tbuckley/cabot-search huggingface dataset:
Real-world evidence of FOLFIRI combined with anti-angiogenesis inhibitors or anti-EGFR antibodies for patients with early recurrence colorectal cancer after adjuvant FOLFOX/CAPOX therapy in Japan: A retrospective observational study using administrative database.
Authors: Yu Sunakawa, Chaochen Wang, Yongzhe Piao, Long Jin, Yoshinori Tanizawa, Zhihong Cai, Yoshinori Kagawa
Journal: Journal of Clinical Oncology (2024)

110 Background: Oxaliplatin-containing regimens (FOLFOX or CAPOX) are the most common adjuvant treatments after curative resection of colorectal cancer (CRC). However, real-world evidence (RWE) of treatment sequence/outcomes for patients with early recurrence CRC after receiving adjuvant chemotherapy are limited. Methods: This retrospective cohort study was based on an administrative database in Japan. The primary objective was to describe the treatment sequence for patients with early recurrence CRC and treated by combination of FOLFIRI and anti-angiogenesis inhibitors (AAIs) or anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) after adjuvant FOLFOX or CAPOX therapy. The study included patients with CRC who underwent surgical resection, started adjuvant chemotherapy ≤3 months (mo) after the first surgery, had early recurrence of CRC (defined as initiation of FOLFIRI + AAIs/anti-EGFR mAbs second line [2L] regimen) within 1 year after adjuvant chemotherapy ended. Patient characteristics at baseline of 2L (60 days prior to 2L initiation) and treatment sequence were summarized descriptively; time to discontinuation (TTD) for adjuvant and 2L therapy were analyzed using Kaplan-Meier method. Cox proportional hazard model was used to identify risk factors associated with TTD of 2L regimen. Results: The cohort included 832 patients: median (range) age was 67 (24-86) years, 56.4% males, 65.5% with left-sided CRC. Most patients received CAPOX (71.3%) as adjuvant therapy. Median (95% CI) duration of adjuvant therapy was 5.4 mo (5.3-5.5). As 2L therapy, 72.5% and 27.5% of patients received FOLFIRI + AAIs (AAIs group) and FOLFIRI + anti-EGFR mAbs (anti-EGFR group), respectively. Median TTD (95% CI) of the AAIs and anti-EGFR groups in 2L were 6.2 mo (5.8-6.9) and 6.1 mo (5.2-7.4), respectively. Among patients with recurrence within 6 mo (72.6%), the median TTD (95% CI) for AAIs and anti-EGFR groups were 6.1 mo (5.5- 6.5) and 5.8 mo (5.1-7.8), respectively. Among patients with recurrence during 6 to 12 mo (27.4%), the median TTD (95% CI) of AAIs and anti-EGFR groups were 8.1 mo (6.1-9.2) and 6.2 mo (4.6-8.0), respectively. Age ≥70 years was negatively associated with TTD of 2L, HR = 1.19 (95% CI: 1.02-1.39); p=0.03. Conclusions: This is the first RWE based on administrative data on treatment sequence/ outcomes for patients with early recurrence CRC treated by FOLFIRI + AAIs/anti-EGFR mAbs after adjuvant FOLFOX/CAPOX therapy in Japan. The treatment outcomes for patients with early recurrence CRC were similar to previous clinical trials in 2L advanced CRC. The results suggested that these two 2L regimens had similar TTD; however, the timing of relapse may influence the efficacy of AAIs and anti-EGFR mAbs.
Neoadjuvant botensilimab plus balstilimab in resectable mismatch repair proficient and deficient colorectal cancer: NEST-1 clinical trial.
