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Purpose: This research intends to investigate the treatment of non-small cell lung cancer (NSCLC) using Toripalimab, focusing on its effectiveness and safety profile. Efficacy refers to the survival prognosis, while safety pertains to the occurrence of adverse events in our study. It also aims to provide reference information for neoadjuvant and postoperative therapies. Methods: Up to March 20, 2024, studies on randomized controlled trials and single-arm trials involving Toripalimab for NSCLC were sourced from the Cochrane Library, Embase, PubMed, and Web of Science databases. Data extraction and analysis were independently conducted by two researchers utilizing Stata 15.0 and R software. Results: A total of 8 studies were analyzed, including 6 single-arm studies and 2 randomized controlled trials (RCTs). Toripalimab treatment in the RCTs showed an overall survival (OS) of [HR=0.67, 95% CI (0.53, 0.85); p=0.71]. The objective response rate (ORR) from single-arm studies was reported as [ES=0.59, 95% CI (0.36, 0.81); p<0.01], and progression-free survival (PFS) was [ES=4.89, 95% CI (2.65, 9.02); p<0.01]. Furthermore, observed adverse effects included Anemia [OR=0.53, 95% CI (0.26, 0.79); p<0.01], Neutropenia [OR=0.43, 95% CI (0.20, 0.68); p<0.01], and Thrombocytopenia [OR=0.28, 95% CI (0.18, 0.43); p<0.01]. Conclusions: Toripalimab, being China's first domestically developed anti-tumor PD-1 antibody drug, shows potential advantages over traditional chemotherapy in possibly prolonging patients' survival times. However, the limited number of studies included indicates the need for additional single-arm and RCT studies to further validate these findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier (CRD42024519806). [ABSTRACT FROM AUTHOR]

Background: Sarcomatoid urothelial carcinoma (SUC) is a rare renal malignancy. Its biological malignancy is high, the prognosis is poor, diagnostic and treatment options are few, and there is no standard treatment plan. Case presentation: In this case, a 64-year-old woman was hospitalized with fever and lower back pain one week previously. The preliminary diagnosis was a right kidney stone with a urinary tract infection. After the anti-infection treatment, a percutaneous right nephrostomy was performed. The intraoperative biopsy (renal pelvis) finding was infiltrating urothelial carcinoma with a sarcomatoid variation. Subsequently, radical surgery was performed for cancer of the right renal pelvis. Implant metastasis of the abdominal wall and adjacent abdominal cavity occurred half a month after the surgery. The lesion was resected again, and two cycles of doxorubicin plus carboplatin chemotherapy were administered. However, the disease progressed more rapidly after the chemotherapy. With the written consent of the patient, the treatment was altered to targeted immune therapy with toripalimab plus anlotinib. A clinical cure was achieved after nine cycles of treatment with no obvious lesions on imaging. The maintenance therapy was administered consecutively for over a year, and the patient is at present still in good condition with a disease-free survival exceeding two years. Conclusion: This case proves that the combination of toripalimab and anlotinib is effective in the treatment of recurrent renal SUC. To the best of our knowledge, this is the first reported case of a patient with advanced recurrent urothelial carcinoma of the renal pelvis sarcomatoid cured with this therapy. [ABSTRACT FROM AUTHOR]

Background: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib showed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumors in a phase I study. Methods: This open-label, multi-cohort study in China enrolled patients with advanced solid tumors who had failed or were intolerable to standard treatment into tumor-specific cohorts. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every three weeks). Results for three cohorts (gastric/gastroesophageal junction [GC/GEJ] adenocarcinoma, esophageal squamous cell carcinoma [ESCC], and biliary tract carcinoma [BTC]) are reported here. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation criteria in Solid Tumors version 1.1. Results: Between December 17, 2019, and January 29, 2021, 60 patients were enrolled (GC/GEJ, n = 20; ESCC, n = 20; BTC, n = 20). At data cutoff (February 28, 2023), ORRs were 31.6%, 30.0%, and 11.1%, respectively. Median progression-free survival was 4.1, 2.7, and 2.9 months, respectively. Median overall survival was 13.7, 10.4, and 7.0 months, respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 28 (46.7%) patients. Conclusions: Surufatinib plus toripalimab showed promising antitumor activity and a tolerable safety profile in immunotherapy-naïve patients with GC/GEJ adenocarcinoma, ESCC, or BTC. These findings warrant further study in larger randomized trials comparing surufatinib plus toripalimab with standard therapies in these tumors. ClinicalTrials.gov NCT04169672. [ABSTRACT FROM AUTHOR]

PurposeThis research intends to investigate the treatment of non-small cell lung cancer (NSCLC) using Toripalimab, focusing on its effectiveness and safety profile. Efficacy refers to the survival prognosis, while safety pertains to the occurrence of adverse events in our study. It also aims to provide reference information for neoadjuvant and postoperative therapies.MethodsUp to March 20, 2024, studies on randomized controlled trials and single-arm trials involving Toripalimab for NSCLC were sourced from the Cochrane Library, Embase, PubMed, and Web of Science databases. Data extraction and analysis were independently conducted by two researchers utilizing Stata 15.0 and R software.ResultsA total of 8 studies were analyzed, including 6 single-arm studies and 2 randomized controlled trials (RCTs). Toripalimab treatment in the RCTs showed an overall survival (OS) of [HR=0.67, 95% CI (0.53, 0.85); p=0.71]. The objective response rate (ORR) from single-arm studies was reported as [ES=0.59, 95% CI (0.36, 0.81); p

Background To investigate the efficacy and toxicity after long-term follow-up of anti-PD-1 antibody in advanced melanoma with predominantly acral and mucosal subtypes. Methods and Patients In the POLARIS-01 phase II trial, 128 Chinese patients with advanced melanoma refractory to standard therapy received toripalimab until disease progression or unacceptable toxicity for ≤2 years. For those who progressed after discontinuation due to 2-year treatment completion, rechallenge was allowed. The primary objectives were safety and overall response rate (ORR). Results As of February 8, 2021, ORR was 17.3% (95% CI: 11.2-25.0) evaluated by the independent radiologic review committee. The median overall survival (OS) for patients with known melanoma subtypes was 16.3 m for acral, 41.5 m for nonacral cutaneous, and 10.3 m for mucosal melanoma. Thereafter, the evaluation was continued by investigators. As of November 4, 2022, 5 years after the last enrollment, median duration of response was 15.6 months (range, 3.7-64.5+), median progression-free survival (PFS) was 3.5 months (95% CI, 2.2-5.3), and 60-month OS rate was 28.5% (95% CI: 20.2-37.2). Thirteen patients completed a 2-year treatment of toripalimab, with the subtypes of acral (2/13), non-acral cutaneous (4/13), mucosal (3/13) and unknown primary (4/13). Five patients were rechallenged. Four of them, all of whom were non-mucosal, completed the rechallenge course of 2 years with PFS ≥ 24 months. Conclusions This is the largest prospective anti-PD-1 trial with mature data in advanced melanoma in China. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma who had failed in standard therapy. Immunotherapy seems less efficacious for long-term responders with mucosal primaries as rechallenge therapy. [ABSTRACT FROM AUTHOR]

The current analysis aimed to evaluate the economic benefit of toripalimab plus axitinib for previously untreated RCC patients from the Chinese healthcare system perspective. The partitioned survival model was developed to simulate 3-week patients' transition in 20-year time horizon to evaluate the cost-effectiveness of toripalimab plus axitinib compared with sunitinib for advanced RCC. Survival data were gathered from the RENOTORCH trial, and cost and utility inputs were obtained from the database and published literature. Total cost, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were the model outputs. Subgroup analyses and sensitivity analyses were conducted to increase the comprehensiveness and estimate the robustness of the model results. In the base-case analysis, compared with sunitinib, toripalimab plus axitinib could bring additional 1.19 LYs and 0.65 QALYs, with the marginal cost of $41,499.23, resulting in the ICER of $64,337.49/QALY, which is higher than the WTP threshold. And ICERs were always beyond the WTP threshold of all subgroups. Sensitivity analyses demonstrated the model results were robust. Toripalimab plus axitinib was unlikely to be the cost-effective first-line therapy for patients with previously untreated advanced RCC compared with sunitinib from the Chinese healthcare system perspective. [ABSTRACT FROM AUTHOR]

