tbuckley/cabot-search huggingface dataset:
The feasibility and tolerability of anlotinib plus PD-1 blockades among patients with previously immunotherapy treated advanced esophageal squamous cell carcinoma (ESCC): Update results of a retrospective exploratory study.
Authors: Jing Huang, Yong-Gui Hong, Jun Liu, Ping Lu, Zhiwei Chang, Guifang Zhang, Xiumei Ma, Wei Liang, Yongjing Tian, Jin Xia, Heng Cao
Journal: Journal of Clinical Oncology (2024)

e16006 Background: Immunotherapy (ICI) demonstrated promising efficacy for patients with advanced ESCC in both second-line and first-line treatment clinically. Therefore, whether the patients might benefit from the PD-1 blockades-related regimens when they failed after the previous ICI remained to be identified and the feasibility of PD-1 blockades rechallenge in ESCC was warranted to be explored. As a novel oral multi-targeted tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferation, anlotinib was an efficacious second-line monotherapy for ESCC in China and the combination of anlotinib plus PD-1 blockades might be a promising strategy for patients with previously ICI treated advanced ESCC. Methods: This multicenter, retrospective study was planned to include 110 patients with previously ICI treated advanced ESCC from 9 hospitals in China who were treated with anlotinib plus PD-1 blockades in clinical practice from July 2018 to November 2022 consecutively. The Outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Results: At the date of data-cutoff (May 12 2023), 110 eligible patients were available to be analyzed. Characteristics were as follows: median age of 64 years, male/female 74.5%/25.5%, ECOG PS 0/1/2 22.7%/75.5%/1.8%, clinical stage II/III/IV 0.9%/20.9%/78.2%. All the patients had received ICIs and 10.9% patients were treated with TKIs previously. 39.1% patients had received first-line therapy, 41.8% patients had received second-line, 19.1% patients had received third or above line previously. Prognostic outcomes exhibited that the median OS was 11.1 months (95%CI: 8.6-13.7), 12-month OS rate, 24-month OS rate were 47.6% and 30.8%, separately. Additionally, the median PFS was 5.6 months (95%CI: 4.4-6.8). In 110 patients, ORR was 19.1% (95%CI: 12.2%-27.7%), DCR 69.1% (95%CI: 59.6%-77.6%). Safety profile of anlotinib plus PD-1 blockades indicated that the treatment related adverse events (TRAEs) were 89.1%. The most common TRAEs were anaemia (62.7%), hypothyroidism (25.5%), hypoalbuminemia (21.8%), lymphocytopenia (20%), leukopenia (19.1%). Conclusions: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and tolerable adverse reactions among patients with advanced ESCC who had received immunotherapy previously and the feasibility of PD-1 blockades rechallenge in ESCC was promising to be elucidated. Clinical trial information: ChiCTR2300070777.
An open-label, placebo-controlled, randomized phase II trial of camrelizumab combined with or without apatinib or capecitabine in the treatment of previously treated advanced pancreatic cancer.
