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Background: Regional lymph nodes that are fixed and fused into clusters or those exhibiting metastases outside the regional lymph nodes are generally classified as stage IV (M1) or unresectable. Patients with such nodes almost always need pre-operative treatment so that they can undergo surgical resection. Combining immunotherapy with trastuzumab and chemotherapy significantly improved the prognosis of HER-2 positive gastric/gastroesophageal junction (G/GEJ) cancer. However, very few reports are available on the role of immunotherapy in converting patients with unresectable cancer to resectable cancer. Methods: In this study, we report on four patients with GC who were preoperatively treated with a combination of sintilimab, trastuzumab, and chemotherapy at Hubei Cancer Hospital, China, from January 2022 to October 2023. Both preoperative and postoperative clinical and pathological characteristics of each patient were analyzed. The preoperative tumor stage was cT4N3M1. Results: Postoperative pathological results showed that two patients achieved pathological complete remission (pCR), while the pathological stage in the other two patients decreased to ypT1N0M0 and ypT2N0M0. None of them had nerve or vascular invasion. None of the patients had recurrences or metastases until the last follow-up (October 2024) after primary surgery. The present case report suggests that a combination of immunotherapy comprising trastuzumab and chemotherapy can improve the efficiency of conversion therapy for patients with HER-2 positive locally advanced G/GEJ cancer. This study also demonstrates the safety of immune checkpoint inhibitors in a conversional treatment approach. Conclusion: We showed that a pathological complete response (pCR) can be obtained even with unresectable advanced GC through treatment with sintilimab combined with neoadjuvant chemotherapy and trastuzumab. [ABSTRACT FROM AUTHOR]

Tail effect is a unique phenomenon in immunotherapy characterized by the prolonged maintenance of therapeutic efficacy. It can be observable even after treatment cessation. Immunotherapy has gradually become a vital regimen for the treatment of advanced lung cancer patients, among which immune-combined therapies based on immune checkpoint inhibitors (ICIs) have been applied clinically and demonstrates considerable clinical efficacy. In this case report, the patient was pathologically diagnosed with pulmonary sarcomatoid carcinoma (PSC), a rare and highly aggressive subtype of non-small cell lung cancer (NSCLC) known for its poor prognosis due to high invasiveness and metastatic potential. After developing resistance to chemotherapy, the patient was treated with a combined regimen of sintilimab and anlotinib, leading to initial clinical improvement. Following just three cycles of this regimen, treatment was discontinued, and the patient was discharged. Remarkably, over the subsequent months, the patient exhibited a significant tail effect, evidenced by sustained therapeutic stability, continuous tumor regression, stable low levels of serum carcinoembryonic antigen (CEA), and further improvement in clinical symptoms. Tail effect is a golden tail of immunotherapy. This case illustrates that the tail effect of immunotherapy can offer substantial survival benefits for patients with unresectable advanced lung cancer who have failed chemotherapy. [ABSTRACT FROM AUTHOR]

This article reports on a 78-year-old male patient with advanced pulmonary sarcomatoid carcinoma with positive PD-L1 expression, who achieved partial remission (PR) and progression-free survival (PFS) of 30 months with sindilizumab and amilorotinib. Grade 2 hypertension and other transient cardiac problems occurred during treatment, but overall quality of life was good. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC) is a highly challenging subtype due to a unique tumor microenvironment. Several evidence (IMpassion130 trial and KEYNOTE-355 trial) supported the therapeutic effect of the immune checkpoint inhibitor in TNBC. However, the efficacy and safety of the PD-1 inhibitor sintilimab in breast cancer (BC) has not been well-investigated. So the real-world data on sintilimab-treated patients with metastatic BC were collected and analyzed in this study. Methods: The patients were eligible according to the requirements included: ages between 18 years and 75 years; recurrent or metastatic TNBC; measurable disease based on RECIST v1.1; no limitation on the prior systemic treatments; and ECOG performance status of 0--1. Patients received sintilimab 200 mg intravenously every 3 weeks until unacceptable toxicity or disease progression. Results: From 1 June 2019 to 1 October 2022, 40 female patients (median age, 55.5 years) with metastatic TNBC (mTNBC) were enrolled into the study. The median prior lines of systemic therapy for mTNBC was three (range, 1--8), with 60% of cases receiving at least three lines of therapy for metastatic disease. The visceral or brain metastasis was detected in 40.4% or 9.6% of patients, respectively. The median duration of response was 2.8 months (range, 0.7--21.0), and the median number of sintilimab doses administered was 4 (range, 1--30). The ORR and DCR were 22.5% and 72.5%, separately. The median PFS was 3.5 months (range, 1.4--21.0), with a 6-month PFS rate of 15.0% (6/40). The median OS was 52.5 months (range, 9.0--247.0) as of data cut-off. Common adverse effects were acceptable, and fatigue, skin rash, and pruritus were the frequent toxicity observed. Two cases of grade 3 curable adverse events were considered to be treatment-related. PD-L1-positive tumor was found in 40% cases (4/10) of mTNBC. Although statistical difference was not reached, the trend was obvious. Patients with PD-L1- positive tumor gained better treatment response, while the TMB-high carrier received more benefits of PFS and OS. Conclusion: In our study, preliminary evidence provided the anticancer activity and acceptable adverse effects of sintilimab administered every 3 weeks to pretreated patients with mTNBC. Sintilimab showed its efficacy and safety of immunotherapy for patients with advanced TNBC. [ABSTRACT FROM AUTHOR]

Background: The integration of transarterial chemoembolization (TACE) with systemic therapy has demonstrated improved survival outcomes in patients with unresectable hepatocellular carcinoma (HCC). However, there is limited evidence evaluating the combination of TACE with the systemic regimen of anti-PD-1/L1 inhibitor plus lenvatinib. This study aims to assess the efficacy and safety of TACE combined with lenvatinib and sintilimab in unresectable HCC patients. Methods: Unresectable HCC patients who received TACE in combination with sintilimab plus Lenvatinib as first-line treatment from 1 January 2020 to 31 March 2023 were included for the analysis. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were evaluated by modified Response Evaluation Criteria in Solid Tumors criteria. Exploratory biomarker analysis was conducted. Results: The study included 70 patients with unresectable HCC, predominantly male and infected with Hepatitis B. The median follow-up duration for the whole cohort was 13.8 months (95% CI 11.08–16.7). The ORR was 61.4% (95% CI, 49.0%–72.8%) and the DCR was 68.6% (95%CI, 56.4%–79.2%). The median PFS was 13.2 months (95% CI 11.0-NA), with a corresponding 1-year PFS rate of 50.3% (95% CI 39.7%-65.5%). The median OS was not reached, and the 1-year OS rate was 89.3% (95% CI 81.4%–97.9%). The most common treatment-related adverse events (TRAEs) were fatigue 38.6% (27/70), hypertension 32.9% (23/70), and hand-foot syndrome 31.4% (22/70). Most TRAEs were mild-to-moderate and manageable. In addition, significant predictive value was found in alpha-fetoprotein levels (AFP), with patients showing a level of decrease post-treatment having better PFS. Conclusion: The combination regimen demonstrated promising efficacy in treating unresectable HCC, accompanied by manageable safety profiles. Furthermore, the results of this investigation suggest that AFP holds promise as predictive biomarkers for this treatment strategy. [ABSTRACT FROM AUTHOR]