Background: Locoregionally advanced nasopharyngeal carcinoma (NPC) is an epithelial malignancy that primarily occurs in East and Southeast Asia, and it is associated with relatively poor overall survival (OS). Currently, there is no reliably effective standard treatment for NPC that progresses after first-line therapy with platinum-based chemotherapy. Case report: A 55-year-old woman diagnosed with stage IVa NPC received two cycles of platinum-based chemotherapy but encountered an increase in the size of cervical lymph nodes and suffered from adverse events. The patient was then switched to toripalimab plus cetuximab combined with radical radiotherapy and had a complete clinical response within 2 months following the completion of radiotherapy without severe treatment-related adverse events. Conclusion: This case report showed that toripalimab plus cetuximab combined with radiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma may result in a fast and durable response with a manageable safety profile. [ABSTRACT FROM AUTHOR]

Background: Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM‐NPC), representing a significant milestone as the first FDA‐approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost‐effectiveness of toripalimab for RM‐NPC patients in the American context. Methods: To assess the cost‐effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3‐state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER‐02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results. Results: The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy‐only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness‐to‐pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost‐effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost‐effective unless its price increases by 125%. Additionally, a simulated 15‐year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD‐L1 positive and $70,158/QALY for PD‐L1 negative groups. Conclusions: Toripalimab in combination with chemotherapy is likely to be a cost‐effective alternative to standard chemotherapy for American patients with RM‐NPC. This evidence can guide clinical and reimbursement decision‐making in treating RM‐NPC patients. [ABSTRACT FROM AUTHOR]

Summary: Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I–IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8–46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9–62.8) and 35.7% (95% CI 23.8–53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43–42.54, P

ObjectiveThis study focuses on assessing the cost-effectiveness of incorporating toripalimab alongside chemotherapy for the treatment of patients diagnosed with metastatic triple-negative breast cancer from the perspective of the Chinese healthcare system.MethodsA partitioned survival model was constructed to simulate the costs and health outcomes over the lifetime of patients with mTNBC. Clinical data regarding overall survival, progression-free survival, and treatment-related adverse events were derived from the TORCHLIGHT clinical trials. Incremental cost-effectiveness ratio (ICER) were calculated based on the gains in quality-adjusted life-year (QALY). The willingness-to-pay (WTP) threshold was defined as $39,855.79 per QALY. Additionally, sensitivity analyses were conducted to examine the robustness of the model.ResultsThe total cost incurred by the group receiving toripalimab was $38,040.62, while the placebo plus chemotherapy was $26,102.07. The utilization of the toripalimab regimen resulted in an increase of 0.74 QALYs and an incremental cost of $11,938.55 compared to the placebo plus chemotherapy group. The ICER was $16,133.18/QALY, indicating that toripalimab plus chemotherapy is a cost-effective strategy according to the WTP threshold. Sensitivity analyses confirmed the robustness of the results.ConclusionThis study suggests that the addition of toripalimab to chemotherapy for the treatment of mTNBC is a cost-effective strategy. The findings provide valuable evidence to guide decision-making regarding treatment selection for patients with mTNBC in China.

Objective To investigate the application and effects of apatinib mesylate combined with programmed death receptor-1 (PD-1) monoclonal antibody (mAb)—toripalimab in immunotherapy for triple negative breast cancer (TNBC). Methods Among 40 female BALB/C mice, 8 mice were randomly selected as the blank group without tumor inoculation, and the remaining 32 mice were inoculated with 4T1 cells to establish TNBC models. They were randomly divided into toripalimab group (n=8, administered 10 mg/kg of toripalimab through the tail vein on the 3rd, 6th, and 9th day)， apatinib group (n=8, received 60 mg/kg of apatinib mesylate by gavage daily for 21 consecutive days), combination group (n=8, administration route and dose of apatinib mesylate and toripalimab were the same as those of each single drug group), and model group (n=8, administered normal saline with same volume as administration groups by gavage and tail vein injection at the same time points). The changes of tumor weight and tumor volume in mice were monitored, the pathological changes of tumor in situ and liver/lung metastases in each group were analyzed by HE method, and the markers expressions of CD8+T lymphocytes, myeloid-derived suppressor cells (MDSCs), M2 tumor-associated macrophages (M2-TAMs) and regulatory T cells (Tregs) in the tumor tissues of mice in each group were analyzed by flow cytometry. Results (1) in situ tumors: the volume of in situ tumors in all three administration groups of mice was smaller than that in model group (P＜0.01), while that was smaller in combined group compared with apatinib group and toripalimab group (P＜0.01). Based on model group, the tumor inhibition rates of apatinib group, toripalimab group and combination group increased by (20.3±0.9)%, (24.5±1.2)% and (52.9±0.8)%, respectively, with the highest in combination group (F=997.528, P＜0.01). Pathology showed that the apoptosis phenomenon of in situ tumor cells in combination group was the most significant. (2) Lung/liver metastases: the pathology showed that combination group had the smallest area of lung metastases and the fewest number of liver metastases. (3) Immune cells: compared with the other three groups, the proportion of immune promoting cells (CD8+T cells) in the tumor tissue of combination group significantly increased (P＜0.05), while the proportion of immunosuppressive cells (MDSCs, M2-TAMs, and Tregs cells) significantly reduced (P＜0.05). Conclusion The combination of apatinib mesylate and toripalimab in the treatment of TNBC mice may inhibit the growth of in situ tumor and the formation of lung/liver metastasis formation, and significantly improve the immune efficacy by increasing the proportion of intratumoral immune-promoting cells and reducing the proportion of immunosuppressive cells.

Background: The large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment. Case presentation: We report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence. Conclusions: We reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease. [ABSTRACT FROM AUTHOR]

Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the real-world clinical efficacy and safety, economic burdens and medical resource utilization (MRU) of toripalimab treatment patterns compared with bevacizumab plus chemotherapy (BCP) for patients with advanced non-squamous NSCLC in China. Progression-free survival (PFS), adverse drug reactions (ADR) and the costs of drugs, laboratory testing, imageology examinations (including CT, B ultrasound, MRI), medical service, nursing, treatment, genetic test and medical disposable material were compared between two groups. A retrospective observational study was conducted with electronic medical records from Fudan University Huashan hospital. Data was obtained from established electronic medical records (EMRs) and patient surveys. Survival time from the study enrollment to disease progression or death plus from 1st progression disease (PD) in the maintenance phase to 2nd PD (PFS II), adverse events (AE), direct medical costs, MRU and AE-related costs were collected and compared between toripalimab group and BCP group. A total of 246 patients were enrolled. Toripalimab combination therapy has significantly prolonged PFS comparing with BCP (13.8 months vs. 6.2 months, p <.001). A statistically significant improvement in PFS was observed favoring all toripalimab regimen subgroups compared with the bevacizumab group. Patients in toripalimab group occupied more overall resource consumption, more direct medical costs ($47,056.9 vs. $29,951.0, p <.0001) and AE-related costs ($4,500.2 vs. $784.4, p <.0001) than BCP group. Although patients in the toripalimab group used more drugs to prevent AEs ($4,500.2 vs. $784.4, p <.0001), they still experienced more AEs than patients in BCP group (51.4% vs. 41.4%). Toripalimab combination therapy could significantly prolonged PFS for patients with advanced non-squamous NSCLC compared with BCP, but at the expense of more MRU, costs and AEs. [ABSTRACT FROM AUTHOR]

The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy. • This is a phase II clinical trial of neoadjuvant therapy in patients with resectable mucosal melanoma. • A promising pathologic response rate of 33.3% and a median recurrence-free survival of 11.7 months in responders. • Infiltration of CD3+/CD8+ T cells after neoadjuvant therapy was associated with pathologic response. • J Clin Oncol The neoadjuvant regimen appears to prolong survival while maximizing the preservation of organ function in mucosal melanoma. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab–axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab–axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab–axitinib group and 58.6% of patients in the sunitinib group. In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile ClinicalTrials.gov NCT04394975 • Toripalimab plus axitinib provided significantly better PFS than sunitinib as a first-line treatment for advanced RCC. • A significantly higher ORR was found in patients who received toripalimab plus axitinib than those who received sunitinib. • The combination of toripalimab plus axitinib was generally well tolerated. • No new safety signals were identified in the combination outside the known safety profile of toripalimab or axitinib. [ABSTRACT FROM AUTHOR]