Authors: Jianhua Chen, Jun Liu, Ning Li, Weiyi Huang, Donghui Chen, Wei Tao, Hongxia Wang
Journal: Journal of Clinical Oncology (2024)

e16324 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancer types that have essentially no clinical benefit from immune checkpoint inhibitors therapy, combined immunotherapy is expected to solve this dilemma. We conducted a randomized open-label, placebo-controlled phase II trial evaluating the efficacy of camrelizumab combined with apatinib or capecitabine in the treatment of patients with previously treated metastatic PDAC (ChiCTR1900024095). Methods: Eligible patients (n = 30) were randomized 1:1:1 to receive camrelizumab (200 mg q2w) combined with apatinib (250mg qd, d1-28, q4w) or capecitabine (1000 mg/m2, bid d1-14, q3w), or placebo plus capecitabine (1000 mg/m2, bid d1-14, q3w) until disease progression or unacceptable toxicity. Tumor response was assessed every 8 weeks according to RECISTv1.1. Primary endpoints were investigator-assessed 6-month overall survival (OS) rate. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Data cutoff date for the prespecified interim OS and final PFS analysis was Oct 30, 2022. Results: In the primary endpoint analysis, camrelizumab combined treatment showed improved 6-month OS rates, whether in the camrelizumab-apatinib arm (83.3% versus 33.3%, p = 0.1189) or in the camrelizumab-capecitabine arm (100% versus 33.3%, p = 0.0098), compared placebo-capecitabine, respectively. Median PFS was 5.4 months, HR 0.58, [95% confidence interval (CI), 0.21–1.59] in the camrelizumab-apatinib arm , 3.1 months HR 0.98, [95%CI, 0.35–2.77] in the camrelizumab-capecitabine arm , and 2.6 months in the placebo-capecitabine, respectively. The ORR and DCR were 0% and 66.7% in the camrelizumab-apatinib arm, 40% and 50% in the camrelizumab-capecitabine arm, 0% and 44.4% in the placebo-capecitabine, respectively. PR was observed in two patients receiving camrelizumab-capecitabine treatment. The median DoR were 5.3 months in the camrelizumab-apatinib arm, 4.3 months in the camrelizumab-capecitabine arm, and 2.1 months in the placebo-capecitabine arm. Treatment-related adverse event rates were slightly increased in camrelizumab combined arms. Incidences of grade ≥3 treatment-related adverse events were comparable between the three groups (20%、 10% vs 0%), with reactive cutaneous capillary endothelial proliferation (10%) as the most common one in Camrelizumab combinations. Conclusions: Camrelizumab combined treatment showed improved 6-month OS vs conventional capecitabine monotherapy, with a manageable safety profile. These analyses revealed combined immunotherapy could be used as a new option for posterior line treatment in previously treated metastatic PDAC. Clinical trial information: ChiCTR1900024095.
TisCRT-LAPC: A phase II study of tislelizumab combined with nab-paclitaxel and gemcitabine (AG) followed by consolidative radiotherapy in locally advanced pancreatic cancer (LAPC).
Authors: Xi Guo, Yuhong Zhou, Yuan Ji, Wenhui Lou, Lili Wu, Wenquan Wang
Journal: Journal of Clinical Oncology (2024)

e16350 Background: We have previously reported that consolidative chemoradiotherapy following induced chemotherapy is an optimal regimen for LAPC. This study aimed to evaluate the clinical benefit of tislelizumab (anti-PD-1) plus AG chemotherapy sequenced by consolidative radiotherapy for therapy-naive LAPC. Methods: Patients (pts) with LAPC were enrolled and received tislelizumab (TIS) 200mg Q3W, nab-paclitaxel 125 mg/m 2 and gemcitabine 1,000 mg/m 2 on days 1 and 8 every three weeks for 6 cycles. Those who did not progressed continued to receive radiotherapy and tislelizumab. After that, tislelizumab and gemcitabine were ongoing until progression. The primary endpoint was 12-month progression-free survival rate, and secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety and biomarker explore. Results: From April 2021 to December 2023, 30 pts were enrolled, 29 pts completed at least one efficacy assessment, 1 dropped out due to jaundice on liver damage for more than 6 weeks without medication. 17 males and 13 females with a median age of 58.5 years. 12.5% (3/24) progressed after TIS+AG treatment and did not receive radiotherapy, 87.5% (21/24) had completed radiotherapy and 5 pts were still receiving TIS+AG treatment. ORR was 31.0%, and DCR was 96.6%, respectively. The median follow-up time was 14.0 months, and the median PFS was 11.2 months (95%CI,7.6-26.6). The median OS was not reached. 6-month and 12-month PFS rates were 84.2% and 44.3%, respectively. Most patients (27/30) showed serum CA19-9 decline with different degrees.The most common treatment-emergent adverse events (TEAEs) were myelosuppression, rash, and fatigue. Grade 3/4 TEAEs were neutropenia in 5 patients, anemia in 1 patient, and rash in 1 patient. Immune-related AEs included 1 Grade-1 myocarditis, 1 Grade-1 pneumonia and 1 Grade-3 disfunction of liver. Conclusions: This study demonstrates the effectiveness and manageable safety of tislelizumab combined with AG chemotherapy sequenced by radiotherapy for LAPC. Exploratory analysis of correlative biomarkers suggests that KRAS ctDNA negative at baseline may be a pedictive markers benefit with treatments. Clinical trial information: ChiCTR2000040872.
