Dataset Information

Effectiveness and Safety of Toripalimab Combination Therapies for Patients With Chemo-Resistant Choriocarcinoma.

ABSTRACT: Toripalimab as a novel PD-1 inhibitor has presented its promising efficacy in patients who developed chemo-refractory carcinomas, whereas no study has ever investigated the effectiveness of toripalimab in chemo-resistant choriocarcinoma. Here we reported the effectiveness and safety data of 4 patients with chemo-resistant choriocarcinoma who underwent PD-1 antibody therapy by toripalimab and individualized chemotherapies. From January 2019 to August 2020, 4 patients with choriocarcinoma were admitted in Shengjing Hospital of China Medical University. The patients' age ranged from 29 to 52 years with a median of 36 years. All the patients achieved CR after the combined therapy of toripalimab with individualized chemotherapies according to the decreased serum β-hcg level. Two of the four patients were observed with treatment-related adverse events (AEs), including one grade I skin rash and one grade I pruritus. Our cases showed that toripalimab combined with chemotherapy presented a tolerable safety profile and promising effectiveness in patients with chemo-resistant choriocarcinoma, indicating its potential as salvage therapy for this subset of patients.

SUBMITTER: Liu X

PROVIDER: S-EPMC9047865 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Effectiveness and Safety of Toripalimab Combination Therapies for Patients With Chemo-Resistant Choriocarcinoma.

Liu Xiaomei X Li Xiuqin X Qu Hui H Zhang Shiyue S Zhang Ruizhe R Du Zhenhua Z

Frontiers in oncology 20220414

Toripalimab as a novel PD-1 inhibitor has presented its promising efficacy in patients who developed chemo-refractory carcinomas, whereas no study has ever investigated the effectiveness of toripalimab in chemo-resistant choriocarcinoma. Here we reported the effectiveness and safety data of 4 patients with chemo-resistant choriocarcinoma who underwent PD-1 antibody therapy by toripalimab and individualized chemotherapies. From January 2019 to August 2020, 4 patients with choriocarcinoma were adm ...[more]

PMID: 35494052

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Project description:Prostate cancer remains a significant public health concern in sub-Saharan Africa, particularly impacting South Africa with high mortality rates. Despite many years of extensive research and significant financial expenditure, there has yet to be a definitive solution to prostate cancer. It is not just individuals who vary in their response to treatment, but even different nodules within the same tumor exhibit unique transcriptome patterns. These distinctions extend beyond mere differences in gene expression levels to encompass the control and networking of individual genes. Escalating chemotherapy resistance in prostate cancer patients has prompted increased research into its underlying mechanisms. The heterogeneous nature of transcriptomic organization among men makes the pursuit of universal biomarkers and one-size-fits-all treatments impractical. This study delves into the expression of drug resistance-associated genes, ABCB1 and CYP1B1, in cancer cells. Employing bioinformatics, we explored the molecular pathways and cascades linked to drug resistance following upregulation of these genes. Samples were obtained from archived prostate cancer patient specimens through pre-treatment biopsies of two categories: good vs. poor responders, with cDNAs synthesized from isolated RNAs subjected to qPCR analysis. The results revealed increased ABCB1 and CYP1B1 expression in tumor samples of the poor responders. Gene enrichment and network analysis associated ABCB1 with ABC transporters and LncRNA-mediated therapeutic resistance (WP3672), while CYP1B1 was linked to ovarian steroidogenesis, tryptophan metabolism, steroid hormone biosynthesis, benzo(a)pyrene metabolism, the sulindac metabolic pathway, and the estrogen receptor pathway, which are associated with drug resistance. Both ABCB1 and CYP1B1 correlated with microRNAs in cancer and the Nuclear Receptors Meta-Pathway. STRING analysis predicted protein-protein interactions of ABCB1 and CYP1B1 with Glutathione S-transferase Pi, Catechol O-methyltransferase, UDP-glucuronosyltransferase 1-6, Leucine-rich Transmembrane and O-methyltransferase (LRTOMT), and Epoxide hydrolase 1, with scores of 0.973, 0.971, 0.966, 0.966, and 0.966, respectively. Furthermore, molecular docking analysis of the chemotherapy drug, docetaxel, with CYP1B1 and ABCB1 revealed robust molecular interactions, with binding energies of -20.37 and -15.25 Kcal/mol, respectively. These findings underscore the susceptibility of cancer patients to drug resistance due to increased ABCB1 and CYP1B1 expression in tumor samples from patients in the poor-responders category that affects associated molecular pathways. The potent molecular interactions of ABCB1 and CYP1B1 with docetaxel further emphasize the potential basis for chemotherapy resistance.

Project description:IntroductionThis was the first phase 1 study conducted in the United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion (part B), investigating the safety and preliminary efficacy of toripalimab (anti-programmed cell death-1 inhibitor) in patients with advanced malignancies.MethodsPatients with advanced malignancies that progressed after treatment with at least one prior line of standard systemic therapy, including the patients with advanced/recurrent cholangiocarcinoma (CCA), received toripalimab 240 mg every 3 weeks in part B. The primary endpoint was safety assessment. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) as assessed by the investigators according to Response Evaluation Criteria in Solid Tumors (version 1.1) and overall survival (OS).ResultsIn part B, 166 patients, including the 42 patients with CCA, were enrolled and received toripalimab. Among the 166 patients, treatment-emergent adverse events (TEAEs) of any grade occurred in 158 (95.2%) patients, and 97 (58.4%) patients experienced TEAEs of Grade 3 or greater. The most common TEAE was fatigue (42.2%). Seven (4.2%) patients experienced TEAEs with a fatal outcome, none of which were identified by investigators as related to toripalimab. Investigator-assessed immune-related adverse events (irAE) of Grade 3 or higher occurred in 7 (4.2%) patients. In the CCA cohort, with the median follow-up of 4.4 months, the ORR and DCR were 4.8% (95% CI: 0.58, 16.16) and 40.5% (95% CI: 25.63, 56.72), respectively; median DoR was 7.8 (range 4.4+ to 7.8) months; median PFS was 2.1 (95% CI: 1.91, 3.88) months; median OS was not estimable.ConclusionsToripalimab had manageable side effects in patients with refractory cholangiocarcinoma and exhibited preliminary evidence of anti-tumor activity. However, further information regarding biomarkers is needed. ClinicalTrials.gov ID: NCT03474640.

Dataset Information

Effectiveness and Safety of Toripalimab Combination Therapies for Patients With Chemo-Resistant Choriocarcinoma.

Publications

Effectiveness and Safety of Toripalimab Combination Therapies for Patients With Chemo-Resistant Choriocarcinoma.

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