The aim of the current analysis was to evaluate the cost-effectiveness of toripalimab plus chemotherapy compared with chemotherapy alone as the first-line option for patients with advanced esophageal squamous cell carcinoma (ESCC) from the perspective of Chinese health-care system. A partitioned survival model was conducted to track 3-week patients' transition and evaluate the health and economic outcomes in 10-year horizon of the two competing first-line treatment among toripalimab plus chemotherapy and chemotherapy alone. The survival data were gathered from the JUPITER-06 trial, and cost and utility values were obtained from the local charges and published studies. Total costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were the model outcomes. Sensitivity and subgroup analyses were conducted. Treatment with toripalimab plus chemotherapy yields marginal cost of $8,639.74 and additional 0.65 QALYs, resulting in an ICER of $13,280.97 per additional QALY gained, which was lower than the willingness-to-pay (WTP) threshold of $38,224 in China. Sensitivity and subgroup analyses confirmed the robustness of the model outcomes. Toripalimab plus chemotherapy was likely to be the cost-effective first-line option for patients with advanced ESCC compared with chemotherapy alone with the WTP threshold of $38,224 per additional QALY gained from the perspective of the Chinese health-care system. [ABSTRACT FROM AUTHOR]

Background: Toliparibizumab in combination with nab-paclitaxel (T+N) has excellent efficacy inmetastatic or recurrent triple-negative breast cancer (TNBC), but the optimal choice of sequence of therapy is unclear given the trade-offs between quality of life and cost. Cost-effectiveness analyses can quantify these tradeoffs, leading to more informed decisions. Our objective was to assess the societal cost-effectiveness of the T+N regimen for metastatic or recurrent TNBC. Methods: Clinical data were extracted from a multicenter, randomized, double-blind trial, TORCHLIGHT (NCT04085276). Patients were randomized into the T +N group or placebo plus nab-paclitaxel (P+N) group. 531 patients from 53 study locations were randomly assigned (T+N, n=353; P+N, n=178) into intend to treat (ITT) population; 200 and 100 patients, respectively had programmed death protein 1 (PD-L1) positive TNBC. A Markov model was established with a 21-day cycle length. Costs were acquired from local hospitals, effect parameters included quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). Results: The cost differences were 47,538.3 CNY in ITT population (T+N, 143,725.67 CNY; P+N group, 96,187.37 CNY) and 29,258.84 CNY in PD-L1+ subgroup (T+N, 100,128.28 CNY; P+N group, 70,869.45 CNY). Meanwhile, the IEs were 0.03409 in the ITT population (T+N, 0.55323 QALY; P+N, 0.51914 QALY) and 0.03409 in the PD-L1+ subgroup (T+N, 0.42327 QALY; P+N, 0.37628 QALY). The ICERs between T+N and P+N groups were 1,394,548.41 CNY/QALY in the ITT population and 622,663.98 CNY/QALY in the PD-L1+ subgroup. We also analyzed the cost-effectiveness of toripalimab could be received in the Chinese medical insurance catalog. If toripalimab could be reimbursed at an 80% rate, the cost differences were changed to 16,598.99 CNY in ITT population (T+N, 112,786.36 CNY; P+N group, 96,187.37 CNY) and 7,704.58 CNY in PD-L1+ subgroup (T+N, 78,574.03 CNY; P+N group, 70,869.45 CNY). Meanwhile, the IEs remained unchanged. The ICERs between T+N and P+N groups were changed to 486,935.82 CNY/QALY in the ITT population and 163,962.96 CNY/QALY in the PD-L1+ subgroup. Sensitivity analyses indicated the stability of the model and the impact of utility. Conclusion: At current drug prices, the T+N group is not more cost-effective than the P+N group, but after incorporating toripalimab into medical insurance, the T+N group will be more cost-effective for patients with PD-L1+ metastatic or recurrent triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM‐NPC), representing a significant milestone as the first FDA‐approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost‐effectiveness of toripalimab for RM‐NPC patients in the American context. Methods To assess the cost‐effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3‐state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER‐02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results. Results The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy‐only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness‐to‐pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost‐effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost‐effective unless its price increases by 125%. Additionally, a simulated 15‐year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD‐L1 positive and $70,158/QALY for PD‐L1 negative groups. Conclusions Toripalimab in combination with chemotherapy is likely to be a cost‐effective alternative to standard chemotherapy for American patients with RM‐NPC. This evidence can guide clinical and reimbursement decision‐making in treating RM‐NPC patients.

Abstract Objective The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti‐PD‐1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. Methods Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow‐up ends in April 2022. The study’s main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi‐square tests, Kaplan‐Meier, and Cox proportional hazards models were utilized to analyze the data. Results The median follow‐up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti‐PD‐1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child‐Pugh grade A (HR: 0.38, p = 0.032). Conclusions Combining RFA with anti‐PD‐1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone.

Toripalimab, a specific immune checkpoint inhibitor targeting the programmed death 1 (PD-1) receptor, represents a novel immunotherapeutic approach for advanced nasopharyngeal carcinoma, showing promising curative potential. However, it is not without drawbacks, as some patients experience immunerelated adverse events (irAEs) associated with this treatment, and there remains a limited body of related research. Here, we present a case of advanced nasopharyngeal carcinoma in a patient who developed colitis as an irAE attributed to Toripalimab. Subsequent to Toripalimab treatment, the patient achieved complete remission. Notably, the development of colitis was accompanied by inflammatory manifestations evident in colonoscopy and pathology results. Further investigation revealed cytomegalovirus (CMV) infection, detected through immunohistochemistry in 11 colon biopsies. Subsequent treatment with ganciclovir and steroids resulted in symptom relief, and colonoscopy indicated mucosal healing. Our case highlights the association between irColitis induced by Toripalimab and CMV infection. Toripalimab demonstrates remarkable efficacy in treating advanced nasopharyngeal carcinoma, albeit with a notable risk of irAEs, particularly in the form of colitis. The link between symptoms and endoscopic pathology findings in irColitis is noteworthy. Standardized biopsy procedures can effectively confirm the diagnosis of CMV infection. Our findings may provide valuable guidance for managing acute CMV infection and irAEs associated with Toripalimab in the treatment of nasopharyngeal carcinoma in the future. [ABSTRACT FROM AUTHOR]

Melanoma is a fatal malignant tumor with a high rate of metastasis. Liver metastasis of melanoma is always associated with insensitivity to immunotherapy and a poor prognosis. However, the combination of cryoablation, which is believed to stimulate the antitumor immune response in the body, with immunotherapy can improve the therapeutic response to this condition. Herein, we present the case of a 79-year-old woman with BRAF (B-Raf proto-oncogene) wild-type melanoma who later developed liver metastasis. The patient received intravenous antiprogrammed cell death 1 antibody, which showed poor efficacy, and subsequent treatment with immunotherapy combined with cryoablation yielded a partial response. However, after the second cryoablation, the patient refused further treatment due to a fear of bleeding. Therefore, only immunotherapy was provided, which resulted in disease progression. This report demonstrates the need to consider immunotherapy plus cryoablation for the treatment of liver metastases in patients with BRAF wild-type melanoma. [ABSTRACT FROM AUTHOR]

