Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

Prognostic Value of Alpha-Fetoprotein in Unresectable Hepatocellular Carcinoma Treated with Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

Purpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

Efficacy and safety of TACE combined with tyrosine kinase inhibitors and camrelizumab for unresectable hepatocellular carcinoma: A systematic review and meta­analysis.

Transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and camrelizumab (collectively: T-T-C) is a novel treatment strategy for unresectable hepatocellular carcinoma (HCC). The present systematic review and meta-analysis aimed to evaluate the efficacy and safety of T-T-C compared with TACE combined with TKIs only (T-T) in the treatment of patients with unresectable HCC. A systematic literature search was conducted on T-T and T-T-C using PubMed, Embase and the Cochrane Library. Data regarding the clinical outcome, including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs), were independently extracted and analyzed by two researchers using standardized protocols. In total, 7 cohort studies, including 1,798 patients (T-T-C, 838; T-T, 960), were included in the meta-analysis. The results of the present study demonstrated that the T-T-C group had significantly prolonged OS [hazard ratio (HR), 0.38; 95% confidence interval (CI), 0.29-0.50; I2=61.5%; P=0.016)] and PFS (HR, 0.37; 95% CI, 0.30-0.46; I2=44.5%; P=0.109), and showed significantly higher objective response rates [risk ratio (RR), 0.82; 95% CI, 0.69-0.96; I2=25.1%; P=0.237)] and slightly higher disease control rates without a significant difference (RR, 0.96; 95% CI, 0.89-1.03; I2=0.0%; P=0.969). In addition, grade 3/4 AEs were more common in the T-T group, including hypertension (RR, 1.15; 95% CI, 0.85-1.56), vomiting or nausea (RR, 0.88; 95% CI, 0.44-1.76) and pain (RR, 0.74; 95% CI, 0.45-1.21); however, these results were not statistically significant. In conclusion, compared with T-T combination therapy, T-T-C demonstrated a notable advantage in terms of OS, PFS, ORR and DCR in patients with unresectable HCC. For manageable AEs, although the results were not statistically significant, the incidence of AEs in the T-T group was higher than that in the T-T-C group in terms of event probability.

Neoadjuvant therapy of sequential TACE, camrelizumab, and apatinib for single huge hepatocellular carcinoma (NEO-START): study protocol for a randomized controlled trial.

BACKGROUND: The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. METHODS: This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. DISCUSSION: Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. TRIAL REGISTRATION: www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

Early salvage therapy with anti-PD-1 antibody Camrelizumab in patients with advanced cervical cancer: a retrospective study.

OBJECTIVE: To observe the clinical efficacy of Camrelizumab in patients with advanced cervical cancer who presented with resistance to initial therapy. METHODS: We retrieved data from 25 patients with advanced (stage IIA2-IV) cervical cancer who were administered a combination salvage therapy with Camrelizumab due to the poor response to initial chemotherapy. The primary outcome was objective response rate (ORR) and disease control rate (DCR), the secondary endpoints included progression-free survival (PFS) and the occurrence of adverse events. To evaluate its long-term effect on PFS, we included 64 patients diagnosed with stage IIA2-IV during the study period, who were responsive to initial radiotherapy or chemotherapy and received conventional therapy as control. RESULTS: Camrelizumab exhibits a high salvage treatment efficacy, with ORR of 80.0% (20/25) and DCR of 88.0% (22/25) in Camrelizumab salvage group (CS group). The PFS in CS group was significantly longer than that in control group. The median follow-up time were 18.1 and 18.3 months in the CS group and the control group, respectively, and neither achieved median PFS. The adverse event (AEs) rates in the CS and control groups were 52.0% (13/25) and 51.6% (33/64), in which the most common adverse events were myelosuppression, cutaneous capillary endothelial proliferation (CCEP), and elevated liver enzymes, and the grade of AEs was less than grade 3 in all patients. CONCLUSION: Camrelizumab demonstrated promising efficacy and safety as the early salvage treatment for patients with advanced cervical cancer.

Camrelizumab combined with anlotinib as second-line therapy for metastatic or recurrent small cell lung cancer: a retrospective cohort study.