Authors: Pashtoon Murtaza Kasi, Mehraneh D. Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana Nguyen, Despina Siolas, Brandon Swed, Sahrish Khan, Madeleine Wood, Allyson J. Ocean, Elizabeta C. Popa, Kelly A. Garrett, Encouse Golden, Preethi Guniganti, Xi K. Zhou, Alessio Pigazzi, Manish A. Shah, Erika Hissong, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2024)

117 Background: There is an unmet need to have an effective systemic immunotherapeutic option for patients with mismatch repair proficient/microsatellite stable (pMMR/MSS) colorectal cancer. The neoadjuvant platform presents an ideal setting as a window of opportunity to evaluate new drugs. The NEST-1 trial explored the safety and efficacy of neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti–CTLA–4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in patients with colon and rectal cancer who were candidates for surgery. Methods: NEST-1, was a single-arm trial testing the feasibility, safety, and efficacy of the BOT/BAL regimen in neoadjuvant settings for patients with colorectal cancer before resection. All patients received 1 fixed dose of 75 mg of BOT and 2 fixed doses of 240 mg of BAL 2 weeks apart. Patients could proceed to surgery 1 week after completion of the 2 nd dose of BAL. Less than 25% of patients were allowed to be mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H). Other inclusion and exclusion criteria were in accordance with ongoing immunotherapy-based clinical trials. Results: The study met its primary endpoints. A total of 12 patients with colon and rectal cancers were safely treated with the BOT/BAL combination without delaying surgery or increasing the risk of any severe adverse events. Significant regression of tumors was noted (Table). Spatial biology analyses on pre-treatment biopsy and post-treatment surgical samples using RareCyte Inc. revealed novel mechanisms of action and patterns of response/regression; most of the viable tumor if present was superficially oriented near the luminal surface. ctDNA reductions correlated with pathological responses. Conclusions: BOT/BAL appears to be a safe and active regimen both in pMMR/MSS and dMMR/MSI-H colon as well as rectal cancers. The downstaging observed may spare surgery and/or adjuvant chemotherapy. Given the findings, the study has now expanded to two additional cohorts that are now enrolling to study further the dosing, and timing and/or need for surgery in these patients. Clinical trial information: NCT05571293 . [Table: see text]
Short-term outcomes of pedicled jejunum reconstruction after esophagectomy for esophageal cancer.
Authors: Mamoru Matano, Kengo Kanetaka, Shinichiro Kobayashi, Kazuma Kobayashi, Yusuke Inoue, Akihiko Soyama, Tomohiko Adachi, Susumu Eguchi
Journal: Journal of Clinical Oncology (2024)

369 Background: The number of patients with esophageal cancer after gastrectomy and patients accompanied with simultaneous gastric cancer has gradually increased because of the prevalence of gastric in Japan. Pedicled jejunum is one of the choices for esophageal reconstruction when the stomach is not available. However, surgical outcomes of jejunal reconstruction and the effect of the timing of gastrectomy remain to be elucidated. Methods: This study was a retrospective, cohort study that included 24 patients who underwent supercharged pedicled jejunal conduit for esophageal reconstruction in our institution between May 2007 and July 2023. The patients were divided into two groups: gastrectomy was performed before esophagectomy (A group) and gastrectomy was performed simultaneously for accompanied gastric cancer (S group). Surgical outcomes and postoperative complications were compared between the two groups. As a nutritional assessment, perioperative change in body composition such as visceral fat area (VFA) with computed tomography was analyzed. Results: In 24 patients, the median operative time was 769 minutes and the median blood loss was 543 g. Severe postoperative complications developed in 6 cases (25%). The A group included 15 cases and the S group did 9 cases. There was no statistical difference in postoperative complication between the two groups, however, postoperative hospital stay was statistically longer in the S group than in that of the A group (37 days vs. 21 days, p=0.02). Although weight loss at 1 year after operation was almost identical in the two groups, the loss of VFA was more severe in the S group than in the A group (23 % of preoperative VFA vs. 77% of preoperative VFA, p=0.03). Conclusions: The use of a pedicled jejunal conduit after esophagectomy could be performed safely. Postoperative nutritional support is needed for patients especially those who underwent simultaneous gastrectomy.
Updated pooled analyses of first-line anti-PD1/PD-L1 inhibitors plus chemotherapy in advanced esophageal squamous cell carcinoma.