Abstract Background The combination of targeted therapy and immunotherapy has improved the clinical outcomes of unresectable hepatocellular Carcinoma (HCC). However, the overall prognosis remains suboptimal. This study aims to evaluate the efficacy and safety of a novel combination of radiofrequency ablation (RFA) with lenvatinib plus sintilimab in unresectable HCC. Methods In this retrospective study, patients diagnosed with unresectable HCC were included and divided into two cohorts: RFA combined with lenvatinib plus sintilimab (R-L-S group) and lenvatinib plus sintilimab (L-S group). The primary efficacy endpoints were objective response rate (ORR) and progression free survival (PFS). Adverse events were analyzed to assess the safety profiles. Results The median follow-up periods for the entire cohort were 14.0 months. The R-L-S group (n = 60) had a significantly higher ORR than those with L-S alone (n = 62) (40.0% vs. 20.9%; p = 0.022). Moreover, patients in the R-L-S group had improved median PFS (12 vs. 8 months; p = 0.013) and median overall survival (24 vs. 18 months; p = 0.037), as compared with lenvatinib and sintilimab alone. No significant difference in treatment related adverse event (TRAE) of any grade between the two groups. The most common TRAEs of grade ≥ 3 were fatigue 10.0% (6/60) and hand-foot skin reaction 10.0% (6/60) in the R-L-S group and hand-foot skin reaction 11.3% (7/62) in the L-S group. Conclusion In unresectable HCC patients, the incorporation of RFA to lenvatinib plus sintilimab demonstrated improved efficacy without compromising safety compared with lenvatinib plus sintilimab alone.

Huichun Yang, Zhengwen Chen, Hongyan Lou, Weijia Ying, Zeying Chai Department of Gynecology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, 317016, People’s Republic of ChinaCorrespondence: Zeying Chai, Department of Gynecology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, 317016, People’s Republic of China, Tel +86-013634092882, Email chaizythwmu@tsu-edu.cnPurpose: We aimed to evaluate the effects of sintilimab plus radiotherapy on levels of Spondin-2 and glucose transporter-1 (Glut-1) in patients with cervical cancer.Patients and Methods: A total of 112 patients with cervical cancer treated from January 2019 to January 2021 were selected in this randomized control trial and divided into a control group (n = 56) and a study group (n = 56) using the random number table method. Chemotherapy using docetaxel + cisplatin was performed for both groups, based on which the control group was given radiotherapy (external conformal radiotherapy + intracavitary irradiation), and the study group received sintilimab plus radiotherapy. The treatment lasted for six cycles, with 21 days as one cycle.Results: The total response rate of the study group was higher than that of the control group (55.36% vs 33.93%) (P < 0.05). There were no significant differences in adverse effects between the two groups (P > 0.05). After six cycles of treatment, the levels of carcinoembryonic antigen, squamous cell carcinoma antigen, vascular endothelial growth factor-A, vascular endothelial growth factor receptor 2, Spondin-2 and Glut-1 decreased in both groups compared with those before treatment, and they were lower in the study group (P < 0.05). The survival rate of the study group was higher than that of the control group (87.50% vs 71.43%) (P < 0.05).Conclusion: Sintilimab plus radiotherapy can effectively reduce the levels of serum tumor markers, such as Spondin-2 and Glut-1, and enhance the clinical efficacy on patients with cervical cancer, without increasing adverse effects.Keywords: cervical cancer, glucose transporter-1, radiotherapy, sintilimab, spondin-2

Abstract Background Antiangiogenic treatment and immunochemotherapy effectively treat patients with advanced esophageal cancer. However, there remains a dearth of studies concerning neoadjuvant therapy for resectable esophageal cancer. Methods The study focused on patients with T2–4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for antiangiogenesis and sintilimab (200 mg) and chemotherapy for three cycles. Surgical treatment was performed 4–6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) and safety. Results Out of the 34 screened patients, 17 were successfully enrolled in the study, and 14 completed the entire treatment process. The pCR was 35.3% (6/17). However, two patients experienced mortality. The occurring rate of grade 3 or higher complications after the surgery was 78.6% (11/14) according to Clavien–Dindo classification. Specifically, anastomotic leakage was observed in 57.1% (8/14) of the patients. Conclusion Compared to neoadjuvant chemotherapy, the current regimen demonstrated improved pCR. However, it did not show significant improvement compared to immunochemotherapy. It is essential to exercise caution when using this treatment approach in patients with esophageal cancer as it might increase postoperative complications, especially anastomotic leakage.

Background: Immune checkpoint inhibitors (ICIs) have become a prevalent tool in anti-tumor therapy in recent years. They may cause immune-related adverse events (irAEs) including potentially life-threatening cardiovascular toxicities such as myocarditis. Case presentation: In this report, we describe a 69-year-old man with recurrent esophageal cancer who developed myocarditis after receiving three cycles of sintilimab combined with nab-paclitaxel. Despite a rising cardiac troponin I (cTnI), he initially reported no discomfort. He was later suspected of having with sintilimab-induced myocarditis. Although treatment with methylprednisolone reduced his cTnI levels, he still experienced significant discomfort. Moreover, he developed pneumonia and septic shock. Conclusion: In our literature search to identify all reported cases of sintilimabassociated adverse events involving myocarditis, we found 14 patients, including those with esophageal cancer, thymoma, lung cancer, gastric cancer, hepatobiliary carcinoma, and chordoma. The primary treatment for ICIinduced cardiotoxicity is methylprednisolone. However, the long-term or highdose use of steroids can also induce side effects, which have not been the focus of these case reports. This is the first reported case of asymptomatic immunemediated myocarditis occurring during the treatment of esophageal cancer with sintilimab. It is also the first to address the side effects of methylprednisolone used in the treatment of sintilimab-related myocarditis. To facilitate an early diagnosis, regular monitoring is required during sintilimab treatment. We should also focus on the prevention and management of adverse effects related to steroid use. [ABSTRACT FROM AUTHOR]

Background: The Chinese Society of Clinical Oncology (CSCO) has recommended sintilimab plus chemotherapy (SINT + Chemo) as a standard first-line therapy for advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC), based on the proven effectiveness and safety in the ORINT-16 trail. Its cost-effectiveness, however, remains to be evaluated. Methods: We established a partitioned survival approach (PartSA) model with a 10-year time horizon to determine whether SINT + Chemo (vs. chemotherapy) was more cost-effective as a first-line treatment for unresectable advanced or metastatic GC/GEJC. Survival data was generated from the ORIENT-16 trail. Cost calculation was limited to direct medical costs. Database of Hunan Public Resources Trading Service Platform was used as the source for obtaining drug prices. Other cost and utility values were gathered from established literature. Incremental cost-effectiveness ratio (ICER) was the primary output. Additionally, we conducted sensitivity analysis, subgroup analysis, and scenario analysis. Results: In the base-case analysis, group SINT + Chemo showed an increase in utility value by 0.32 quality-adjusted life-years (QALYs) at an extra cost of $7988.43, resulting in an ICER of $25239.29/QALY, below the Chinese cost-effective willingness-to-pay (WTP) threshold of $38223.34. Upon further subgroup analysis according to patients' programmed death 1 ligand (PD-L1) combined positive score (CPS), the ICERs were $26341.01/QALY for patients highly expressing PD-L1 (CPS ≥5) and $17658.26/QALY for patients lowly expressing PD-L1 (CPS <5). Based on the sensitivity analysis, we found the PFS utility was the parameter that had the most significant impact on the model's outcomes. Moreover, in scenario analysis, the results remained consistent despite variations in the model's time frame. Conclusion: In China, SINT + Chemo is a more cost-effective option (vs. chemotherapy) as a first-line therapy for unresectable advanced or metastatic GC/GEJC, irrespective of PD-L1 expression levels. [ABSTRACT FROM AUTHOR]