Introduction: This retrospective study evaluates the efficacy of camrelizumab combined with anlotinib versus chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) undergoing second-line treatment. Methods: Data were sourced from medical records at a Chinese medical facility, involving 34 patients diagnosed with ES-SCLC after failing first-line treatment. Patients were divided into two groups: one received camrelizumab (200 mg every 3 weeks) with anlotinib (12 mg daily for 14 days followed by a 7-day rest), while the other group received physician-chosen chemotherapy administered every 3 weeks. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: The combination therapy group showed a significant improvement in PFS compared to the chemotherapy group (median PFS: 7 months vs. 3 months; hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.15-0.77; p<0.001). However, there was no statistically significant difference in OS between the groups (16.3 months vs. 17.3 months; p=0.82). The ORR was 52.9% in the combination therapy group versus 23.5% in the chemotherapy group (p=0.08), and the DCR was 82.4% compared to 58.8% (p=0.26). Grade 3 or higher adverse events were observed in 17.6% of the combination therapy group and 29.4% of the chemotherapy group. Conclusions: The findings suggest that the combination of camrelizumab and anlotinib offers a superior anti-tumor response with a manageable safety profile in a second-line setting for ES-SCLC patients. This combination regimen may be a viable option for second-line ES-SCLC treatment.

Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a PD-1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1:1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by 2 cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either 6 cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or 6 cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in experimental arm and 118 patients in control arm, with surgery performed in 92% and 83.9%, respectively. At data cutoff (July 11, 2023), the pCR rate were 39.8% (95% CI, 30.7 to 49.5) in experimental arm compared to 15.3% (95% CI, 9.3 to 23.0) in control arm (difference, 24.6%; odds ratio, 3.7; 95% CI, 2.0 to 6.9; p < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, grade ≥ 3 treatment-related adverse events were 29.2% and 27.2%. 3-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

Camrelizumab-induced anaphylactic reaction: a case report and literature review.

Camrelizumab is an immune checkpoint inhibitor clinically used to treat various types of tumours. In this study, the authors provided the first report of a case of an anaphylactic reaction induced by camrelizumab in the treatment of a patient with squamous cell carcinoma of the floor of the mouth. The patient, a 58-year-old man, was diagnosed with advanced squamous cell carcinoma of the floor of the mouth, with cancer infiltration and multiple metastases. He underwent treatment for nine cycles, in which cycles 1-5 he received camrelizumab, albumin-bound paclitaxel, and cisplatin (200 mg of camrelizumab each time, every 3 weeks), with no adverse reactions; in cycle 6, he received albumin-bound paclitaxel and cisplatin, with no adverse reactions; and in cycles 7-9, he received camrelizumab and albumin-bound paclitaxel. However, 30 min after 8th administration of camrelizumab (cycle 9), he suddenly developed sweating, a pale complexion, clamminess and cyanosis of the limbs (percutaneous arterial oxygen saturation [SpO2] = 82%, blood pressure [BP] = 79/49 mmHg, heart rate [HR] = 83 beats/min [bpm] and respiratory rate [RR) = 12 bpm). The patient underwent intravenous infusion of methylprednisolone (80 mg) combined with dopamine to boost the BP; he regained consciousness 20 min later, and many parts of his skin appeared smooth, with no desquamation and accompanied by itching erythema, especially on the upper limbs. Approximately 2 h after treatment, the patient's skin erythema subsided (vital sign monitoring results: SpO2 = 100%, BP = 122/84 mmHg, HR = 91 bpm and RR = 17 bpm); the patient did not complain about his obvious discomfort. Despite the rarity of acute anaphylactic reactions among immune-related adverse reactions, great importance should be given to anaphylactic reactions of camrelizumab due to its extensive clinical application.

TACE combined Lenvatinib plus Camrelizumab versus TACE alone in efficacy and safety for unresectable hepatocellular carcinoma: a propensity score-matching study.

BACKGROUNDS: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . METHODS: A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. RESULTS: After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. CONCLUSION: TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Comparison of the efficacy and safety of domestically produced tislelizumab, camrelizumab, and imported pembrolizumab in the treatment of advanced NSCLC: a real-world retrospective study.