Background: For patients with unresectable hepatocellular carcinoma (HCC), the first-line therapeutic options are still relatively limited, and treatment outcomes remain poor. We aimed to assess the efficacy and safety of anlotinib combined with toripalimab as first-line therapy for unresectable HCC. Methods: In this single-arm, multicenter, phase II study (ALTER-H-003), patients with advanced HCC without previous systemic anticancer therapy were recruited. Eligible patients were given anlotinib (12 mg on days 1-14) combined with toripalimab (240 mg on day 1) in a 3-week cycle. The primary endpoint was the objective response rate (ORR) by immune-related Response Evaluation Criteria in Solid Tumours (irRECIST)/RECIST v1.1 and modified RECIST (mRECIST). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between January 2020 and Jul 2021, 31 eligible patients were treated and included in the full analysis set. At data cutoff (January 10, 2023), the ORR was 29.0% (95% CI: 12.1%-46.0%) by irRECIST/RECIST v1.1, and 32.3% (95% CI: 14.8%-49.7%) by mRECIST criteria, respectively. Confirmed DCR and median DoR by irRECIST/RECIST v1.1 and mRECIST criteria were 77.4 % (95% CI: 61.8%-93.0%) and not reached (range: 3.0-22.5+ months), respectively. Median PFS was 11.0 months (95% CI: 3.4-18.5 months) and median OS was 18.2 months (95% CI: 15.8-20.5 months). Of the 31 patients assessed for adverse events (AEs), the most common grade ≥ 3 treatment-related AEs were hand-foot syndrome (9.7%, 3/31), hypertension (9.7%, 3/31), arthralgia (9.7%, 3/31), abnormal liver function (6.5%, 2/31), and decreased neutrophil counts (6.5%, 2/31). Conclusions: Anlotinib combined with toripalimab showed promising efficacy and manageable safety in Chinese patients with unresectable HCC in the first-line setting. This combination therapy may offer a potential new therapeutic approach for patients with unresectable HCC. First-line therapeutic options for patients with unresectable hepatocellular carcinoma are limited, and treatment outcomes are poor. This article assesses the efficacy and safety of anlotinib combined with toripalimab as first-line therapy for unresectable hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: The treatment paradigm for advanced non-small-cell lung cancer (NSCLC) is rapidly changing. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anti-programmed death-1 (PD-1) antibodies have increasingly been incorporated into routine care for nearly all patients with NSCLC. Toripalimab was recently approved as the first-line treatment for advanced non-squamous NSCLC in combination with chemotherapy. Stevens--Johnson syndrome (SJS) is a rare but potentially fatal complication of TKI and anti-PD-1 therapy. We reported a case of SJS after sequential use of EGFRTKIs and toripalimab in an NSCLC patient with EGFR mutations 19 del/T790M/ C797S in trans and cis. Case presentation: A 58-year-old man with stage IV NSCLC received gefitinib because next-generation sequencing (NGS) revealed an EGFR 19del, followed by osimertinib and pemetrexed with the emergence of EGFR T790M. Four EGFR mutations 19 del/T790M/C797S in trans and cis were detected after osimertinib resistance. The combination of toripalimab and docetaxel was administered as a third-line treatment. The patient developed SJS at 21 days, and toripalimab was discontinued. After treatment with methylprednisolone and prednisolone, the skin toxicity of the patient gradually decreased and eventually disappeared. The patient received osimertinib and anlotinib after recovery, and SJS has not recurred. The ongoing treatment is still effective and results in stable disease. Conclusion: We reported the first case of SJS induced by toripalimab in a patient with lung adenocarcinoma harboring multiple EGFR mutations. The TKI treatment after SJS was well tolerated and effective. [ABSTRACT FROM AUTHOR]

Introduction: This study examined the cost-effectiveness of first-line toripalimab plus chemotherapy (TC) for patients with advanced non-small cell lung cancer (NSCLC), excluding patients with nonsquamous NSCLC and EGFR/ALK mutations. It further analyzed the cost-effectiveness of this strategy in biomarker-based subgroups, all within the context of the Chinese healthcare system. Methods: Eighteen Markov models with 21-day Markov cycle lengths and 30-year time horizons were constructed in this study. Clinical effectiveness data were derived from the CHOICE-01 trial. Health state utilities and costs data were obtained from various sources. The primary outputs were the calculation of incremental cost-effectiveness ratios (ICERs), which were then compared to a willingness-to-pay (WTP) threshold of $17,961 per quality-adjusted life-year (QALY). This comparison was used to determine the treatment that offered greater cost-effectiveness. To account for uncertainty in the model, sensitivity analyses were conducted. Results: For the overall patient population, the estimated ICER between first-line TC and placebo plus chemotherapy (PC) was $9445/QALY, significantly lower than the WTP threshold used in the model. In subgroups based on pathologic types, first-line TC had an ICER of $16,757/QALY for patients with nonsquamous NSCLC, slightly below the WTP threshold; first-line TC demonstrated dominance in patients with squamous NSCLC, indicating both better effectiveness and lower costs compared to first-line PC. In biomarkers-based subgroups, first-line TC was dominant over first-line PC in the subgroups with programmed cell death ligand 1 (PD-L1) expression ≥ 50% and SMARCA4 mutations. Moreover, first-line TC had ICERs lower than the WTP threshold in other subgroups, except for the subgroup with RB1 mutations. Sensitivity analysis confirmed the robustness of these findings. Conclusion: From the perspective of the Chinese healthcare system, this study's findings suggested that first-line TC represents a cost-effective strategy for patients with advanced NSCLC. However, the cost-effectiveness of first-line TC varied across different subgroups when considering predictive biomarkers. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti‐PD‐1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. Methods: Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow‐up ends in April 2022. The study's main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi‐square tests, Kaplan‐Meier, and Cox proportional hazards models were utilized to analyze the data. Results: The median follow‐up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti‐PD‐1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child‐Pugh grade A (HR: 0.38, p = 0.032). Conclusions: Combining RFA with anti‐PD‐1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone. [ABSTRACT FROM AUTHOR]

Objectives: Recently updated results of randomized clinical trials (RCTs) have confirmed that toripalimab, camrelizumab, and tislelizumab plus chemotherapy (TOGP, CAGP, and TIGP) significantly prolonged survival compared to placebo plus chemotherapy (PLGP) in the first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M‐NPC). However, the high cost of immunotherapies imposes a huge financial burden on patients and health care systems. Materials and methods: RCTs estimating immunotherapies for R/M‐NPC were searched. A Bayesian network meta‐analysis (NMA) was carried out; the main outcomes were hazard ratios (HRs) of overall survival (OS) and progression‐free survival (PFS). The cost and efficacy of four first‐line therapies were evaluated using the Markov model. The main outcome in the cost‐effectiveness analysis (CEA) was incremental cost‐utility ratios (ICURs). The model robustness was assessed by one‐way, three‐way, and probabilistic sensitivity analyses. Results: Three RCTs (JUPITER‐02, CAPTAIN‐1st, and RATIONALE‐309) involving 815 patients were included in the NMA. Compared with PLGP, chemo‐immunotherapies have significantly longer PFS and OS. Compared to the PLGP group, TOGP, CAGP, and TIGP groups resulted in additional costs of $48 339, $22 900, and $23 162, with additional 1.89, 0.73, and 0.960 QALYs, respectively, leading to the ICURs of $25 576/QALY, $31 370/QALY, and $31 729/QALY. Pairwise comparisons showed TOGP was the most cost‐effective option among chemo‐immunotherapy groups. Conclusion: From the Chinese payers' perspective, first‐line immunotherapy combination therapies provided significant survival and cost‐effectiveness superiority over chemotherapy alone for patients with R/M‐NPC at the WTP of $38 029/QALY. Among the three chemo‐immunotherapy groups, TOGP was the most cost‐effective option. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the cost-effectiveness of toripalimab versus Chemotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC) from the perspective of the Chinese healthcare system. A partitioned survival model was designed. Clinical data on survival was taken from the JUPITER-06 trials. Direct medical expenditures and utilities were gathered from published literature and a local database. One-way and probability sensitivity methods were used to evaluate the model's robustness. Compared with chemotherapy alone, toripalimab offered an incremental cost of $8950.427 with an additional 0.294 QALYs, yielding an ICER of 30,443.629$/QALYs first-line therapy for advanced ESCC. The ICER was below the threshold of willingness to pay in China, indicating that the toripalimab group had a cost-effective advantage. Sensitivity analysis showed that the ICERs were most sensitive to the utility of PD, but all the parameters had no significant impact on the model's outcomes. Toripalimab may be a cost-effective first-line treatment choice in our research when compared to chemotherapy alone for patients with advanced ESCC. [ABSTRACT FROM AUTHOR]

Abstract Background Immune checkpoint inhibitor (ICI) combined with chemotherapy has exhibited promising results in small sample studies of pancreatic cancer patients. The efficacy of toripalimab, a programmed cell death protein 1 (PD-1) monoclonal antibody has been explored in the previous studies and it was established that immune-related adverse events (irAEs) associated with administration of this drug deserve proper attention and adequate management. Case presentation A 43-year-old female patient with advanced pancreatic ductal adenocarcinoma (PDAC) was treated with toripalimab in combination with gemcitabine and nab-paclitaxel (T-GA) as the first-line treatment. She developed immune-related encephalopathy with stuttering as the main clinical symptom and Magnetic resonance imaging (MRI) showed multiple cerebral white matter demyelination changes, concomitant with asymptomatic cardiac enzyme elevation and hypothyroidism. The symptoms resolved after the discontinuation of toripalimab and corticosteroid treatment. Conclusions Stuttering might be an early sign of neurotoxicity which can be easily neglected during the treatment. These findings provide guidance for the identification of these rare and occult neurological irAEs (n-irAEs) in the clinical practice.