A prospective phase II study of an exercise-nutrition-psychology integrated rehabilitation model based on mobile health and virtual reality for patients with cancer.
Authors: Yuan Qi, Ya Xue, MengJie Wang, Jingyan Yue, Weifen Meng, Wenyu Zhu, Xiaolin Pu, Dongqing Li, Hua Jiang
Journal: Journal of Clinical Oncology (2024)

e13786 Background: The optimal rehabilitation model for patients with cancer is unclear. Nutritional and psychological interventions have proven to be beneficial for this population. Although mobile health (mHealth) and virtual reality (VR) advances have transformed many clinical areas including cardiovascular and psychiatric care, they are relatively nascent in cancer care. Due to the multidimensional rehabilitation needs of patients, here we explored the feasibility of an exercise-nutrition-psychology rehabilitation model in cancer patients, which based on VR and mHealth. Methods: A single-center, single-arm, prospective phase II study was conducted from November 2022 to April 2023. With the help of mHealth participants received standard cancer therapy and integrated interventions featuring in-person group-based exercise classes, at-home physical activity prescription, behavior change education, nutritional instruction, oral nutritional supplements (Ainst, China), music therapy (MT), VR treatment and psychological counselling. The rehabilitation was provided by a team of medical oncologists, dietitians, psychotherapists, and technicians. An effective intervention course includes two consecutive hospitalization and two periods of home-based rehabilitation (total 8 weeks). The primary endpoint was the feasibility. The paired T test was used to analyze and compare the differences. Results: At the cutoff date of April,10, 2023. 165 patients were screened, 123 were recruited, and the recruitment rate was 75% (123/165). 14 (11.4%) patients were lost to follow-up, and 4 (3.25%) withdrew halfway. Respectively, the completion rate of exercise, nutrition, and VR and mHealth based psychology were 55% (68 / 123), 85% (105 / 123), and 63% (78 / 123). The parameters in nutrition, psychology, and muscle mass after the rehabilitation showed significant improvements than before (P&lt;0.05). There was no significant statistical difference (P&gt; 0.05)in 6-minute walking speed and handgrip strength. All functional domains of life quality were significantly improved, except role optimization function (P&gt; 0.05). Conclusions: The mHealth and VR based exercise-nutrition-psychology integrated rehabilitation model is feasible for cancer patients and shows potential benefits. The mHealth application (app) we used is a rudimentary version and needs to be optimized in the future. This rehabilitation model warrants further investigation in a larger cohort trial. Clinical trial information: ChiCTR2200065748.
Efficacy and safety analysis of donafenib combined with transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: A prospective, single-arm, single center, phase II clinical study.
Authors: Jinpeng Li, Hua Chen, Jinlong Song
Journal: Journal of Clinical Oncology (2024)

e16134 Background: To observe and assess the efficacy of donafenib combined with TACE in the treatment of unresectable hepatocellular carcinoma. Methods: It was a prospective, single-arm, single center, and phase II clinical study. A total of 34 initial unresectable HCC patients who had not received any systemic treatment were enrolled. The patients received donafenib ( 100mg po bid), TACE and or not and camrelizumab (200mg iv Q3W). The primary endpoint was short-term efficacy based on mRECIST criteria, with secondary endpoints including PFS, TTR, DCR and adverse events (AEs).The diameter of tumor feeding artery was measured. Results: A total of 36 patients were included in the study, including 26 who received donafenib and TACE and 10 who received donafenib and TACE plus PD-1 inhibitors. A total of 34 subjects were eligible for efficacy evaluation, and among them, there were 4 cases of CR, 17 cases of PR, 10 cases of SD and 3 cases of PD; Four patients (11.8%) successfully underwent conversion therapy and all achieved R0 resection. Two patients achieved a complete pathological response. The ORR was 61.8% and the DCR was 91.2% based on mRECIST criteria. The mPFS was 10.7 months (95%CI: 8.37-NA months), median OS was not reached, median TTR was 1.4 months ( 95% CI: 0.8-6.9 months). The 6 moths and 12 moths progression-free survival rate were 73.4% and 47.9% respectively. Treatment related adverse events (TRAEs) occurred in all 25 subjects, and grade 3 TRAE occurred in 4 subjects (11.3%), and no grade 4 or 5 TRAE occurred. The tumor feeding artery diameter was (4.5±1.4)mm pre-treatment, and reduced to (3.2±1.1)mm post-treatment (P = 0.036). The multivariable analysis indicated that the sum of baseline target lesion diameters、best tumor response and post-treatment tumor artery diameter were independent predictor for PFS. Conclusions: TACE combined with donafenib could reduce the tumor feeding artery diameter, which had a good safety profile and a high objective response rate in patients with unresectable HCC. Clinical trial information: ChiCTR2100054041.
