 45%, with an α-error of 5% (one-sided) and a β-error of 20%. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: We enrolled 33 patients from October 2020 to February 2023, with median age of 61years (IQR 53-65), 21(63.6%) male and 12(36.4%) female. Metastatic sites included the liver (32cases), lung(7cases) and peritoneum (11cases). The last one patient was enrolled on February 24, 2023 and the deadline of follow up was Jan 25, 2024, with only one was unevaluable. The ORR was 50.0% (95% CI 33.6%-66.4%) and the DCR was 93.8%(95%CI 79.9%-98.9%). The median PFS was 4.9 months (95% CI 3.9-5.9) and the median OS was 9.1 months (95% CI 7.8-10.4). Among all cases of 25 with elevated CA19-9 at diagnosis, 56% patients experienced a decrease in CA19-9 levels of more than 50%. Grade 3-4 toxicities were observed in 11 (34.4%) patients, with leukopenia (7[21.9%]), anemia (5[15.6%]) and elevated AST level (4[12.5%]). No treatment-related deaths occurred. Conclusions: Adding PFD to AG showed promising ORR and DCR and an acceptable adverse event in patients with metastatic pancreatic cancer. Clinical trial information: ChiCTR2000034397.
Durvalumab and tremelimumab versus doxorubicin in previously untreated patients with advanced or metastatic soft tissue sarcoma: Patient-reported outcomes (PROs) of the randomized phase II MEDISARC study (AIO-STS-0415).
Authors: Viktor Grünwald, Barbara Hermes, Armin Tuchscherer, Sebastian Bauer, Rainer Hamacher, Daniel Pink, Lars H Lindner, Stefan Gröschel, Peter Reichardt, Stephan Richter, Christoph Oing, Marinela Augustin, Martina Margrit Crysandt, Martin Kortüm, Bernd Kasper, Marc Fischer, Philipp Ivanyi
Journal: Journal of Clinical Oncology (2024)

11519 Background: The randomized phase II MEDISARC trial (NCT03317457) tested durvalumab (DUR) and tremelimumab (TRE) vs. doxorubicin (DOX) in soft tissue sarcoma (STS) patients in first-line therapy. The study showed no PFS benefit (HR 1.22; 95%CI 0,90-1.64; P = .4049), but a trend in prolonged OS (HR 0.73; 95%CI 0.54-0.99; P = .185) in favor of DUR-TRE (Grünwald et al. ESMO 2024: LBA90). The current analysis reports on patient reported outcomes (PROs) under treatment. Methods: We utilized EORTC QLQ-C30 printed questionnaires in randomized patients. PRO were assessed during screening and under treatment every 12 weeks until progression, and 4 weeks after last dose. Time to deterioration (TTD; decrease by 5 points) and mean change from baseline was measured for QLQ-C30 domains. Formal statistic testing was not performed. Results: The median follow-up for DUR-TREM vs. DOX were 34.0 mo. (25.6-42.2) and 37.9 mo. (31.5-37.9). The median duration of therapy was 2.8 (0-13) and 2.1 (0-4) mo., respectively. 86 of 92 (93.5%) patients had ≥1 PRO assessments and were included into the analyses. The completion rate at week 12 was 41.3%. Mean baseline global health status (GHS) was 54.1 (SD: 25.64) and 56.5 (SD: 28.47), respectively. GHS above the median was associated with improved OS and PFS in both arms, indicating a possible predictive biomarker. Under treatment, changes in PRO domains at 12 weeks were noted. TTD favored DUR-TRE in selected functional and symptom domains. Details will be shown at the meeting. Conclusions: MEDISARC is the first study to compare check-point inhibitor and doxorubicin treatment in sarcoma patients. PRO measures from baseline to week 12 favored DUR-TRE. Overall, results indicated better symptom and quality of life in patients treated with DUR-TRE. Clinical trial information: NCT03317457. [Table: see text]
Tislelizumab plus intensity modulated radiotherapy in resectable hepatocellular carcinoma with macrovascular invasion: A prospective, single-arm, phase II trial.
Authors: Hongyu Pan, Liuyu Zhou, Zhuo Cheng, Cheng Yang, Jin Zhang, Ningjia Shen, Hongbin Ma, Yao Li, Riming Jin, Weiping Zhou, Dong Wu, Wen Sun, Ruoyu Wang
Journal: Journal of Clinical Oncology (2024)

4118 Background: Hepatocellular carcinoma (HCC) patients (pts) with macrovascular invasion (MVI) have dismal prognosis, and limited evidence for perioperative therapies is available. This study aims to explore the safety and feasibility of perioperative tislelizumab (a PD-1 monoclonal antibody) plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Methods: This single-arm phase II trial enrolled resectable HCC pts with MVI, as assessed by the investigators before surgery. Pts were treatment-naïve, with ECOG of 0-1, and had adequate organ and bone marrow function. Eligible pts received 3 cycles of tislelizumab (200mg, d1, Q3W) and concurrent IMRT (45 Gray in 15 fractions). After surgical feasibility assessment, HCC resection is scheduled after IMRT, followed by adjuvant tislelizumab up to one year. The primary endpoints include overall response rate (ORR) and overall survival (OS). Secondary endpoints are significant pathological response (viable tumor cells &lt;10%), recurrence-free survival (RFS) and safety. Results: From Oct 21, 2020 to Feb 15, 2023, 30 pts were enrolled, with most pts 26 (86.7%) were males and 29 pts (96.7%) had HBV infection. 28 pts (93.3%) had Child-Pugh grade A and 29 pts (96.7%) had ECOG PS 0. The types of vascular invasion were main portal vein (n=9), branched portal vein (n=15), major hepatic vein (n=2), or both portal and hepatic vein (n=4). In 30 pts, ORR was 30.0% (RECIST1.1), DCR was 36.6% and the median OS was 18.7 months. 15 (50%) underwent radical surgical resection followed by adjuvant tislelizumab, 10 (66.7%) achieved a significant pathological response. By Sep 30, 2023, median RFS was not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. Of the pts who underwent surgery, 7 (46.7%) pts experienced tumor relapse with 1-year RFS rate was 60%. The most common events of any grade were increased thyroid stimulating hormone (TSH) (83.3%), leukopenia (60.0%) and anemia (53.3%). 4 (13.3%) pts experienced grade 3 TRAEs (leukopenia, increased TSH and increased alkaline phosphatase).An exploratory analysis suggests that pts who underwent surgery have longer median OS (not reached versus 7.0 months, p=0.025). AFP reduction after perioperative therapy was found to be prognostic of RFS. Conclusions: The effectiveness and tolerability of tislelizumab plus radiotherapy as perioperative therapy for resectable HCC with MVI is worth further exploration. Clinical trial information: ChiCTR2000036385.