Background: Toripalimab is the first domestic anti-tumor programmed death 1 antibody marketed in China. The CHOICE-01 trial (identifier: NCT 03856411) demonstrated that toripalimab plus chemotherapy can significantly improve the clinical outcomes of advanced non-small cell lung cancer (NSCLC) patients. However, whether it is cost-effective remains unknown. Given the high cost of combination therapy, a cost-effectiveness analysis of toripalimab plus chemotherapy (TC) versus chemotherapy alone (PC) for the first-line treatment of patients with advanced NSCLC is required. Methods: A partitioned survival model was adopted to predict the course of disease in advanced NSCLC patients on TC or PC from the perspective of the Chinese healthcare system over a 10-year horizon. The survival data were obtained from the CHOICE-01 clinical trial. Cost and utility values were obtained from local hospitals and kinds of literature. Based on these parameters, the incremental costeffectiveness ratio (ICER) of TC vs. PC was measured, and one-way sensitivity analyses, probabilistic sensitivity analyses (PSA), and scenario analyses were performed to assess the robustness of the model. Results: In the base case, TC was associated with an incremental cost of $18510 and an incremental quality-adjusted life year (QALY) of 0.57 compared with PC, resulting in an ICER of $32237/QALY which was lower than the willingness to pay (WTP) threshold ($37654/QALY), TC was cost-effective. The health utility value of progression-free survival, the price of toripalimab, and the cost of best supportive care were factors that significantly influenced the ICER, but no change in any of them could change the model result. TC showed a 90% probability of being a cost-effective option at a WTP threshold of $37,654/QALY. In the 20 and 30-year time horizons, the results remained unchanged and TC remained cost-effective when the second-line treatment was switched to docetaxel. Conclusion: At a WTP threshold of $37,654 per QALY, TC was cost-effective compared to PC for patients with advanced NSCLC in China. [ABSTRACT FROM AUTHOR]

Background: Toripalimab is an immune checkpoint inhibitor (ICI) against programmed death ligand 1 (PD-L1). It has been approved for advanced esophageal squamous cell carcinoma (ESCC) as the first-line treatment due to significantly improved progression-free survival (PFS) and overall survival (OS) in the JUPITER-06 trial. Aim: This study aimed to compare the cost-effectiveness between toripalimab plus chemotherapy and placebo plus chemotherapy from the perspective of the Chinese health system. Method: The study developed a 3-year partitioned survival model to assess costs and outcomes in two treatment groups with or without toripalimab. The critical indicator was the incremental cost-effectiveness ratio (ICER). Scenario and sensitivity analyses were performed to evaluate the robustness of the findings and identify the parameters with the greatest impact on cost-effectiveness. Results: In the base case analysis, the incremental effectiveness and cost of toripalimab plus chemotherapy versus placebo plus chemotherapy were 0.26 quality-adjusted life year (QALYs) and $11,254.84, respectively, resulting in an ICER of $43,405.09/QALY, higher than the 2021 willingness-to-pay threshold in China ($37,658.70/QALY). The results were sensitive to the utility of PFS, the incidence of neutropenia in the toripalimab group, and the cost of toripalimab. The toripalimab plus chemotherapy group was cost-effective only if the price of toripalimab decreased by more than 40%. Conclusion: Adding toripalimab to chemotherapy was not cost-effective in patients with advanced ESCC in China. [ABSTRACT FROM AUTHOR]

Objectives: The results of a CHOICE-1 study demonstrated the superior efficacy of toripalimab (anti-PD-1 antibody) plus chemotherapy for patients with advanced non--small cell lung cancer (NSCLC), with a manageable safety profile. This study was performed to evaluate the economic value of this treatment for this patient population from the Chinese payer's perspective. Materials and methods: Basic data were derived from the CHOICE-1 study. Markov models were developed to simulate the process of advanced NSCLC, including the progression-free survival (PFS), progressive disease (PD), and death in intention-to-treat (ITT) populations, as well as patients with squamous or nonsquamous NSCLC. The cost was obtained from the local institution, and the value of utilities referred to previous studies. Monte Carlo simulations were performed to depict the probabilistic scatter plots of the incremental cost-effectiveness ratio (ICER) and acceptability curves, aiming to address the uncertainty of model inputs. Results: Compared with standard chemotherapy, toripalimab plus chemotherapy yields an ICER of $21,563 per quality-adjusted life year (QALY) in the ITT population. For patients with squamous NSCLC, comparing the combined therapy with chemotherapy led to an ICER of $18,369 per QALY, while the ICER was $24,754 per QALY in patients with non-squamous NSCLC. With the threshold of willingness to pay we set ($37,653 per QALY), toripalimab plus chemotherapy was cost-effective in these patient populations. Conclusion: For patients with advanced NSCLC, toripalimab plus chemotherapy was an optimal choice as first-line treatment, regardless of histology. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant immunotherapy with anti-PD-1 was proved promising in resectable non-small cell lung cancer (NSCLC). Immune-related adverse events (irAEs) have been preliminarily implicated their association with treatment efficacy. Here we elucidated the early onset of irAEs associated with better clinical outcomes in a prospective study (Renaissance study). Methods: We conducted the prospective study of NSCLC patients treated by neoadjuvant Toripalimab (240mg, every 3 weeks) plus double platinum-based chemotherapy from December 2020 to March 2022 at Peking University Cancer Hospital. Patients were enrolled if they have resectable IIB-IIIB NSCLC without EGFR/ALK mutation. Data were analyzed to explore the relationship between clinical outcome and irAEs after neoadjuvant treatment. A multidisciplinary team including physicians, surgeons, and radiologists, confirmed the irAEs according to the clinical manifestation. The relationship between irAEs and pathological outcomes was analyzed. The Renaissance study was approved by the Peking University Ethic board (2020YJZ58) and registered at https://clinicaltrials.gov/ as NCT04606303. Results: Fifty-five consecutive patients were enrolled with a male-to-female ratio of 10:1, the median age was 62 years old (IQR: 45-76), of which 44 patients (80%) were diagnosed with squamous cell carcinoma. Forty-eight of 55 patients finally received thoracic surgery with a median preoperative waiting time of 67 days (IQR 39-113 days). Pathological results demonstrated that 31 (64.6%) patients achieved major pathological response (MPR) and 24 (50.0%) achieved complete pathological response (pCR). Among 48 patients who received R0 resection, immunotherapyrelated thyroid dysfunction, rash/pruritus and enteritis occurred in 11 patients (22.9%), 7 patients (14.6%), and 1 patient (2.1%), respectively. Six patients (54.5%) with thyroid dysfunction achieved MPR with 5 (45.5%) achieved pCR, and a median time to onset was 45 days (IQR 21-91 days). Six patients (85.7%) with rash or pruritus achieved MPR and 5 patients (71.4%) achieved pCR, with median time to onset being 8 days (IQR 6-29 days). Furthermore, irAEs had no significant influence on operation time (170.6 min vs 165.7 min, P=0.775), intraoperative blood loss (67.4 mL vs 64.3 mL, P=0.831) and preoperative waiting time (93 days vs 97 days, P=0.630) when comparing with patients without irAEs (Figure 1). Conclusion: The immunotherapy-related rash is potentially associated with pathological outcomes in NSCLC patients after neoadjuvant chemoimmunotherapy, suggesting easy-to-find irAEs, such as rash, can be used as indicators to predict response to neoadjuvant chemo-immunotherapy. [ABSTRACT FROM AUTHOR]

Summary: Background: To evaluate the efficacy and safety of toripalimab combined with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: In this single arm, phase II trial, 44 ESCC patients were enrolled from December 2019 to July 2021 at Sun Yat-sen University Cancer Center (Guangzhou, China). All patients received concurrent radiotherapy (44 Gy in 20 fractions), chemotherapy (paclitaxel 50 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, and 22), and toripalimab (240 mg on days 1 and 22). Within 6–8 weeks of neoadjuvant treatment, patients underwent surgery. The results of the study patients were compared with those of 86 matched patients between July 2015 and March 2022. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoints were treatment-related adverse events and R0 rates. This trail was registered with ClinicalTrails.gov, NCT04006041. Findings: All patients received neoadjuvant treatment, and 42 completed esophagectomy. Of the 42 patients, 21 (50%; 95% CI 35–65) achieved pCR and 2 (5%) patients were ypT0N+. The R0 resection rate was 98% (41/42). Nine (20%) of 44 patients had grade 3/4 adverse events. Among the perioperative complications (n = 42), anastomotic leakage occurred in five cases (12%), tracheal fistula in three cases (7%), and postoperative death in one case (2%) due to tracheal fistula. Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, P = 0.19). Interpretation: Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. Nevertheless, considering the signs of efficacy and acceptable safety of this regimen, further evaluation in phase III randomized trials might be warranted. Funding: National Natural Science Foundation of China.