Safety and efficacy of camrelizumab and apatinib in combination with IMRT in unresectable hepatocellular carcinoma: A non-randomised phase 2 study.
Authors: Wei-Hu Wang, Baocai Xing, Hongzhi Wang, Xianggao Zhu, Kun Wang, Xuan Zheng, Dezuo Dong
Journal: Journal of Clinical Oncology (2024)

e16157 Background: This study aimed to assess the efficacy and safety of combining Camrelizumab (an anti-programmed death 1 antibody) and Apatinib (a tyrosine kinase inhibitor) with intensity-modulated radiotherapy (IMRT) in patients with unresectable hepatocellular carcinoma (HCC). Methods: This non-randomized phase 2 study enrolled patients with unresectable HCC who were either systemic treatment-naïve or refractory/intolerant to first-line targeted therapy. The enrolled patients received IMRT at a dose of 50-60 Gy in 25-30 fractions, with the target volume encompassing all visible lesions. Patients were administered Camrelizumab intravenously at a dose of 200 mg every 3 weeks and Apatinib orally a dose of 250 mg once daily during IMRT, continuing for 2 years or until unacceptable toxicity or disease progression. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), local control (LC) rate, overall survival (OS) and adverse events. Results: From October 2020 to January 2024, 33 patients were included in the preliminary analysis (31 men and 2 women; median age, 57 years [range, 39-77 years]). Among them, 30 patients were diagnosed with BCLC stage C (90.9%). The median number of lesions was one (range, 1-5), with a median tumor diameter of 6.0 cm (range, 2.6-16.0 cm). Tumor thrombus was observed in 22 cases (66.7%), and lymph node metastases was found in 6 cases (18.2%). The ORR based on RECIST 1.1 and modified RECIST criteria were 78.8% and 90.9%, respectively, with a complete response (CR) rate of 12.1% and 54.5%, respectively. The median follow-up time was 20.0 months (range, 3.3-38.6 months). The LC rate at 2 years was 88.3% (95% CI, 68.1-96.1%). The median PFS was 17.5 months (95% CI, 12.6-NA), and the PFS rate at 2 years was 43.9% (95% CI, 26.1-73.8%). The median OS was 25.9 months (95% CI, 14.0-NA), and OS rate at 2 years was 58.5% (95% CI, 41.9-81.6%). According to CTCAE 5.0, grade 3-4 treatment-related adverse events were observed in 27 patients (81.8%), with the most common being thrombocytopenia (42.5%), leukopenia (33.3%) and hypertension (39.4%). No treatment-related deaths occurred. Conclusions: The combination of systematic therapies involving Camrelizumab and Apatinib with local-regional treatment of IMRT showed promising outcomes and manageable toxicities in patients with unresectable HCC. These findings warrant to be confirmed in phase 3 prospective studies. Clinical trial information: ChiCTR2000035052.
A single-arm, prospective study on the efficacy and safety of TACE-HAIC combined with lenvatinib and tislelizumab in the treatment of unresectable hepatocellular carcinoma.