Authors: Maysa Vilbert, Jonathan N Priantti, Thiago Madeira, Francisco Cezar A Moraes, Alireza Tojjari, Ibrahim Halil Sahin, Ludimila Cavalcante, Anwaar Saeed
Journal: Journal of Clinical Oncology (2024)

366 Background: Advanced and metastatic esophageal squamous cell carcinoma (ESCC) patients have limited treatment options and poor prognosis. Recently, several studies demonstrated the clinical benefit of combining immune checkpoint inhibitors (ICI) and chemotherapy (CT), leading to its approval in the first-line setting. Since then, efforts have been made to identify the patients who may benefit the most or not from the combination of ICI plus CT. Methods: We searched PubMed, Scopus, and the Cochrane Library for randomized clinical trials investigating first-line ICI plus chemotherapy (CT) for advanced or metastatic ESCC patients. Outcomes of interest included: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and OS according to gender, PD-L1 expression (&lt;1% / ≥1%), and PD-L1 CPS (&lt;10 / ≥10). We used I 2 statistics to assess heterogeneity, and the fixed-effect model was used to pool studies. Results: Eight studies were included with 4,702 patients. Of them, most had an ECOG 0 or 1, and were younger than 65 years (62%), male (77%), and Asian (78%). Metastatic disease was diagnosed in 75% of patients. ICI plus CT was administered to 58%, and 43% received CT +/- placebo. Median follow-up ranged from 7.1 to 22.6 months. ICI plus CT significantly improved all efficacy outcomes compared to CT alone: decreasing the risk of death by 32% (HR for OS: 0.68; 95%CI 0.63-0.74; p&lt;0.00001); reducing the risk of progression or death by 38% (HR for PFS: 0.62; 95%CI 0.58-0.67; p&lt;0.00001); and increasing the objective response rate (risk difference: 0.17; 95%CI 0.14-0.20; p&lt;0.00001). A survival benefit was seen across all subgroup analyses, but it was significantly higher in patients with PD-L1 ≥1% compared to those with PD-L1 &lt;1% (reduction in the risk of death of 38% versus 23% respectively, p=0.03). OS was not significantly different between males versus females, or PD-L1 CPS≥10 versus CPS&lt;10. Conclusions: Our large systematic review and meta-analysis support the efficacy and survival benefit of ICI plus CT as first-line therapy for all ESCC patients, regardless of gender or PD-L1 expression.
Continuation rather than early induction in S-1 adjuvant chemotherapy and prognosis in patients after biliary tract cancer resection.
Authors: Kotaro Hayashida, Tomohiko Adachi, Hajime Imamura, Manpei Yamashita, Hanako Tetsuo, Hajime Matsushima, Takanobu Hara, Akihiko Soyama, Kengo Kanetaka, Susumu Eguchi
Journal: Journal of Clinical Oncology (2024)

474 Background: The efficacy of S-1 monotherapy as adjuvant chemotherapy (AC) for pancreatic cancer has been demonstrated, and the long-term results are clearly improving. 1 In biliary tract cancer, the JCOG1201 trial in Japan also demonstrated the usefulness of S-1 AC recently. 2 We have been also performed S-1 AC for biliary tract cancer in recent years in accordance with the clinical necessity. In this article, we herein retrospectively analyze the S-1 AC for biliary tract cancer especially in the significance of initiation day or therapy continuation. Methods: 134 patients with the resection of biliary tract cancer (intrahepatic cholangiocarcinoma 25/ hilar 17/ gallbladder 27/ distal bile duct 38/ papillary 25 from January 2017 to December 2021 were included in this study. Age 73(30-87) years, 47 hepatic resections/66 pancreatecticoduodenectomies/21 peri-gallbladder resection. The decision to administer AC was made at the discretion of the attending doctor and in consultation with the patient, and the decision to discontinue was based on the patient's physical condition. If there was no particular need to discontinue, the treatment was continued for six months at least. Results: S-1 AC was performed in 57/137 (43%) of eligible patients. Age was similar between with or without AC patients (73 vs. 73 years old). There were no significant differences by the cancer location. Although pathological stage was higher in the patients with AC (stage 0:1:2:3:4 = 0: 20: 39: 31: 9%) than without AC ( = 9: 45: 33: 10: 3%) (p &lt; 0.001), 2 years recurrence free survival (2y- RFS) was similar between with AC or without AC patients (66.6 vs 71.6%, p=0.82). In the subgroup analysis of the patients with AC, although comparisons of induction day of AC within or after postoperative 6 weeks showed no difference in patient’s prognosis, patients with continuation of AC for at least 6 months after initiation clearly had a better prognosis than without it (2y-RFS: 89.6 vs 41.7%, p=0.003). Conclusions: In S-1 AC for the patients after biliary tract cancer resection, early induction does not play much role, but continuation is important to maintain better prognosis. 1. Uesaka et al. Lancet, 2016. 2. Nakachi et al. Lancet, 2023.
Tinengotinib (TT-00420) in combination with atezolizumab in Chinese patients (pts) with biliary tract carcinoma (BTC): Preliminary efficacy and safety results from a phase Ib/II study.