Background: The treatment of unresectable hepatocellular carcinoma (uHCC) challenging due to unfulfilled clinical requirements. Objective: To evaluate the safety and efficacy of combining transarterial chemoembolization (TACE) with sintilimab and lenvatinib in the treatment of uHCC. Methods: We retrospectively analyzed the data of patients with uHCC who were treated with a combination of TACE, sintilimab, and lenvatinib between May 2019 and December 2021 at the Chinese PLA General Hospital. Systemic treatment was started 1 week after TACE was performed. Sintilimab was administered intravenously at a dosage of 200 mg every three weeks, and lenvatinib was given orally at dosages of 8 mg or 12 mg daily, contingent upon the weight of the patients. The primary endpoint was the objective response rate (ORR) as per the mRECIST. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (tr-AEs). Results: A total of 32 patients were enrolled in the study. Among them, 9 patients were classified as Barcelona Clinic Liver Cancer-B (BCLC-B), 23 patients were classified as BCLC-C, 14 patients diagnosed with portal vein tumors, and 12 patients were diagnosed with extra hepatic metastases. The ORR and DCR were 75% and 90.6% respectively, with 4 patients exhibiting (12.5%) complete response, 20 patients exhibiting (62.5%) partial response, 5 patients exhibiting (15.6%) stable disease, and 3 patients exhibiting (9.4%) progressive disease. With a median follow-up time of 19.6 months, the median PFS was 9.9 months, and the median OS was 33.3 months. A total of 31 patients experienced different degrees of tr-AEs, of which 2 were grade 3 tr-AEs. Conclusion: The combination therapy of TACE, sintilimab, and lenvatinib demonstrates satisfactory efficacy in the treatment of uHCC with manageable tr-AEs. [ABSTRACT FROM AUTHOR]

Purpose: The retrospective study was to explore the effectiveness and safety of GemOx (gemcitabine, oxaliplatin) plus sintilimab (belongs to the class of drugs known as immune checkpoint inhibitors, particularly targeting the PD-1 receptor) in relapse or refractory nodal PTCLs. Methods: Patients with nodal PTCL who initiated salvage therapy with sintilimab and GemOx between January 2020 to September 2021 were identified from the database of the hematology department of the Second Affiliated Hospital of Zhejiang University School of Medicine. All patients received 2–4 cycles (3 weeks/cycle) of treatment of sintilimab (200 mg, I.V, D1) in combination with GemOx. Treatment response was assessed every six weeks during the salvage treatment phase. Eligible patients received maintenance therapy according to the investigator’s decision. Follow-ups were routinely conducted every three months. Results: 31 patients with r/r nodal PTCLs were enrolled, including 23 PTCL-NOS, 4 AITL, and 4 ALCL. 21 (67.7%) patients received at least two lines of therapy. 71.0% (95% CI, 53.4%-83.9%) of patients documented objective response of 2–4 cycles of sintilimab plus GemOx therapy, including 9 complete response and 13 partial response. 21 (67.7%) patients received consolidation therapy, including 5 autologous stem-cell transplantation and 12 histone deacetylase inhibitors. After a median 25.6 months follow-up, the median PFS was 22.0 (95% CI,11.8–24.7) months, and the median OS was 26.2 (95% CI, 24.4 –NA) months. 29 (93.5%) patients experienced at least one adverse event, and 26 (83.9% patients only had mild (grade 1–2) AEs.Univariable Cox regression showed the progression risk of AITL is 22.7 (3.9- 131.0, p < 0.01) times of PTCL-NOS, while the HR of ALCL was 1.14 (0.33–3.96,p = 0.833). Conclusion: Sintilimab plus GemOx showed encouraging activity and manageable toxicity for patients with r/r PTCL. [ABSTRACT FROM AUTHOR]

Background: Adrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC. Case presentation: We report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm × 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient’s lung metastases and the left adrenal gland area mass (39mm × 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism. Conclusion: This case highlights the remarkable response of our patient’s ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma. [ABSTRACT FROM AUTHOR]

Background: The combination of targeted therapy and immunotherapy has improved the clinical outcomes of unresectable hepatocellular Carcinoma (HCC). However, the overall prognosis remains suboptimal. This study aims to evaluate the efficacy and safety of a novel combination of radiofrequency ablation (RFA) with lenvatinib plus sintilimab in unresectable HCC. Methods: In this retrospective study, patients diagnosed with unresectable HCC were included and divided into two cohorts: RFA combined with lenvatinib plus sintilimab (R-L-S group) and lenvatinib plus sintilimab (L-S group). The primary efficacy endpoints were objective response rate (ORR) and progression free survival (PFS). Adverse events were analyzed to assess the safety profiles. Results: The median follow-up periods for the entire cohort were 14.0 months. The R-L-S group (n = 60) had a significantly higher ORR than those with L-S alone (n = 62) (40.0% vs. 20.9%; p = 0.022). Moreover, patients in the R-L-S group had improved median PFS (12 vs. 8 months; p = 0.013) and median overall survival (24 vs. 18 months; p = 0.037), as compared with lenvatinib and sintilimab alone. No significant difference in treatment related adverse event (TRAE) of any grade between the two groups. The most common TRAEs of grade ≥ 3 were fatigue 10.0% (6/60) and hand-foot skin reaction 10.0% (6/60) in the R-L-S group and hand-foot skin reaction 11.3% (7/62) in the L-S group. Conclusion: In unresectable HCC patients, the incorporation of RFA to lenvatinib plus sintilimab demonstrated improved efficacy without compromising safety compared with lenvatinib plus sintilimab alone. [ABSTRACT FROM AUTHOR]

In a variety of cancers, immune checkpoint inhibitors (ICIs) have demonstrated substantial survival advantages. Nevertheless, the widespread use of ICIs in the clinic has resulted in a growing interest in immune-related adverse events (irAEs) and their treatment methods. This paper reports a case in which a patient with three sequential severe irAEs was successfully treated. After undergoing two regimens of sintilimab in conjunction with chemotherapy for advanced lung cancer, the patient developed myocarditis combined with hepatitis. Subsequently, the patient developed pneumonia following remission from treatment. We also discuss the mechanism of irAEs, principles of treatment, and progress in the study of biomarkers for early prediction of irAEs by reviewing the literature. [ABSTRACT FROM AUTHOR]