Abstract Background Concurrent chemoradiotherapy is currently the standard of care for patients with locally advanced cervical cancer. However, even with the application of modern radiotherapy techniques, a considerable number of patients still develop distant metastases. PD-L1 inhibitors show good efficacy in cervical cancer. This single-arm phase II study aims to explore the efficacy and tolerability of combining PD-L1 inhibitor with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. Methods/design The primary endpoint of the study was the objective response rate assessed according to RECIST v1.1 criteria. The inclusion criteria were previously untreated patients aged 18–75 years with stage III-IVA (FIGO 2018 staging system) locally advanced cervical cancer. During concurrent chemoradiotherapy and consolidation chemotherapy, the enrolled patients will receive toripalimab (240 mg) every 3 weeks. After consolidation chemotherapy, the enrolled patients will be treated with toripalimab (240 mg) once every 6 weeks until the whole treatment cycle reaches 1 year. Intensity modulated radiotherapy was used for external beam radiation, and high-dose rate brachytherapy was delivered under image-guidance. Weekly DDP (40 mg/m2) was given concurrently with radiotherapy while 6 cycles of consolidated chemotherapy (paclitaxel plus DDP) were given after radiotherapy every three weeks. Secondary objectives included safety and tolerability, toxicity profile, progression-free survival, and overall survival. Discussion PD-L1 inhibitor has shown good efficacy in recurrent/metastatic cervical cancer. However, there is still a lack of evidence about its combination with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. The purpose of this study is to explore the efficacy and tolerance of this combination therapy, so as to lay the foundation for the future phase III randomized study. Trial registration clinicaltrials.gov NCT05084677 . Retrospectively registered on Octorber 07, 2021.

BackgroundNeoadjuvant immunotherapy with anti-PD-1 was proved promising in resectable non-small cell lung cancer (NSCLC). Immune-related adverse events (irAEs) have been preliminarily implicated their association with treatment efficacy. Here we elucidated the early onset of irAEs associated with better clinical outcomes in a prospective study (Renaissance study).MethodsWe conducted the prospective study of NSCLC patients treated by neoadjuvant Toripalimab (240mg, every 3 weeks) plus double platinum-based chemotherapy from December 2020 to March 2022 at Peking University Cancer Hospital. Patients were enrolled if they have resectable IIB-IIIB NSCLC without EGFR/ALK mutation. Data were analyzed to explore the relationship between clinical outcome and irAEs after neoadjuvant treatment. A multidisciplinary team including physicians, surgeons, and radiologists, confirmed the irAEs according to the clinical manifestation. The relationship between irAEs and pathological outcomes was analyzed. The Renaissance study was approved by the Peking University Ethic board (2020YJZ58) and registered at https://clinicaltrials.gov/ as NCT04606303.ResultsFifty-five consecutive patients were enrolled with a male-to-female ratio of 10:1, the median age was 62 years old (IQR: 45-76), of which 44 patients (80%) were diagnosed with squamous cell carcinoma. Forty-eight of 55 patients finally received thoracic surgery with a median preoperative waiting time of 67 days (IQR 39-113 days). Pathological results demonstrated that 31 (64.6%) patients achieved major pathological response (MPR) and 24 (50.0%) achieved complete pathological response (pCR). Among 48 patients who received R0 resection, immunotherapy-related thyroid dysfunction, rash/pruritus and enteritis occurred in 11 patients (22.9%), 7 patients (14.6%), and 1 patient (2.1%), respectively. Six patients (54.5%) with thyroid dysfunction achieved MPR with 5 (45.5%) achieved pCR, and a median time to onset was 45 days (IQR 21-91 days). Six patients (85.7%) with rash or pruritus achieved MPR and 5 patients (71.4%) achieved pCR, with median time to onset being 8 days (IQR 6-29 days). Furthermore, irAEs had no significant influence on operation time (170.6 min vs 165.7 min, P=0.775), intraoperative blood loss (67.4 mL vs 64.3 mL, P=0.831) and preoperative waiting time (93 days vs 97 days, P=0.630) when comparing with patients without irAEs (Figure 1).Figure 1Comparison of operation time (A), intraoperative blood loss (B), and preoperative waiting time (C) between “with irAEs” and “without irAEs”.ConclusionThe immunotherapy-related rash is potentially associated with pathological outcomes in NSCLC patients after neoadjuvant chemo-immunotherapy, suggesting easy-to-find irAEs, such as rash, can be used as indicators to predict response to neoadjuvant chemo-immunotherapy.Clinical trial registrationclinicaltrials.gov/, identifier NCT04606303.

Epithelioid hemangioendotheliomas (EHEs), low-grade malignant tumors of vascular endothelial cell origin, are characterized by vascular endothelial proliferation. In 2002, the World Health Organization classified EHEs as locally aggressive tumors with the potential to metastasize. Currently, the diagnosis of EHE is based on pathology, histological and immunohistochemical examinations. There are no standard treatment guidelines. We here report a 69-year-old man who presented with left-sided chest and abdominal pain for more than 2 months. Enhanced computed tomography of the thorax and abdomen in another hospital suggested a mass in the left adrenal region that was considered malignant. Positron emission tomography-computed tomography in our hospital suggested a large multi-loculated, hypermetabolic, cystic mass in the left adrenal region that was considered malignant. Accordingly, a puncture biopsy of the mass was performed and the diagnosis of EHE confirmed by pathological examination, including immunohistochemical staining. This patient was treated with the programmed death 1 (PD-1) immune checkpoint inhibitor toripalimab with long-term success. The best response was stable disease (SD) with a progression-free survival (PFS) of more than 13 months. The patient is still alive now. Because the sample size of previous studies was small, further studies are needed to determine the safety and efficacy of toripalimab in the treatment of EHE. [ABSTRACT FROM AUTHOR]

Objective: Exposing tumor antigens to the immune system is the key to ensuring the efficacy of immunotherapy. SBRT is the main way to reveal the specifical antigens of tumors which can enhance the immune response. We aimed to explore the clinical efficacy and safety of Toripalimab combined with Anlotinib for uHCC after SBRT. Methods: This is a prospective, single-arm, explorative clinical study. uHCC patients with an ECOG PS score of 0–1, Child–Pugh class A or B, and BCLC stage B or C were included and treated with SBRT(8Gy*3) followed by 6-cycle combinational therapy with Toripalimab and Anlotinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of treatment-related adverse events (TRAEs). Continuous variables were presented as medians and ranges. Survivals were studied with the KaplanMeier method. Categorical data were expressed as n (percentage). Results: Between June 2020 and October 2022, a total of 20 patients with intermediate-advanced uHCC were enrolled. All cases had multiple intrahepatic metastases, or macrovascular invasion, or both, among whom 5 cases with lymph node or distant metastases. Until September 2022, the median follow-up time was 7.2 months (range, 1.1-27.7 months). Median survival time could not be assessed at the moment, based on iRecist, median PFS was 7.4 months (range, 1.1-27.7 months), ORR 15.0%, and DCR 50.0%. 14 patients experienced treatment-related adverse events with an incidence of 70%. The overall survival rates at 18 months and 24 months were 61.1% and 50.9%, respectively. And the progression-free survival rates were 39.3% and 19.7%. Conclusion: Exposure of specific antigens of HCC via SBRT may improve the efficacy of combinational therapy with Toripalimab and Anlotinib for uHCC with manageable adverse effects, which deserves further exploration. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor (ICI) combined with chemotherapy has exhibited promising results in small sample studies of pancreatic cancer patients. The efficacy of toripalimab, a programmed cell death protein 1 (PD-1) monoclonal antibody has been explored in the previous studies and it was established that immune-related adverse events (irAEs) associated with administration of this drug deserve proper attention and adequate management. Case presentation: A 43-year-old female patient with advanced pancreatic ductal adenocarcinoma (PDAC) was treated with toripalimab in combination with gemcitabine and nab-paclitaxel (T-GA) as the first-line treatment. She developed immune-related encephalopathy with stuttering as the main clinical symptom and Magnetic resonance imaging (MRI) showed multiple cerebral white matter demyelination changes, concomitant with asymptomatic cardiac enzyme elevation and hypothyroidism. The symptoms resolved after the discontinuation of toripalimab and corticosteroid treatment. Conclusions: Stuttering might be an early sign of neurotoxicity which can be easily neglected during the treatment. These findings provide guidance for the identification of these rare and occult neurological irAEs (n-irAEs) in the clinical practice. [ABSTRACT FROM AUTHOR]