BACKGROUND: Since the imported PD-1 inhibitor pembrolizumab was listed in China in 2018, China has opened up the era of immunotherapy for malignant tumors, with several domestically produced PD-1 inhibitors coming onto the market one after another. To find out whether there are differences in the efficacy and safety of domestic and imported PD-1 inhibitors in patients with advanced non-small cell lung cancer, we conducted this retrospective study in two tertiary hospitals in China. METHODS: Patients with advanced NSCLC treated with tislelizumab or camrelizumab or pembrolizumab who met the inclusion criteria were screened through the electronic medical record system. A total of 259 patients were screened, but due to the unbalanced baseline, we performed propensity score matching and finally included 149 patients in three groups: pembrolizumab (n = 38), tislelizumab (n = 38), and camrelizumab (n = 73), which had very balanced baseline characteristics in each group after propensity score matching treatment. RESULTS: The results showed that the median progression-free period was 11.3 m vs 10.1 m vs 8.9 m; p = 0.754; and the objective response rate was 63.2% vs 50% vs 57.5%; P = 0.510 for pembrolizumab, tislelizumab, and carrelizumab, respectively. There was no significant difference in median PFS between PD-L1 expression subgroups. In terms of safety, only skin toxicity of any grade of carrelizumab was higher than that of the other two groups (p = 0.034), and the incidence of grade ≥ 3 adverse reactions was not statistically significant among the three groups. CONCLUSION: In this real-world study, the efficacy and safety of the domestically produced tislelizumab, camrelizumab, and the imported pembrolizumab were comparable.

Sorafenib plus transcatheter arterial chemoembolization with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma.

OBJECTIVES: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analysed 78 patients with intermediate or advanced HCC who were treated at our centres between January 2018 and December 2021. Twenty-six of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. RESULTS: The median OS (22 vs 10 months, P < .001) and median PFS (11 vs 6 months, P = .008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumour progression. For grade I and II AEs, the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the 2 groups (P > .05). CONCLUSION: Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. ADVANCES IN KNOWLEDGE: (1) Subgroup analysis demonstrated that TACE + sorafenib + camrelizumab could benefit HCC patients regardless of whether they had portal vein tumour thrombosis, Barcelona Clinic Liver Cancer B or C, or CHILD A or B; (2) We reported the immunotherapy-related AEs occurred with a significantly higher incidence in triple treatment, but all the AEs are tolerable.

Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study.

BACKGROUND: The combination of immune checkpoint inhibitors and antiangiogenic agents has been effective in treating multiple cancers. This was further explored in an open-label, multicenter phase 2 basket study (NCT04346381), which evaluated the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients with advanced solid tumors. We herein report the findings from the cohort of advanced NSCLC patients who progressed after treatment with platinum-doublet chemotherapy and immunotherapy. METHODS: Eligible patients were enrolled and treated with camrelizumab (200 mg once every 3 weeks via intravenous infusion) and oral famitinib (20 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled in this cohort, with a median follow-up duration of 11.5 months. Three patients (7.5%) achieved a partial response, and 29 patients (72.5%) achieved stable disease. The ORR and DCR with this combination regimen were 7.5% (95% CI, 1.6-20.4) and 80.0% (95% CI, 64.4-90.9), respectively. The median DoR was 12.1 months (95% CI, 10.3-not reached). The median PFS was 5.4 months (95% CI, 4.1-7.5), and the median OS was 12.1 months (95% CI, 9.1-16.7). The estimated 12-month OS rate was 51.5% (95% CI, 34.9-65.9). The most frequent grade 3 or higher treatment-related adverse events occurring in more than 5% of patients included hypertension (27.5%), palmar-plantar erythrodysesthesia syndrome (10%), decreased neutrophil count (10%), and proteinuria (7.5%). CONCLUSION: Camrelizumab plus famitinib demonstrated favorable benefits in PFS and OS, along with manageable safety profiles, in patients with advanced NSCLC who progressed after platinum-doublet chemotherapy and immunotherapy. This finding warrants further exploration.

Hepatic artery infusion chemotherapy combined with camrelizumab plus rivoceranib for hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter propensity score-matching analysis.