Thymic carcinoma (TC) is an uncommon type of thymic epithelial tumors. Patients with relapsed or refractory TCs have a poor prognosis. Immune checkpoint inhibitor monotherapy can be applied as a second-line treatment for such cases. This study reported a TC patient who did not respond to conventional chemotherapy and radiotherapy but achieved prolonged partial remission lasting 17 months following the third-line treatment with antiprogrammed cell death-1 inhibitor sintilimab. This patient did not experience any serious side effects associated with sintilimab treatment. The above results demonstrated that sintilimab could be a feasible therapeutic option for refractory TC patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy and safety of sintilimab injection combined with paclitaxel injection (albumin-bound) in the second-line treatment of patients with relapsed or refractory extensive stage (ES) of small cell lung cancer (SCLC). METHODS: A total of 74 patients with ES-SCLC who progressed after first-line application of etoposide / platinum-based chemotherapy admitted into Beijing Friendship Hospital, Capital Medical University from Jan. 2022 to Jan. 2023 were selected to be divided into 38 cases in the research group and 36 cases in the control group via random number table method. The research group was given sintilimab injection combined with paclitaxel injection (albumin-bound), while the control group received topotecan hydrochloride injection. The objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse drug reactions of both groups were observed. RESULTS: The ORR of research group and control group were 26. 3% (10 / 38) and 13. 9% (5 / 36) (P = 0. 035), the DCR were 84. 2% (32 / 38) and 72. 2% (26 / 36) (P = 0. 042), the median PFS were 6. 00 months and 3. 45 months (P = 0. 013), the median OS were 10. 30 months and 8. 75 months (P = 0. 007), respectively, with statistically significant differences. There was no statistically significant difference in the incidences of adverse drug reactions between two groups (P>0. 05). CONCLUSIONS: Compared with the topotecan hydrochloride injection, sindilizumab injection in combination with paclitaxel (albumin-bound) has prolonged survivals in patients with relapsed or refractory ES-SCLC with tolerable adverse drug reactions. [ABSTRACT FROM AUTHOR]

Background: As one of the most common types of primary bone sarcomas in adolescents and young adults, osteosarcoma has a high probability of local invasion and distant metastasis with a poor prognosis. Case Presentation: Here, we report the case of a 34-year-old patient with advanced metastatic osteosarcoma. Considering the high expression of PD-L1 and the inability of the patient to tolerate chemotherapy, anti-PD-1 antibody (sintilimab 200 mg, q3w) and anti-angiogenesis drug (anlotinib 8 mg D1-14, q3w) were administered. The metastatic lesions were treated with local radiotherapy. The patient obtained an 11.7-month-sustained remission period, and he also enjoyed a better quality of life. Conclusion: This case demonstrates that sintilimab plus anlotinib may be a feasible treatment regimen for osteosarcoma patients. [ABSTRACT FROM AUTHOR]

Objective: Both camrelizumab plus paclitaxel and carboplatin (CTC) and sintilimab plus gemcitabine and cisplatin or carboplatin (SGP) have been approved by the National Medical Products Administration of China (NMPA) for the first-line treatment of local advanced or metastatic sqNSCLC. However, the comparison of the two treatments as first-line treatments in efficacy or pharmacoeconomics has barely been studied. To deeply understand the costs and outcomes of the two treatments, this work directly compared the cost-effectiveness for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland. Methods: A network meta-analysis was first performed based on the three clinical trials, namely, CameL-Sq, ORIENT-12, and C-TONG1002, to compare the clinical benefits of the two treatments. The Weibull approximation was applied to further calculate the life expectancy of the two treatments. The partitioned survivalmodel (PSM) was next established, and one-way sensitivity analysis and probabilistic sensitivity analysis were also performed to evaluate the stability of the underlying parameter values and assumptions within the model. Results: CTC treatment gained 0.68 QALYs and cost $14,764. SGP treatment gained 0.54 QALYs and cost $14,584. The CTC arm gained 0.14 additional QALYs and cost $179 more than the SGP arm, and the ICERs was $1,269/QALY, which was lower than one-fold GDP per capita in the Chinese mainland ($12,734 GDP per capita in 2022). In probabilistic sensitivity analysis, when the WTP ranged from $12,734-38,202 (1-3 folds, 2022 GDP per capita in China), the CTC group had higher probabilities than the SGP group for being cost effective, which ranged from 85.65% to 88.38%. Conclusion: From the perspective of the payers, camrelizumab plus chemotherapy was cost-effective compared with sintilimab plus chemotherapy for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland. [ABSTRACT FROM AUTHOR]

Background: Antiangiogenic treatment and immunochemotherapy effectively treat patients with advanced esophageal cancer. However, there remains a dearth of studies concerning neoadjuvant therapy for resectable esophageal cancer. Methods: The study focused on patients with T2–4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for antiangiogenesis and sintilimab (200 mg) and chemotherapy for three cycles. Surgical treatment was performed 4–6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) and safety. Results: Out of the 34 screened patients, 17 were successfully enrolled in the study, and 14 completed the entire treatment process. The pCR was 35.3% (6/17). However, two patients experienced mortality. The occurring rate of grade 3 or higher complications after the surgery was 78.6% (11/14) according to Clavien–Dindo classification. Specifically, anastomotic leakage was observed in 57.1% (8/14) of the patients. Conclusion: Compared to neoadjuvant chemotherapy, the current regimen demonstrated improved pCR. However, it did not show significant improvement compared to immunochemotherapy. It is essential to exercise caution when using this treatment approach in patients with esophageal cancer as it might increase postoperative complications, especially anastomotic leakage. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) demonstrate unique advantages in the treatment of lung cancer and are widely used in the era of immunotherapy. However, ICIs can cause adverse reactions. Hematological toxicities induced by immunotherapy are relatively rare. Agranulocytosis, a rare hematologic adverse event associated with immune checkpoint inhibitors, has received limited attention in terms of treatment and patient demographics. Herein, we report the case of a 68-year-old male with non-small cell lung cancer(NSCLC) who received two cycles of programmed cell death-1 (PD-1) antibody sintilimab immunotherapy combined with albumin-bound paclitaxel and carboplatin chemotherapy and one cycle of sintilimab monotherapy. He was diagnosed with grade 4 neutropenia and sepsis (with symptoms of fever and chills) after the first two cycles of treatment. Teicoplanin was promptly initiated as antimicrobial therapy. The patient presented with sudden high fever and developed agranulocytosis on the day of the third cycle of treatment initiation, characterized by an absolute neutrophil count of 0.0×109/L. The patient was treated with granulocyte colony-stimulating factor but did not show improvement. He was then treated with corticosteroids, and absolute neutrophil counts gradually returned to normal levels. To the best of our knowledge, this is the first reported case of sintilimab-induced agranulocytosis in a patient with NSCLC. Sintilimab-induced severe neutropenia or agranulocytosis is a rare side effect that should be distinguished from chemotherapy-induced neutropenia and treated promptly with appropriate therapies; otherwise, the condition may worsen. [ABSTRACT FROM AUTHOR]