Authors: Panpan Zhang, Jifang Gong, Zuoxing Niu, Ying Cheng, Jean Fan, Peng Peng, Caixia Sun, Hui Wang, Yingying Yu, Yujia Zhu, Yingtong Wu, Qing Li, Peng Huang, Frank Wu, Lin Shen
Journal: Journal of Clinical Oncology (2024)

473 Background: Programmed Cell Death Ligand 1 (PD-L1) inhibitor durvalumab in combination with gemcitabine and cisplatin has been approved as first-line therapy for BTC. However, the efficacy of subsequent standard of care is limited. Tinengotinib is a spectrum-selective multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus kinases and receptor tyrosine kinases (FGFRs and VEGFRs). Tinengotinib combined with PD-L1 has demonstrated promising antineoplastic activity in preclinical study. Here we present the preliminary data of tinengotinib in combination with atezolizumab (atezo) in pts with advanced BTC from a phase Ib/II trial in China. Methods: In combination therapy, eligible pts with advanced/metastatic BTC were enrolled and treated with tinengotinib plus atezo 1200 mg/20 mL in 21-day cycle. Dose escalation (Phase Ib) and dose expansion (Phase II) were designed. Dose escalation followed a standard 3+3 design. Primary objectives in phase Ib were safety, tolerability, and determination of the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Results: As of 17-Aug-2023, six pts (5 cholangiocarcinoma, 1 gallbladder carcinoma) were enrolled and treated with tinengotinib 8 mg QD plus atezo (n=3) or tinengotinib 10 mg QD plus atezo (n=3). Median age was 62.0 years (range 47-75), 83.3% had ECOG performance status of 1, 83.3% had stage IV disease, 50% had ≥ 3 lines of prior antineoplastic therapies, and 50% had prior immunotherapy. No DLT was observed in these two dose levels. Treatment-related adverse events (TRAEs) were reported in 6 (100%) pts, including Grade (Gr)1-2 for 6 pts, Gr 3 in 2 pts. No Gr 4-5 TRAE. The most common TRAEs (≥ 50%) included hypertension, palmar-plantar erythrodysesthesia syndrome, blood bilirubin increased, proteinuria, hypertriglyceridemia and platelet count decreased. Two pts achieved partial response (PR). One prior immunotherapy naïve pt had a tumor reduction of 48.0% lasting for more than 5 months (tinengotinib 8 mg QD plus atezo). Another pt with prior immunotherapy (sintilimab), target therapy (donafenib) and chemotherapy had a tumor reduction of 39.1% (tinengotinib 10 mg QD plus atezo). Three pts had stable disease (SD). Conclusions: Tinengotinib in combination with atezo was well-tolerated for the treatment of Chinese BTC pts. Preliminary encouraging efficacy of tinengotinib in combination with atezo was observed in pts with heavily pre-treated BTC. The ongoing study is to further evaluate the safety and efficacy of tinengotinib in combination with atezo in pts with BTC who had prior immunotherapy and/or chemotherapy. Clinical trial information: NCT05253053 .
Efficacy and safety of surufatinib in biliary tract cancer: Preliminary results of a real-world study.
Authors: Zongli Zhang, Changlin Ma, Enshan Li, Yanchao Gao, Guangjian Bao, Jun Lu, Kejian Sun, Xu Zhou, Qiang He, Yunfei Xu, Kangshuai Li, Faji Yang
Journal: Journal of Clinical Oncology (2024)

486 Background: When applied in the second-line treatment for biliary tract cancer (BTC) pts, surufatinib (a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) monotherapy has demonstrated moderate clinical efficacy and has demonstrated favorable tolerability and safety profiles. This study was to evaluate the efficacy and safety of surufatinib as a therapy for BTC in a real-world setting. In particular, pts who received resection for BTC with positive margins would be eligible for this study. This population indicates a poor prognosis, for their tumor environment is complex, which is an obstacle to R0 resection. However, no proper treatment for this population has been recommended yet. Methods: This is an ongoing single-arm, multi-center, open-label real-world study conducted in China. The study would enroll 200 pts with unresectable or surgical resection with positive margins BTC. Pts would receive surufatinib with or without combination as adjuvant (namely pts with positive margin after resection), first- or further-line therapy, at a proper dose (200-300mg) judged by physicians once per day in 28-day cycles. The primary endpoint is relapse-free survival (RFS) for pts whose primary lesions were resected, and progression-free survival (PFS) for those had evaluable lesions. If available, tumor assessments were performed every 2 cycles ± 7 days according to RECIST version 1.1. Results: By Sep 10, 2023, 56 eligible pts had been enrolled, of whom 16 (28.6%) were female. The median age was 64 (range: 39-81). 28 (50.0%), 24 (42.9%), and 4 (7.1%) pts received surufatinib as adjuvant, first-line, and above treatment, respectively. As to location, 23 cases were intrahepatic cholangiocarcinoma (ICC), and 33 cases were extrahepatic cholangiocarcinoma (ECC) or gallbladder cancer (GBC). With a median follow-up time of 9.5 (range: 1.1-20.3) mo, the global mRFS/mPFS was 10.4 (95% CI: 9.0-13.9) mo. The mRFS of pts who received surufatinib as adjuvant treatment was 11.3 (95% CI: 10.4-NA) mo, and mPFS of those who received surufatinib as systematic treatment was 9.0 (95% CI: 7.8-10.8) mo. Pts with ICC demonstrated an mRFS/mPFS of 10.4 (5.8-NA) mo, and those with ECC or GBC demonstrated 10.4 (9.5-NA) mo. The global mOS was 15.8 (12.4-NA) mo. Among those with primary lesion unresected (n=28), 2 pts (7.1%) achieved CR, 5 (17.9%) pts PR, 16 (57.1%) pts SD, and 5 (17.9%) pts suffered PD. The ORR was 25.0%, and DCR was 82.1%. No new safety signal was observed. Conclusions: Surufatinib exhibited promising efficacy and manageable toxicity on pts with BTC in the real-world setting. Clinical trial information: NCT05064852 .