This study compares first-line toripalimab with chemotherapy for advanced nonsquamous non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. A three-state Markov model was established to compare the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) of first-line toripalimab plus chemotherapy versus chemotherapy. Clinical outcomes data were acquired from the CHOICE-01 clinical trials. Costs and utilities were gathered from regional databases or published publications. One-way sensitivity and probability sensitivity analyses were used to investigate the stability of the model parameters. First-line toripalimab treatment for advanced nonsquamous NSCLC resulted in an incremental cost of $16,214.03 and added 0.77 QALYs compared to chemotherapy, which had an ICER of $21,057.18 per QALY gained. The ICER was substantially lower than the willingness to pay (WTP) threshold in China, which was $37,663.26 per QALY. The toripalimab cycle used was shown to have the greatest impact on the ICERs, according to sensitivity analysis, although none of the factors significantly affected the model's outcomes Toripalimab plus chemotherapy is likely to be a cost-effective option compared with chemotherapy alone for patients with advanced nonsquamous NSCLC from the perspective of the Chinese healthcare system. [ABSTRACT FROM AUTHOR]

Introduction: First-line treatment with toripalimab plus paclitaxel and cisplatin (TTP) is very effective for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) in China, although its effects on economic burden are unknown. The present study aimed to evaluate the cost-effectiveness of TTP from the perspective of the Chinese healthcare system. Methods: A Markov model was established to evaluate the cost-effectiveness of first-line treatment with TTP for patients with advanced or metastatic ESCC. Survival data were derived from the JUPITER-06 trial. The costs and utilities were gathered from the literature and a local database. The primary outcomes were total costs, quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) at a willingness-to-pay (WTP). One-way and probability sensitivity analyses were used to evaluate the robustness of the model. Results: The total cost of TTP was $123,646.43 and gained 1.10 QALYs, while the paclitaxel and cisplatin (TP) chemotherapy group yielded 0.84 QALY at cost of $16,259.65. First-line TTP treatment yielded an incremental cost of $7,386.78 with an additional 0.26 QALY, providing an ICER of $28,348.42/QALY, which was lower than the WTP threshold ($36,257.91) in China. Conclusions: TTP was likely more cost-effective than TP chemotherapy from the perspective of the Chinese healthcare system. This study may provide evidence required to establish decision-making criteria to support guidance for cost-effective selection of an immunotherapeutic regimen. [ABSTRACT FROM AUTHOR]

Purpose: This phase 1 trial evaluated the safety, preliminary efficacy, and pharmacokinetics of surufatinib, a small molecular tyrosine kinase inhibitor, combined with toripalimab, a programmed cell death protein-1 antibody, in patients with advanced solid tumors. Methods: This is an open-label, dose-escalation and expansion study in patients with solid tumors who had failed standard therapies or had no effective treatment. In the dose-escalation stage, patients were treated with surufatinib, at dose levels of 200, 250, or 300 mg once daily (QD) in combination with toripalimab 240 mg, every 3 weeks (Q3W), to estimate maximum tolerated dose. Additional patients were enrolled in the dose expansion stage to further assess the efficacy, safety, and pharmacokinetics profile. Recommended phase 2 dose (RP2D) was determined based on the safety, tolerability, and preliminary efficacy from dose-escalation and expansion stages. Results: From Feb 14, 2019 to Dec 20, 2020, 33 patients were screened, of which 30 patients were enrolled. One patient in the 300 mg cohort experienced dose limited toxicity, a grade 3 hyperthyroidism. The most frequent treatment-related adverse events of grade ≥ 3 were hypertension (20.0%), transaminases increased (13.3%), and blood bilirubin increased (13.3%). No treatment-related death or treatment discontinuation was identified. The RP2D was determined to be surufatinib 250 mg QD plus toripalimab 240 mg Q3W. Objective response rate was 24.1% (95% confidence interval 10.3‒43.5%) in this study. Conclusions: Surufatinib plus toripalimab was well tolerated, with no unexpected safety signals, and showed preliminary anti-tumor activity in patients with advanced solid tumors. Trial registration: Clinicaltrials.gov Identifier: NCT03879057; registration date: March 18, 2019. [ABSTRACT FROM AUTHOR]

Introduction: Flat dosing regimen has recently been approved for programmed death receptor-1 (PD-1) inhibitors including toripalimab, nivolumab and pembrolizumab. The objective of this study is to provide pharmacological evidence for a flat dosing regimen of toripalimab by assessing the efficacy and safety profile of a 240 mg Q3W flat dose relative to the currently approved 3 mg/kg Q2W. Methods: A population pharmacokinetic (PopPK) model was established based on 1,014 evaluable patients in 13 clinical studies. The exposure-objective response rate (ORR, n = 234) and exposure-safety (n = 152) analyses were performed by logistic regression. Three safety endpoints including grade = 3 adverse events (AEs), treatment-related grade = 3 AEs, and AEs leading to study drug discontinuation were evaluated. Progression-free survival (PFS, n = 234) was evaluated using a Cox proportional hazard model with the Kaplan-Meier survival curve. Results: The PK profiles of toripalimab are best described by a two-compartment model with time-varying clearance characterized by a sigmoidal maximum effect (Emax) function. Simulations for the first dose and steady-state exposures for the 240 mg Q3W dosing regimen were comparable to those for the 3 mg/kg Q2W dosing regimen with 95% exposure coverage ranging from 88% to 96%. The exposure-safety analysis showed that the probability of an adverse event occurring did not increase with increases in toripalimab exposure. A flat exposure-response relationship for ORR was identified. The Kaplan-Meier survival curve showed that exposure was a predictor for PFS; however, no difference in treatment benefit was demonstrated across exposure quantiles using a Cox proportional hazard model. Discussion: This study revealed that toripalimab exposure of 240 mg Q3W dosing regimen was comparable to 3 mg/kg Q2W dosing regimen. The safety and efficacy E-R results of 240 mg Q3W is flat. Hence, the 240 mg Q3W dosing regimen is determined to be a preferred therapeutic dosage for toripalimab due to the convenience of flat dose. [ABSTRACT FROM AUTHOR]

Abstract Background Immune checkpoint inhibitors were used for patients with advanced non-small cell lung cancer (NSCLC) more and more frequently and the effects were thrilling. Toripalimab as a new immune checkpoint inhibitor has been shown to be effective in patients with advanced NSCLC. However, data regarding the safety and feasibility of surgical resection after treatment with toripalimab for NSCLC remain scarce. Here, we present a case with locally advanced NSCLC that received video-assisted thoracic surgery (VATS) lobectomy after treatment with toripalimab in combination with chemotherapy. Case presentation A 62-year-old male patient with a history of coronary artery stenting operation for two times was found a 3.4 × 3.2 cm cavity mass in the upper lobe of the left lung and enlarged left hilar and mediastinal lymph nodes. Pathological results identified squamous cell carcinoma. The patient was diagnosed with a locally advanced NSCLC and received VATS left upper lobectomy and lymph node dissection after neoadjuvant chemotherapy plus toripalimab for 3 cycles. The postoperative pathological results showed complete tumor remission. Short-term follow-up results were excellent, and long-term results remain to be revealed. Conclusions Our preliminary results showed that the use of neoadjuvant toripalimab and chemotherapy for the locally advanced NSCLC before surgical resection is safe and feasible.

Background and objectiveThe CHOICE-01 trial showed that toripalimab plus chemotherapy achieved satisfactory outcomes compared with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who were negative for driver genes, but the economics of this regimen is unclear. Therefore, this study aimed to evaluate the cost-effectiveness of toripalimab in combination with chemotherapy in advanced NSCLC with negative driver genes from the perspective of the Chinese healthcare system.Materials and methodsA three-state partitioned survival model was developed to simulate the costs and outcomes associated with adding toripalimab to first-line chemotherapy. The clinical data in the model came from the CHOICE-01 trial, only direct medical costs were included, and utility values were referred to the literature. Four models were applied to explore the differences in the results of fitting and extrapolating K-M curves from different models, and cost-effectiveness subgroup analysis was performed. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the impact of parameter uncertainty on the model.ResultsThe baseline analysis showed that toripalimab coupled with chemotherapy cost $21,052 more than chemotherapy ($43,197 vs. $22,145) and also gained 0.71 QALYs more (1.75 QALYs vs. 1.03 QALYs), with an ICER of $29,478/QALYs. At the current willingness-to-pay threshold ($35,108/QALY), the extra cost was well worth it. The results of fitting and extrapolating the survival curves using other models were consistent with the results of the standard parametric model. Subgroup analysis demonstrated that the addition of toripalimab to chemotherapy was economical. Sensitivity analysis showed that the utility values of PD and PFS stages had the greatest impact on the model.ConclusionFrom the viewpoint of the Chinese healthcare system, toripalimab combined with chemotherapy in the treatment of advanced NSCLC with negative driver genes was likely to be cost-effective compared with chemotherapy.