Biliary tract cancer (BTC) is a highly aggressive malignancy with limited second‐line therapy. We conducted this phase 2 trial to evaluate the efficacy and safety of second‐line nab‐paclitaxel plus sintilimab in advanced BTC. Histologically confirmed advanced BTC patients with documented disease progression after first‐line chemotherapy were enrolled. Subjects received nab‐paclitaxel 125 mg/m2 on days 1 and 8 plus sintilimab 200 mg on day 1, administered every 3 weeks. The primary end point was the objective response rate (ORR). The secondary end points were progression‐free survival (PFS), overall survival (OS), and adverse reactions. Simultaneously, next‐generation sequencing, programmed cell death ligand 1 immunohistochemistry and multiplex immunofluorescence of tumor‐infiltrating lymphocytes were applied to explore potential biomarkers. Twenty‐six subjects were consecutively enrolled. The ORR was 26.9% (7/26), including two complete responses and five partial responses, which met the primary end point. The disease control rate was 61.5% (16/26). The median PFS was 169 days (about 5.6 months, 95% confidence interval [CI] 60–278 days). The median OS was 442 days (about 14.7 months, 95% CI 298–586 days). Grade 3 treatment‐related adverse events (TRAEs) were mainly anemia (27%), leukopenia (23%), neutropenia (19%), and peripheral sensory neuropathy (8%). No grade 4 or 5 TRAEs occurred. Biomarker analysis suggested that positive PD‐L1 and high proportions of CD8+ T‐cell infiltration were correlated with improved clinical outcome. Nab‐paclitaxel plus sintilimab is a potentially effective and tolerable second‐line regimen for advanced BTC that deserves to be studied in large‐scale trials. PD‐L1 status and CD8+ T cell infiltration might be promising biomarkers for efficacy prediction. [ABSTRACT FROM AUTHOR]

We report a case of an advanced non-small cell lung cancer (NSCLC) patient with brain metastasis, RET fusion, and high expression of programmed death ligand 1 (PD-L1) at initial treatment. After receiving radiotherapy for the brain metastasis, the patient started with anlotinib and added immunotherapy with sintilimab. The patient had a good response to anlotinib and sintilimab treatment, tolerated the adverse reactions, and had a progression-free survival (PFS) of over 17 months. To the best of our knowledge, this is the first clinical case report in the literature describing the benefit of anlotinib and sintilimab treatment for non-small cell lung cancer with RET fusion and high PD-L1 expression. This study explores the biomarker selection for targeted therapy and combined immunotherapy in NSCLC patients.

Tail effect is a unique phenomenon in immunotherapy characterized by the prolonged maintenance of therapeutic efficacy. It can be observable even after treatment cessation. Immunotherapy has gradually become a vital regimen for the treatment of advanced lung cancer patients, among which immune-combined therapies based on immune checkpoint inhibitors (ICIs) have been applied clinically and demonstrates considerable clinical efficacy. In this case report, the patient was pathologically diagnosed with pulmonary sarcomatoid carcinoma (PSC), a rare and highly aggressive subtype of non-small cell lung cancer (NSCLC) known for its poor prognosis due to high invasiveness and metastatic potential. After developing resistance to chemotherapy, the patient was treated with a combined regimen of sintilimab and anlotinib, leading to initial clinical improvement. Following just three cycles of this regimen, treatment was discontinued, and the patient was discharged. Remarkably, over the subsequent months, the patient exhibited a significant tail effect, evidenced by sustained therapeutic stability, continuous tumor regression, stable low levels of serum carcinoembryonic antigen (CEA), and further improvement in clinical symptoms. Tail effect is a golden tail of immunotherapy. This case illustrates that the tail effect of immunotherapy can offer substantial survival benefits for patients with unresectable advanced lung cancer who have failed chemotherapy.

Objective: To investigate the effects of anlotinib combined with sintilimab on serum angiogenesis factors, tumor markers, platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR) and lymphocyte/monocyte ratio (LMR) in advanced non-small cell lung cancer (NSCLC) patients. Methods: 84 advanced NSCLC patients were divided into control group (42 cases, treated with anlotinib) and study group (42 cases, treated with sintilizumab combined with anlotinib) according to the random number table method. The efficacy, serum tumor markers [cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carbohydrate antigen 125 (CA125) and carcinoembryonic antigen (CEA)], angiogenesis factors [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)], NLR, PLR, LMR were compared between two groups, the incidence of adverse reactions was observed. Results: Compared with control group post-treatment, the objective remission rate, disease control rate and LMR in study group were higher, and VEGF, bFGF, CA125, CYFRA21-1, CEA, NLR and PLR were lower (P<0.05). There was no difference in the total incidence of adverse reactions between two groups (P>0.05). Conclusion: Combined use of anlotinib and Sintilimab in the treatment of advanced NSCLC patients, which can reduce the level of tumor markers, inhibit NSCLC angiogenesis, and reduce inflammatory response. [ABSTRACT FROM AUTHOR]

Lianru Zhang,1,2,&ast; Jie Xiao,1,2,&ast; Yishan Li,1,2,&ast; Baorui Liu,1,2 Li Xie1,2 1The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Xie; Baorui Liu, The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China, Email xieli@njglyy.com; baoruiliu@nju.edu.cnPurpose: As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer.Patients and Methods: This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored.Conclusion: As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.Keywords: HDAC inhibitor, sintilimab, radiation, HER2-negative breast cancer

Abstract 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.

Juanli Fan,1 Yanmei Gong,2 Gaie Yang1 1Department of Dermatovenereology, Yuncheng Central Hospital, Shanxi Medical University, Yuncheng, Shanxi Province, 044000, People’s Republic of China; 2Department of Oncology, Yuncheng Central Hospital, Shanxi Medical University, Yuncheng, Shanxi Province, 044000, People’s Republic of ChinaCorrespondence: Juanli Fan, Department of Dermatovenereology, Yuncheng Central Hospital, Shanxi Medical University, No. 3690 Hedong East Street, Yanhu District, Yuncheng, 044000, Shanxi Province, People’s Republic of China, Tel +86 13934399917, Email fanjuanli10@126.comBackground: In contemporary times, malignancies characterized by metastatic growth have been subjected to innovative therapeutic approaches involving immunological agents known as Programmed Death Receptor 1 (PD-1) inhibitors. Notwithstanding their remarkable immunotherapeutic effectiveness, these treatments can give rise to undesirable immune-related effects. Sintilimab, a PD-1 inhibitor sanctioned for marketing by the Chinese National Medical Products Administration in 2018, has been associated with 51 reported cases of adverse reactions on the market, excluding psoriasis, up to the present moment.Case Description: Herein, we report the clinical characteristics of a patient with metastatic gastric adenocarcinoma who developed guttate psoriasis after receiving Sintilimab. The patient was an elderly male presenting with papules varying in size from that of rice grains to soybeans, accompanied by scattered erythematous lesions across his body. Notably, an atypical Auspitz’s sign was observed, wherein certain lesions were covered with a minimal amount of scale, coupled with reported persistent itching. The progression of the disease manifested within a span of one week.Conclusion: PD1 inhibitors have been associated with the recurrence, exacerbation, or new onset of psoriasis. Consequently, a personal or family history of psoriasis is an essential risk factor that needs to be considered before PD1 inhibitor medication, which helps with the early diagnosis of psoriasis. Early diagnosis of new-onset guttate psoriasis poses challenges. An early consultation with a dermatologist is recommended, and a conclusive diagnosis can be obtained through a histopathologic examination.Keywords: adverse drug reactions, PD-1 inhibitors, psoriasis, sintilimab