BACKGROUND: Portal vein tumor thrombosis (PVTT) signifies late-stage hepatocellular carcinoma (HCC) with high-risk progression and poor prognosis. As a standard treatment, sorafenib monotherapy has limited the efficacy in managing HCC with PVTT. Currently, both hepatic arterial infusion chemotherapy (HAIC) and the combination of camrelizumab and rivoceranib have shown favorable survival benefits for advanced HCC, surpassing the standard sorafenib treatment. In this study, we investigate the safety and efficacy of HAIC combined with camrelizumab and rivoceranib in treating HCC patients with PVTT. METHODS: From January 2020 to December 2021, HCC patients with PVTT, who received either a triple regime of HAIC combined with camrelizumab and rivoceranib or a dual regime of camrelizumab and rivoceranib as their first-line treatment, were reviewed for eligibility at four hospital centers in China. To balance any intergroup differences, propensity score matching (PSM) was applied. The aim of this study is to compare the efficacy of the dual and triple combination treatment regimens based on survival prognosis and tumor response and evaluate the safety based on the occurrence of adverse reactions. RESULT: In this study, a total of 411 patients who received either the triple treatment regime (HAIC combined with camrelizumab plus rivoceranib, referred to as the HAICCR group, n = 292) or the dual treatment regime (camrelizumab combined with rivoceranib, referred to as the CR group, n = 119) between January 2020 and December 2021 were included. The results showed that the HAICCR group exhibited significantly better overall survival (mOS: 19.60 months vs. 11.50 months, p < 0.0001) and progression-free survival (mPFS: 10.0 months vs. 5.6 months, p < 0.0001) compared to the CR group in the overall cohort. Moreover, the HAICCR group also had a significantly higher ORR (objective response rate, 55.5% vs. 42.0%, p = 0.013) and DCR (disease control rate, 89.0% vs. 79.0%) compared to the CR group. After PSM, a final matched cohort of 83 pairs was obtained, and the survival benefits were consistent in this cohort as well (mOS: 18.70 months vs. 11.0 months, p < 0.0001; mPFS: 10.0 months vs. 5.6 months, p < 0.0001). However, there was no significant difference in the ORR between the triple and dual combination regimes. Univariate and multivariate analysis showed that CTP (Child-Turcotte-Pugh) stage, ALBI (albumin-bilirubin index) grade, tumor number, and treatment regime were significant risk factors affecting overall survival, while AFP (α-fetoprotein) level, tumor number, metastasis, and treatment regime were significant risk factors affecting progression-free survival. As for safety, hypertension and hand-foot syndrome were the two most common adverse reactions in both groups, with no significant difference in the occurrence of adverse reactions between the two groups (p < 0.05). CONCLUSION: In the context of advanced HCC patients with PVTT, the combination regime of HAIC and camrelizumab plus rivoceranib demonstrates more excellent capacity for prolonging survival and offers a well-tolerated safety compared to the CR dual therapy approach. This triple regime represents a therapeutic modality of broad prospects and vast potential for HCC patients with PVTT.

Cost-effectiveness analysis of tislelizumab vs. camrelizumab for the treatment of second-line locally advanced or metastatic esophageal squamous cell carcinoma.

BACKGROUND: Esophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China. METHODS: From the perspective of China's healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results. RESULTS: Compared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1-3 times GDP per capita in China($11,207/QALY∼$33,621/QALY). Scenario analysis showed that the result was consistent. CONCLUSION: Tislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.

Immune checkpoint inhibitors as the second-line treatment for advanced esophageal squamous cell carcinoma: a cost-effectiveness analysis based on network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.

Primary Pulmonary Lymphoepithelioma-like Carcinoma: A Case Report Utilizing Camrelizumab and Anlotinib for Prolonged Survival.

BACKGROUND: Primary Pulmonary Lymphoepithelioma-like Carcinoma (PPLELC) is a rare form of cancer for which no standard treatment has been established to date. Patients with advanced-stage PPLELC generally have a poor prognosis with overall survival of 22.7 months. CASE PRESENTATION: Here, we report a case of advanced primary pulmonary lymphoepithelioma-like carcinoma. Initially, the patient underwent a first-line (GP) and a second-line (DP) of chemotherapy, which provided temporary relief but resulted in varying degrees of myelosuppression. When the disease progressed again, we administered a third-line treatment consisting of camrelizumab combined with anlotinib. RESULT: This resulted in a progression-free survival of over 26 months without significant toxic side effects. CONCLUSION: Our findings suggest that combining camrelizumab and anlotinib could lead to a long progressionfree survival in patients with advanced PPLELC.