Authors: Jun Zhu, Xu Feng, Jintao Duan, Yu Fu, Jie Liang, Mi Peng, Zimo Zhu
Journal: Journal of Clinical Oncology (2024)

e16143 Background: Hepatocellular carcinoma is one of the common tumors in China. In recent years, innovative drugs such as molecular targeted drugs and immune preparations have begun to be used clinically and have achieved good results. Interventional therapy combined with targeted immunotherapy has become a hot topic in HCC treatment research. However, the matching mode, application timing, efficacy and safety of various combination treatment options are still unclear. Therefore, a study of TACE-HAIC combined with lenvatinib and tislelizumab in the treatment of unresectable hepatocellular carcinoma is conducted to evaluate the efficacy and safety. Methods: According to the inclusion and exclusion criteria, 15 patients with unresectable hepatocellular carcinoma were included, all of whom received TACE-HAIC combined with lenvatinib and tislelizumab. The mRECIST criteria is used to evaluate the objective response rate (ORR) and disease control rate (DCR).The CTCAE version 5.0 is used to grade treatment-related adverse events of TACE-HAIC combined with lenvatinib and tislelizumab. Results: Among the 15 patients included in the study, 14 are male and 1 is female. All patients were treated with TACE-HAIC combined with lenvatinib and tislelizumab as planned, and the treatment was well tolerated. The total number of patients for optimal efficacy evaluation is 15, including 5 patients with CR, 8 patients with PR, and 2 patients with SD. The ORR is 86.7%, and DCR is 100% in best efficacy. In the safety analysis set (n = 15), none TEAEs is ≥ grade 3. In the treatment-related adverse events, abdominal pain(8/15, 53.3%), fever(4/15, 26.7%), vomiting(4/15, 26.7%), weight loss(4/15, 26.7%), nausea(2/15, 13.3%), neutropenia(2/15, 13.3%) and liver function damage(1/15, 6.7%) are all ≤ grade 2. Conclusions: TACE-HAIC combined with lenvatinib and tislelizumab has definite efficacy in the treatment of patients with unresectable hepatocellular carcinoma, with high objective response rate, good treatment tolerance, and controllable treatment-related adverse events. This therapy may be a treatment option for patients with unresectable hepatocellular carcinoma. Clinical trial information: ChiCTR2300067362. [Table: see text]
Real-world data of a regimen containing zimberelimab in the treatment of recurrent and metastatic cervical cancer.
Authors: Qiuhong Tian, Qin Xu, Fan Li, Jin Huang, Jing Liu, Lele Zang, Li Ting, Lianxiang He, Wenhan Yang
Journal: Journal of Clinical Oncology (2024)

e17521 Background: Cervical cancer is the malignant tumor in women. Zimberelimab is approved by NMPA for PD-L1 positive recurrent and metastatic cervical cancer. However, no real-world data of zimberelimab in recurrent and metastatic cervical cancer have been reported before. Methods: From August 2021 to March 2023, we retrospectively collected patient data at the First Affiliated Hospital of Nanchang University and Fujian Cancer Hospital. Patients with advanced or recurrent cervical cancer who had been pathologically diagnosed were eligible, regardless of whether they had squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma and PD-L1 status. All patients were treated with regimen containing zimberelimab. Date of brith, previous medical history, tumor stage at first diagnosis, metastatic sites, pathological type, HPV infection and PD-L1 expression status, and treatment regimen containing zimberelimab will be recorded. The primary endpoint was objective response rate and disease control rate assessed by RECIST1.1. The study has been approved by the First Affiliated Hospital of Nanchang University Ethics (No 317). (ChiCTR2300078205). Results: A total of 34 patients were eligible for evaluations of efficacy. 21 from the First Affiliated Hospital of Nanchang University and 13 from the Fujian Cancer Hospital. The median age was 53.23 years (range, 37–66). The ECOG PS was 1 for 23 cases (67.65%), 2 for 10 cases (29.41%).3 for 1 case (2.94%). Squamous cell carcinoma (28,82.35%) was the most common pathological subtype, and the most metastatic site were lymph node (26,76.47%), lung (10,29.41%), bone (6,17.65%), liver (1,2.94%), vulva (1,2.94%), peritoneal (1,2.94%) and bladder (1,2.94%). 32(94.12%) and 30(88.24%) patients have not test for PD-L1 statue or HPV infection. The best overall response of each patient was recorded to evaluate the efficacy. The objective response rate (ORR) in 34 patients were 52.94%, and the disease control rate (DCR) were 97.06%. And 25 patients had previously had ≥1 chemotherapy, and they was treated with a zimberelimab-based combination regimen. The ORR and DCR for these individuals were 52% and 96%, respectively. Conclusions: This is the first report of real-world data on zimberelimab, and zimberelimab combination therapy demonstrated quite good efficacy in patients with recurrence and metastatic cervical cancer who had previously received chemotherapy. Clinical trial information: ChiCTR2300078205. [Table: see text]