Background: Sintilimab plus chemotherapy has proven effective as a combination immunotherapy for patients with advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). A multi-center study conducted in China revealed a median progression-free survival (PFS) of 7.1 months. However, the prediction of response duration to this immunotherapy has not been thoroughly investigated. Additionally, the potential of baseline laboratory features in predicting PFS remains largely unexplored. Therefore, we developed an interpretable machine learning (ML) framework, iPFS-SC, aimed at predicting PFS using baseline (pre-treatment) laboratory features and providing interpretations of the predictions. Materials and methods: A cohort of 146 patients with advanced GC/GEJC, along with their baseline laboratory features, was included in the iPFS-SC framework. Through a forward feature selection process, predictive baseline features were identified, and four ML algorithms were developed to categorize PFS duration based on a threshold of 7.1 months. Furthermore, we employed explainable artificial intelligence (XAI) methodologies to elucidate the relationship between features and model predictions. Results: The findings demonstrated that LightGBM achieved an accuracy of 0.70 in predicting PFS for advanced GC/GEJC patients. Furthermore, an F1-score of 0.77 was attained for identifying patients with PFS durations shorter than 7.1 months. Through the feature selection process, we identified 11 predictive features. Additionally, our framework facilitated the discovery of relationships between laboratory features and PFS. Conclusion: A ML-based framework was developed to predict Sintilimab plus chemotherapy response duration with high accuracy. The suggested predictive features are easily accessible through routine laboratory tests. Furthermore, XAI techniques offer comprehensive explanations, both at the global and individual level, regarding PFS predictions. This framework enables patients to better understand their treatment plans, while clinicians can customize therapeutic approaches based on the explanations provided by the model. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ORIENT-16, a phase III clinical trial conducted at 62 hospitals in China, reported that add-on sintilimab (Sin) to chemotherapy (Chemo) had favorable efficacy (p < 0.05) for patients with advanced HER2-negative gastric or gastroesophageal junction cancer (GC/GEJC). This study aimed to evaluate the cost-utility of the Sin+Chemo based on results of ORIENT-16 from the perspective of Chinese healthcare payers. A three-state partitioned survival model was developed to simulate the 10-year life expectancy and total healthcare costs for patients with advanced HER2-negative GC/GEJC. Primary measure outcomes were: cost, quality-adjusted life-years (QALYs), and incremental cost-utility ratios (ICURs). Sensitivity/scenario analyses were conducted to assess the model robustness. In all patients, Sin+Chemo vs Chemo increased costs by $6,472, additionally providing 0.61 QALYs, resulting in an ICUR of $10,610/QALY. While, in PD-L1 combined positive score ≥ 5 cohort, the ICUR was $9,738/QALYs. The ICUR was most sensitive to the utility of progression-free survival. The probabilistic sensitivity analysis showed that add-on Sin had a 100% probability of being cost-effective at a willingness-to-pay threshold of $18,625/QALY gained. Sin+Chemo is a cost-effective first-line treatment option for advanced HER2-negative GC/GEJC in China. ORIENT-16, , identifier is NCT03745170. [ABSTRACT FROM AUTHOR]

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. Key points: Question: Which immune checkpoint inhibitor (ICI) is the most cost-effective for the second-line treatment of the patients with metastatic esophageal squamous cell carcinoma (ESCC)? Findings: At a willingness-to-pay threshold of $38,223.34/QALY, sintilimab was cost-effective in 84.4% of the simulations, the highest of the ICIs. Meaning: Sintilimab was the most cost-effective option compared to other ICIs as the second-line therapy for ESCC in China. [ABSTRACT FROM AUTHOR]

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of nonsmall-cell lung cancer (NSCLC), which is resistant to chemotherapy and radiotherapy with a poor prognosis. PSC is highly malignant and is prone to recurrence even after surgery. The programmed death-ligand 1 (PD-L1) tumor cell proportion score (TPS) 5%, TERT and TP53 gene mutations were detected in this patient accompanied by multiple metastatic sites. The anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI) that could be effective for advanced NSCLC and some sarcoma patients. Limited clinical trials and case reports have shown that PSC patients with gene mutations and PD-L1 expression have good responses tomultitarget antiangiogenic drug and immune checkpoint inhibitors (ICIs). In this article, we reported a casewith metastatic PSC diagnosed by Computed Tomography (CT)-guided needle biopsy treated with immunotherapy combined with antiangiogenic drugs as a neoadjuvant chemotherapy (NACT). PSC is controlled and the patient achieves successfully limb salvage treatment by surgical resection. Therefore, targeted therapy and immunotherapy can provide sufficient surgical opportunities for limb salvage in the treatment of metastatic PSC patients. Case summary: A 69-year-old male diagnosed with malignant bone tumor in the proximal femur was admitted to our hospital in June 2022 with recurrent fever as well as swelling and pain in the left thigh for twenty days. The initial computed tomography (CT) scan of the chest showed a pulmonary cavity (20 mm × 30 mm) and scattered lung masses. Subsequently, he underwent a CT-guided needle biopsy to distinguish the essence of osteolytic bone destruction and soft tissue mass in the left proximal femur which showed metastatic sarcomatoid carcinoma histology. Genetic testing revealed TERT c.-124C mutation (abundance 8.81%), TP53 p.R342 mutation (abundance 11.35%), tumor mutational burden (TMB) 7.09 muts/Mb, microsatellite stability (MSS), and PD-L1 (SP263) TPS 5% were also detected. The patient was tentatively treated with a combination of antiangiogenic drug and PD-1 inhibitor. After one course, the tumor volume significantly reduced in magnetic resonance imaging (MRI) and pathological fracture occurred in the femur after combined treatment. The patient received proximal femoral tumor resection and prosthesis replacement after defervescence. Sequentially sintilimab with anlotinib were administered for over 1 year. Finally, the local tumor was well controlled, and no obvious drug-related adverse reactions were observed. The lesions in the lung remained in partial response (PR) formore than 16months and complete response (CR) ofmetastatic tumor in the proximal femur was observed through imaging examinations. Conclusion: This is the first reported case of a metastatic PSC in femur showing a favorable response to the treatment consisting of anlotinib combined with sintilimab. This case suggests that antiangiogenic therapy combined with immunotherapy may benefit patients with metastatic PSC in the preoperative adjuvant therapy for limb salvage. [ABSTRACT FROM AUTHOR]