Background: The potency and safety of toripalimab combination with chemotherapy (TC) as the first-line therapy for advanced non-small cell lung cancer (NSCLC) have been demonstrated in the CHOICE-01 study. Our research explored whether TC was cost-effective compared to chemotherapy alone from the Chinese payer perspective.Materials and methods: Clinical parameters were obtained from a randomized, multicenter, registrational, placebo-controlled, double-blind, phase III trial. Standard fee databases and previously published literature were used to determine costs and utilities. A Markov model with three mutually exclusive health statuses (progression-free survival (PFS), disease progression, and death) was used to predict the disease course. The costs and utilities were discounted at 5% per annum. The main endpoints of the model included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses were performed to investigate the uncertainty. Subgroup analyses were performed to verify the cost-effectiveness of TC in patients with squamous and non-squamous cancer.Results: TC combination therapy yielded an incremental 0.54 QALYs with an incremental cost of $11,777, compared to chemotherapy, giving rise to ICERs of $21,811.76/QALY. Probabilistic sensitivity analysis revealed that TC was not favorable at 1 time GDP per capita. With a prespecified willingness-to-pay threshold (WTP) of three times the GDP per capita, combined treatment had a 100% probability of being cost-effective and had substantial cost-effectiveness in advanced NSCLC. Probabilistic sensitivity analyses showed that TC was more likely to be accepted with a WTP threshold higher than $22,195 in NSCLC. Univariate sensitivity analysis showed that the utility of PFS state, crossover proportions of the chemotherapy arm, cost per cycle of pemetrexed treatment, and discount rate were the dominant influencing factors. Subgroup analyses found that in patients with squamous NSCLC, the ICER was $14,966.09/QALY. In the non-squamous NSCLC, ICER raised to $23,836.27/QALY. ICERs were sensitive to the variance of the PFS state utility. TC was more likely to be accepted when WTP increases exceeded $14,908 in the squamous NSCLC subgroup and $23,409 in the non-squamous NSCLC subgroup.Conclusion: From the perspective of the Chinese healthcare system, TC may be cost-effective in individuals with previously untreated advanced NSCLC at the prespecified WTP threshold compared to chemotherapy, and more significant in individuals with squamous NSCLC, which will provide evidence for clinicians to make the best decisions in general clinical practice.

Our study aimed to explore the efficacy and safety of anlotinib–toripalimab combination therapy as a second-line treatment for advanced relapsed gastric or gastroesophageal junction carcinoma (GC/GEJC). In this single arm, single-center extension clinical trial, patients with advanced relapsed GC/GEJC received toripalimab (240 mg, intravenously over 60 minutes, once every 2 weeks) plus anlotinib (12 mg/day, orally, 2 weeks on and 1 week off, every 3 weeks) as second-line therapy. There were 29 patients who achieved partial response, and the ORR was 32.3% (95% CI, 26.6%-38.5%). Grade 3 treatment-related adverse events (TRAEs) were recorded in 7 participants (11.3%), all of which were manageable. The PFS and OS were 4.0 and 11.1 months, respectively. Patients with programmed death-ligand 1 (PD-L1) positive expression showed numerically longer OS than the negative ones although the difference was not significantly. The tumor mutational burden-high (TMB-H) group showed a significantly better OS (P =.05) than the TMB-Low (TMB-L) group. Next-generation sequencing (NGS) revealed that fibroblast growth factor receptor 2 (FGFR2) mutations positively correlated with target lesion reduction (odds ratio [OR] = 0.14; P =. 02). The new regimen increased tumor-infiltration of CD8+ T and CD3+ T cells. Furthermore, a patient-derived organoid (PDO) study indicated that anlotinib could promote an immune-supportive tumor microenvironment. As conclusion, the anlotinib-toripalimab combination showed promising efficacy and favorable safety as a second-line treatment for advanced, relapsed GC/GEJC. The PD-L1 expression, TMB, and FGFR2 mutation are potential biomarkers for predicting the efficacy of this regimen (ClinicalTrials.gov registration number: NCT04713059). [ABSTRACT FROM AUTHOR]

Introduction: This retrospective study aimed to compare the efficacy and safety of transarterial chemoembolization plus lenvatinib and programmed death 1 (PD-1) inhibitors versus transarterial chemoembolization plus lenvatinib or sorafenib in patients with unresectable hepatocellular carcinoma. Methods: Consecutive patients with unresectable hepatocellular carcinoma who received transarterial chemoembolization plus lenvatinib and PD-1 inhibitors, lenvatinib, or sorafenib were retrospectively identified in our institution between January 2018 and August 2020. The primary endpoint was overall survival. Results: A total of 84 patients were included in this analysis. The median overall survival was significantly improved in the transarterial chemoembolization plus lenvatinib and PD-1 inhibitor group compared with the transarterial chemoembolization plus sorafenib group (26.7 months [95% confidence interval 25.2-31.6] vs 14.4 months [95% confidence interval 9.5-18.9]; hazard ratio 0.39 [95% confidence interval 0.17-0.72]; P =.007) or the transarterial chemoembolization plus lenvatinib group (26.7 months [95% confidence interval 25.2-31.6] vs 17.9 [95% confidence interval 13.4-22.2] months; hazard ratio 0.45 [95% confidence interval 0.17-0.87]; P =.031). Transarterial chemoembolization plus lenvatinib and PD-1 inhibitor also significantly prolonged median progression-free survival compared with transarterial chemoembolization plus sorafenib group (8.2 months [95% confidence interval 3.3-13.0] vs 6.0 months [95% confidence interval 4.2-7.8]; hazard ratio 0.47 [95% confidence interval 0.24-0.74]; P =.005) or the transarterial chemoembolization plus lenvatinib group (8.2 months [95% confidence interval 3.3-13.0] vs 6.6 [95% confidence interval 4.3-7.9] months; hazard ratio 0.58 [95% confidence interval 0.31-0.96]; P =.047). No significant difference was seen between groups in the incidence of an adverse event or grade 3 or higher adverse event. Conclusion: Transarterial chemoembolization plus lenvatinib, and PD-1 inhibitor was associated with better survival benefits and acceptable toxicities, which may provide an additional therapeutic option for unresectable hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

The combination of lenvatinib, toripalimab and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) suggested encouraging antitumour activity in our retrospective study. We hereby prospectively establish the efficacy, safety and predictive biomarkers of the combination therapy as a first-line treatment in patients with high-risk advanced hepatocellular carcinoma (HCC). This phase II, single-centre, single-arm trial enrolled advanced HCC participants with high-risk. Of 51 screened participants, 36 received lenvatinib, toripalimab plus FOLFOX-HAIC. Participants received 21-day treatment cycles of lenvatinib, toripalimab, and FOLFOX-HAIC. The primary end-point was the progression-free survival (PFS) rate per RECIST at six months. Thirty-six participants (86.1% with high-risk features) were enrolled in our study. The primary end-point was met with a PFS rate of 80.6% (95% CI, 64.0%–91.8%) at six months. The median PFS was 10.4 months (95% CI, 5.8–15.0), and the median OS was not reached at the prespecified final analysis and was 17.9 months (95% CI, 14.5–21.3) after follow-up was extended. The ORR per RECIST was 63.9%, and per mRECIST was 66.7%. The median duration of response was 14.4 months (95% CI, 8.9–19.9). The most common adverse events were thrombocytopenia, elevated aspartate aminotransferase, and hypertension, and no treatment-related death was reported. Participants with low levels of both CCL28 and BTC had unsatisfactory prognosis. Lenvatinib, toripalimab and FOLFOX-HAIC showed safe and encouraging antitumour activity for advanced HCC with high-risk features. The levels of CCL28 and BTC might be the predictive biomarkers for the triple combination therapy. • High-risk advanced HCC is associated with poor outcomes of systemic therapy. • Combination FOLFOX-HAIC with lenvatinib and toripalimab was tolerable and effective. • CCL28 and BTC levels before therapy might be the predictive biomarkers of efficacy. [ABSTRACT FROM AUTHOR]