SKYSCRAPER-08: A phase III, randomized, double-blind, placebo-controlled study of first-line (1L) tiragolumab (tira) + atezolizumab (atezo) and chemotherapy (CT) in patients (pts) with esophageal squamous cell carcinoma (ESCC).
Authors: Chih-Hung Hsu, Zhihao Lu, Shegan Gao, Jun-Ye Wang, Jong-Mu Sun, Tianshu Liu, Qingxia Fan, Jun Cai, Feijiao Ge, Sijing Li, Li Zhang, Edward Cha, Lin Shen
Journal: Journal of Clinical Oncology (2024)

245 Background: Inhibition of TIGIT, a novel checkpoint inhibitor, may further amplify immune responses by complementing the PD-L1/PD-1 pathway. Anti-tumor activity has been demonstrated with cancer immunotherapy in ESCC. SKYSCRAPER-08 (NCT04540211) is evaluating the efficacy and safety of tira (anti-TIGIT) + atezo (anti-PD-L1) in combination with CT compared with placebo + CT as 1L treatment (tx) in an Asian population with unresectable locally advanced (LA), unresectable recurrent, or metastatic (R/M) ESCC. Methods: Eligible pts (confirmed LA or R/M ESCC; ECOG PS 0–1; no prior systemic tx) were randomized 1:1 to receive tira 600mg + atezo 1200mg + CT (paclitaxel 175mg/m2 + cisplatin 60–80mg/m2, local standard of care) or placebo + CT on Day 1 of each 21-day cycle (cycles 1–6); followed by tira + atezo or placebo maintenance until loss of clinical benefit/unacceptable toxicity. Primary endpoints: independent review facility (IRF)-assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints: investigator (INV)-assessed PFS, objective response rate (ORR), duration of response (DoR), and safety. Results: Overall, 461 pts were randomized (tira + atezo + CT, n= 229; placebo + CT, n=232). Pt characteristics were generally balanced between arms. As of 15 June 2022 (minimum survival follow-up 6.5 months [mo]; PFS primary analysis), median IRF-assessed PFS was 6.2 mo for tira + atezo + CT vs 5.4 mo for placebo + CT (HR 0.56; 95% CI: 0.45, 0.70; P&lt;0.0001). As of 13 Feb 2023 (minimum survival follow-up 14.5 mo; OS final analysis), median OS was 15.7 mo for tira + atezo + CT vs 11.1 mo for placebo + CT (HR: 0.70; 95% CI: 0.55, 0.88; P= 0.0024). INV-assessed PFS, IRF-assessed ORR and DoR are presented in Table. Treatment-related adverse events (TRAEs) occurred in 98.2% of pts (both arms); Grade 3/4 TRAEs in 59.6% (tira + atezo + CT) and 56.4% (placebo + CT) of pts; Grade 5 TRAEs in 2.6% (tira + atezo + CT) and 0.9% (placebo + CT) of pts. Conclusions: The study met both primary endpoints of IRF-assessed PFS and OS, demonstrating statistically significant and clinically meaningful improvements in PFS and OS for tira + atezo + CT over placebo + CT. Generally consistent benefit was observed across subgroups, including PD-L1 status. The safety profile was consistent with the known risks of the individual tx. Clinical trial information: NCT04540211 . [Table: see text]