Sarcomatoid carcinoma (SC) is a rare, complex, aggressive tumor that spreads rapidly, is highly malignant, and has metastasized. Surgical resection is the primary treatment, and it usually occurs in the lungs and kidneys but rarely in the neck. Patients with advanced sarcomatoid carcinoma (SC) of the head and neck (HN) have a poor progonsis. In recent years, immune checkpoint inhibitors (ICIs) have been established as treatments for many solid tumors; however, the effectiveness of ICIs in treating SC of HN is still little recognized. We report a case study of a middle-aged woman with primary sarcomatoid carcinoma of the neck. She developed sarcomatoid carcinoma of the contralateral neck 7 months after the first surgical treatment. Subsequently, disease recurrence and metastasis occurred 8 months after the second surgery. The patient did not receive any treatment after both surgeries. The tumor showed high programmed death-ligand 1 (PD-L1) expression, with a combined positive score (CPS): 95. The patient's response to treatment was assessed as partial remission (PR) after 2 cycles of anlotinib combined with sintilimab. The patient has survived for over 2 years and remains in PR status, despite experiencing grade 2 hypothyroidism as an adverse event during treatment. The case highlights the efficacy and safety of anlotinib and sintilimab as a first-line treatment. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cholangiocarcinoma (CCA) is a highly heterogeneous tumor that occurs in the bile duct epithelium; adenosquamous carcinoma is a rare pathological subtype of CCA. The clinical treatment of patients with metastatic distal CCA poses significant challenges. We report a 53-year-old female diagnosed with a stage III adenosquamous carcinomas of distal CCA. Metastasis occurred 4 months postoperatively and she was diagnosed with stage IV disease. The patient was treated with Gemcitabine + Oxaliplatin (GEMOX) and Capecitabine + Oxaliplatin (CAPEOX), followed by sintilimab monotherapy. After two cycles of treatment, the patient achieved partial response (PR) and the lesion continued to shrink. After 37 months of follow-up, the patient's liver metastasis had almost completely disappeared, and complete response (CR) was achieved. Moreover, she had more than 46 months of disease progression-free survival (PFS). Immunohistochemical testing showed high expression of PD-L1, and next-generation sequencing revealed the presence of mutations in DNA damage repair (DDR) pathway genes. To the best of our knowledge, this is the first reported case of the successful treatment of metastatic distal adenosquamous CCA with sintilimab alone. Remarkably, patients of CCA with high PD-L1 expression and DDR pathway gene mutations may benefit from sintilimab treatment. [ABSTRACT FROM AUTHOR]

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials. [ABSTRACT FROM AUTHOR]

Background & Aims: Our retrospective study has suggested encouraging outcomes of lenvatinib combined with PD‐1 inhibitor and transarterial chemoembolization (TACE) on advanced hepatocellular carcinoma (HCC). This phase II trial was conducted to prospectively investigate the efficacy and safety of lenvatinib, sintilimab (a PD‐1 inhibitor) plus TACE (Len‐Sin‐TACE) in patients with advanced stage HCC. Methods: This was a single‐arm phase II trial. Patients with BCLC stage C HCC were recruited. They received lenvatinib (bodyweight ≥60 kg, 12 mg; bodyweight <60 kg, 8 mg) orally once daily, sintilimab (200 mg) intravenously once every 3 weeks, and on demand TACE. The primary endpoint was progression‐free survival (PFS) per mRECIST. Results: Thirty patients were enrolled. The primary endpoint was met with a median PFS of 8.0 (95% confidence interval [CI]: 6.1–9.8) months per mRECIST, which was the same as that per RECIST 1.1. The objective response rate was 60.0% per mRECIST and 30.0% per RECIST 1.1. The disease control rate was 86.7% per mRECIST/RECIST 1.1. The median duration of response was 7.4 (95% CI: 6.6–8.2) months per mRECIST (n = 18) and 4.3 (95% CI: 4.0–4.6) months per RECIST 1.1 (n = 9). The median overall survival was 18.4 (95% CI: 14.5–22.3) months. Treatment‐related adverse events (TRAEs) occurred in 28 patients (93.3%) and grade 3 TRAEs were observed in 12 patients (40.0%). There were no grade 4/5 TRAEs. Conclusions: Len‐Sin‐TACE showed promising antitumour activities with a manageable safety profile in patients with advanced stage HCC. The preliminary results need to be further evaluated with phase III randomized trials. [ABSTRACT FROM AUTHOR]

Background: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. Methods: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m² docetaxel, 80 mg/m2 oxaliplatin, 200 mg/m² calcium levofolinate, 2600 mg/m² 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. Results: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgerywith anR0 resection rateof93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9%(95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade =3 treatmentrelated adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population. [ABSTRACT FROM AUTHOR]

Introduction: The updated ORIENT-11 study demonstrated that sintilimab, when combined with chemotherapy, had promising survival advantage compared to standard chemotherapy alone in the first-line treatment for previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (nsNSCLC). This study aims to evaluate the cost-effectiveness of sintilimab plus chemotherapy for advanced nsNSCLC from a Chinese societal perspective. Methods: A partitioned survival model with a embedded decision tree was developed to assess the economic value of sintilimab plus chemotherapy over a lifetime horizon. Clinical data was captured from the updated ORIENT-11 study, while costs, health productivity losses, and utility values were collected from a nationwide cross-sectional survey in tertiary hospitals across multiple provinces in China. The primary outcomes were measured using the metrics of quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Costs and health outcomes were discounted at an annual rate of 5% per annum. Sensitivity analyses, including one-way and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses, were performed. Results: Compared to standard chemotherapy, treatment with sintilimab plus chemotherapy incurred a mean total cost of $23,979 and gained 0.98 QALYs over the lifetime horizon, resulting in an ICER of $24,568 per QALY gained. The use of sintilimab accumulated direct non-medical costs of $9262 and indirect costs of $6780 over 16 years. Probabilistic sensitivity analyses showed an 84.2% probability of sintilimab plus chemotherapy being cost-effective at a threshold of three times China's per capita gross domestic product in 2022 ($38,201). The model was most sensitive to the discount rate of QALYs and costs, as well as the costs of pemetrexed, sintilimab, and subsequent therapy in progressive disease state. Subgroup analyses indicated favorable incremental net monetary benefits in all subgroups. Conclusion: Sintilimab plus chemotherapy is a cost-effective first-line treatment therapy for advanced nsNSCLC in China when compared to standard chemotherapy. These findings, along with the improved progression-free survival and overall survival (OS) observed in ORIENT-11, support the use of this regimen in eligible candidates for advanced nsNSCLC. [ABSTRACT FROM AUTHOR]

Several immune related adverse events (irAEs) were reported with the wide application of immune checkpoint inhibitors (ICIs) in tumors. ICI-related skin reactions are the most common, which are manifested as maculopapules, rash, pruritus, vitiligo, psoriasis, and lichenoid rash.Among them, the incidence of pruritus is second only to maculopapule/rash, but both often co-exist. The severity of pruritus is mostly mild to moderate and can be relieved after symptomatic treatment with antihistamines. Symptoms are slightly relieved after conventional treatment in patients with severe pruritus, but it easily recurs and eventually develops into refractory pruritus.The patient's quality of life may be affected and may also be life-threatening.We report a case of a patient with postoperative recurrence of gallbladder neuroendocrine carcinoma,who developed refractory pruritus after sintilimab use, which was relieved after naloxone infusion after unsuccessful conventional drug therapy. By analyzing the treatment plan of this typical case of immune-related refractory pruritus after using sintilimab, this report discusses how clinical pharmacists can provide individualized treatment of patients by using their expertise and clinicians' cooperation and complementation in treating clinically difficult cases. This case report may be used as a reference in treating patients with refractory pruritus after the clinical use of sintilimab.