Long survival after neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery in a patient with hepatoid adenocarcinoma of the lung: A case report.

Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of lung cancer. The prognosis for patients with HAL is generally poor and currently, there are only limited treatment options. Here, we present a case of a 47-year-old male diagnosed with locally advanced-stage HAL who achieved a remarkably long disease-free survival after receiving neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery. This case highlights the potential of immunochemotherapy plus surgery in improving outcomes for patients with HAL.

Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab.

Background: Camrelizumab, a programmed death 1 (PD-1) inhibiting antibody, has demonstrated efficacy in various malignancies and received approval in multiple countries. Despite its therapeutic benefits, camrelizumab is associated with a unique spectrum of immune-related adverse effects (irAEs), predominantly reactive cutaneous capillary endothelial proliferation (RCCEP). However, visceral manifestations of such endothelial proliferations, particularly hepatic cavernous hemangiomas, have not been extensively documented. Methods: This case series retrospectively reviews six patients who developed hepatic hemangiomas following treatment with camrelizumab in combination with other chemotherapeutic agents. The series highlights the clinical course, imaging findings, management strategies, and outcomes associated with this complication. A detailed analysis was conducted to discern the potential causal relationship between camrelizumab therapy and the development of hepatic hemangiomas. Results: All six patients, after varying cycles of camrelizumab-based therapy, presented with hepatic lesions identified as cavernous hemangiomas on imaging. These findings were atypical for metastatic disease and were further complicated by significant clinical events, including massive intra-abdominal bleeding post-biopsy. Discontinuation of camrelizumab led to a reduction in the size of the hemangiomas in two cases, suggesting a potential link between the drug and the development of these vascular lesions. The incidence of RCCEP remained high, and the use of other agents such as bevacizumab did not mitigate the occurrence of hepatic hemangiomas, indicating a possible unique pathogenic mechanism associated with camrelizumab. Conclusion: Hepatic cavernous hemangioma may represent a rare but clinically significant irAE associated with camrelizumab therapy. This series underscores the importance of vigilant monitoring and a high index of suspicion for atypical hepatic lesions in patients undergoing treatment with PD-1 inhibitors. Further studies are warranted to elucidate the pathophysiology of this complication and to establish guidelines for the management and surveillance of patients receiving camrelizumab.

A Correlation Evaluation Between the Peripheral Blood Index and the Prognosis of Advanced Esophageal Squamous Cell Carcinoma Patients Treated with Camrelizumab.

Purpose: This study aimed to investigate the relationship between peripheral blood indices and the efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) patients treated with camrelizumab. Patients and Methods: We retrospectively analyzed 64 patients who received camrelizumab for advanced ESCC at the Second People's Hospital of Lianyungang City between July 2020 and June 2022. The study included examination of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic inflammation index (SII), the lymph-to-monocytes ratio (LMR), the absolute lymphocyte count (ALC), and lactate dehydrogenase (LDH). We used multivariate logistic regression analysis to explore the link existing between peripheral blood and the efficacy of treatment. Determination of potential prognostic factors for Progression-free survival (PFS) and Overall survival (OS) using Cox regression analysis. The nomogram model was developed based on the results of the Cox multivariate analysis. Patients were divided into three groups according to the reduction in LDH and LDL levels before treatment, and the Kaplan-Meier survival curves for the three groups were compared and ROC curves for LDH combined with PLR were plotted. Results: Lower LDH (OR=6.237, 95% CI: 1.625-23.944) were independently associated with disease control rates(DCR). LDH was independently correlated with PFS (HR: 0.227 95% CI: 0.099-0.517). LDH and PLR were independently linked to OS. The C index of the nomogram model is 0.819, indicating good predictive performance. Kaplan-Meier Survival Curve suggested better OS in patients with reduced pretreatment LDH and PLR. The area under the ROC curve showed that the LDH index combined with the PLR index predicts patient survival better than the index alone. Conclusion: LDH combined with PLR predicted prognosis in patients with ESCC treated with camrelizumab.