Abstract Background There are differences in the pharmacoeconomics of Immune checkpoint blocking (ICB) therapies for the treatment of lung squamous cell carcinoma (LSCC). However, no corresponding review studies have fully discussed the cost-effectiveness of ICBs in treating LSCC. The aim of this paper is to systematically review and evaluate all available pharmacoeconomic studies of ICBs for LSCC. Method The inclusion criteria were based on the population, intervention, comparator, outcomes, and study designs. An electronic search was conducted by June 2023, and the following databases were used: PubMed, EMBASE, Cochrane Library, and Web of Science. Search keywords included ‘Carcinoma’, Non-Small-Cell Lung’, ‘Immunotherapy’, and ‘Economics, Medical’. The primary outcome was the cost-effectiveness analysis of ICB therapy in LSCC patients. Drummond Checklist was used to assess quality problems and possible bias in the study design of included pharmacoeconomic studies. Results This review searched 15 articles on the economic evaluation of ICB treatment for LSCC. After a qualitative review of 15 studies, we concluded that nivolumab is more cost-effective as a monotherapy than chemotherapy alone. In the combination regimen, pembrolizumab combined with chemotherapy appears to be the most cost-effective option at present, but for Chinese payers with LSCC, locally developed treatments such as sintilimab or toripalimab in combination with chemotherapy are more cost-effective. Discussion The inclusion of economic evaluation has heterogeneity in research design and outcomes, which can only support qualitative synthesis. Therefore, The results of this paper need to be treated with caution. For the Chinese market, instead of imported drugs, the possible cost-effectiveness of locally developed ICB therapies should be the focus of future research.

Abstract Purpose There are limited and no standard therapies for recurrent glioblastoma. We herein report the antitumour activity and safety of sintilimab, bevacizumab and temozolomide (TMZ) in recurrent glioblastoma. Methods We retrospectively analysed eight patients with recurrent glioblastoma treated with sintilimab (200 mg) every three weeks + bevacizumab (10 mg/kg) every three weeks + TMZ (200 mg/m²orally) (5 days orally every 28 days for a total of four weeks). The primary objective was investigator-assessed median progression-free survival(mPFS). Secondary objectives were to assess the 6-month PFS, objective response rate (ORR) and duration of response (DOR) accroding to RANO criteria. Results The mPFS time for 8 patients was 3.340 months (95% CI: 2.217–4.463), The longest PFS was close to 9 months. Five patients were assessed to have achieved partial response (PR), with an overall remission rate of 62.5%, Four patients experienced a change in tumour volume at the best response time of greater than 60% shrinkage from baseline, and one patient remained progression free upon review, with a DOR of more than 6.57 months. The 6-month PFS was 25% (95% CI: 5.0–55.0%). Three patients had a treatment-related adverse events, though no grade 4 or 5 adverse events occurred. Conclusion In this small retrospective study, the combination regimen of sintilimab, bevacizumab and TMZ showed promising antitumour activity in treatment of recurrent glioblastoma, with a good objective remission rate.

Objective: To explore the safety and efficacy of metastatic osteosarcoma treatment with combined sintilimab injection and chemotherapy. Methods: We performed a retrospective analysis of 32 patients with metastatic osteosarcoma admitted to the Affiliated Hospital of Beihua University between January 2019 and June 2020. The sample was divided into an observation group, treated with sintilimab injection combined with chemotherapy (n= 16) and a control group, treated with chemotherapy (n = 16). Clinical efficacy and adverse reactions were compared between the two groups. Results: The overall response rates were 68.75% in the observation group and 31.25% in the control group (p < 0.05). The incidences of adverse reactions were 56.25% in the observation group and 81.25% in the control group. This was not a significant difference. In the observation group, the progression-free survival time was 8.13 ± 2.50 months, and the overall survival time was 22.75 ± 4.95 months. These were both significantly longer than the respective 6.44 ± 1.93 months and 19.69 ± 2.68 months in the control group (p < 0.05). Conclusion: The treatment of metastatic osteosarcoma with combined sintilimab injection and chemotherapy was found to prolong progression-free survival and overall survival time without increasing the incidence of adverse reactions. [ABSTRACT FROM AUTHOR]

[Display omitted] No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab. [ABSTRACT FROM AUTHOR]

Background: The synergistic effectiveness of combining immune checkpoint inhibitors with targeted therapies has shown promise in improving the conversion rate for unresectable hepatocellular carcinoma (HCC) patients to a potentially resectable status. However, the efficacy of this approach in the context of HCC with extrahepatic metastasis remains to be conclusively determined. Case presentation: We report a rare case of advanced HCC with extrahepatic metastasis who achieved long-term survival by a combination of systemic therapy (sintilimab and sorafenib) followed by laparoscopic hepatectomy. A 63-year-old man presented at our hospital with discomfort on the right side of his waist. An enlarged right hepatic lobe mass was subsequently revealed by CT scan. The patient's medical history, including a prior infection with hepatitis B virus, cirrhosis of the liver and an alpha-fetoprotein (AFP) level measuring 41.28 ng/ml substantiated the clinical diagnosis of HCC. On October 30th, 2019, the patient received 200 mg sintilimab intravenously (q3w) plus 200-400 mg BID sorafenib orally, along with antiviral therapy. After six cycles, his disease achieved partial response (PR). On April 26th, 2021, He underwent a laparoscopic hepatectomy. The patient achieved a sustained period of no evidence of disease for 2.5 years and with drug-free survival for 2 years after the resection. His current overall survival is estimated at approximately 4 years. Conclusions: This case highlights the potential of combining sintilimab and sorafenib in transforming HCC with extrahepatic metastasis into a condition amenable to surgical resection, suggesting that this treatment approach, followed by surgery, may lead to complete remission. [ABSTRACT FROM AUTHOR]

Chromophobe renal cell carcinoma (ChRCC) is a rare pathological type of renal cell carcinoma (RCC). Related systematic studies involving large numbers of patients are lacking, and more importantly, there is currently no international consensus on post-line treatment guidelines for ChRCC. The rapid development of systemic treatment with molecular targeted therapies and immune checkpoint inhibitors has brought effective approaches for patients with clear cell renal cell carcinoma (ccRCC), while progress in the treatment of ChRCC is still limited. In this case report, the patient was initially diagnosed at the early stage; 4 years post-surgery, she developed lung metastases and the disease progressed once again after being treated with sunitinib monotherapy for 3 years. However, after combining the immunotherapy sintilimab with the targeted therapy axitinib as second-line treatment, imageological examination showed lesions in the lungs that gradually decreased, and the bone metastases remained stable. To date, the patient has been continuously treated for over 2 years and is still undergoing regular treatment and follow-up. This case is the first to report the long-term survival of metastatic disease by using this treatment regimen and to propose a potential therapeutic option for patients with metastatic ChRCC. Since only one case was observed in this report, further study is needed. [ABSTRACT FROM AUTHOR]