Camrelizumab plus apatinib as second-line treatment for advanced oesophageal squamous cell carcinoma (CAP 02): a single-arm, open-label, phase 2 trial

Meng, Xiangrui; Wu, Tao; Hong, Yonggui; Fan, Qingxia; Ren, Zhonghai; Guo, Yanzhen; Yang, Xiuli; Shi, Peng; Yang, Jiamei; Yin, Xianzhe; Luo, Zhiquan; Xia, Jin; Zhou, Yue; Xu, Mengli; Liu, Enjie; Jiang, Guozhong; Li, Shenglei; Zhao, Feng; Ma, Chi; Hou, Zhiguo; Li, Jing; Wang, Junsheng; Wang, Feng

doi:10.1016/s2468-1253(21)00378-2

Cited by 44 publications

(38 citation statements)

References 29 publications

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“…The median PFS was 6.8 months (95% CI, 3.8 to 10.4 months) and the median OS was 15.8 months (95% CI, 8.4 to 16.2 months). 23 (44%) of 52 patients had treatment-related grade 3-4 adverse events including increased gamma-glutamyltransferase (19%), increased aspartate aminotransferase (19%), and increased alanine aminotransferase (10%) ( 74 ). As a potential second-line treatment provided an option for patients with advanced esophageal squamous cell carcinoma and the safety was controllable.…”

Section: Clinical Efficacy In Esophageal Squamous Cell Carcinomamentioning

confidence: 99%

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Huang

Zhang

et al. 2022

Front. Immunol.

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Digestive system malignancies are one of the primary causes of cancer-related death. Meanwhile, angiogenesis has been proved to play an important role in the process of cancer neovascularization. Apatinib, a novel targeted antiangiogenic molecule, could generate highly selective competition in the vascular endothelial growth factor receptor-2, involved in tumor progression and metastasis. It has been implied as a promising cancer treatment agent that can prevent tumor cell proliferation meanwhile inhibit tumor angiogenesis. Furthermore, completed clinical trials demonstrated that apatinib could prolong the progression-free survival and overall survival in advanced gastric cancer and primary liver cancer. Recent studies revealed that apatinib had a synergistic effect with immunotherapy as a second-line and third-line treatment regimen for some other cancers. In this review, we summarize the pharmacological properties of apatinib and the latest clinical application in chemotherapy-refractory patients with advanced digestive system cancer. Based on the comparable survival results, the molecular mechanisms of apatinib are prospective to include the antiangiogenic, apoptosis-inducing, and autophagy-inducing properties in the corresponding signaling pathway. Treatment of apatinib monotherapy or combination immunotherapy remains the optimal option for patients with digestive system malignancies in the future.

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Section: Clinical Efficacy In Esophageal Squamous Cell Carcinomamentioning

confidence: 99%

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Huang

Zhang

et al. 2022

Front. Immunol.

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“…The therapeutic efficacy of the combination of PD-1 inhibitors plus apatinib in patients with advanced cancer, including esophageal squamous cell carcinoma, gestational trophoblastic neoplasia, biliary tract cancer, and hepatocellular carcinoma, among other cancers, has been reported by previous studies ( 19 – 22 ). These studies have suggested that PD-1 inhibitors plus apatinib may be a promising strategy for advanced cancers.…”

Section: Introductionmentioning

confidence: 63%

“…The safety of PD-1 inhibitors plus apatinib in advanced CRC has not been reported. In contrast, in other cancers, it has been reported that the most common grade 3 or worse adverse events of PD-1 inhibitors plus apatinib include increased aspartate aminotransferase and increased gamma-glutamyl transferase in patients with advanced esophageal squamous cell carcinoma ( 19 ). Hypertension, rash, and neutropenia are the primary grade 3 treatment-related adverse events in patients with chemorefractory or relapsed gestational trophoblastic neoplasia treated with a PD-1 inhibitor plus apatinib ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Treatment Response, Survival Benefit and Safety Profile of PD-1 Inhibitor Plus Apatinib Versus Apatinib Monotherapy in Advanced Colorectal Cancer Patients

Pan

Liang

et al. 2022

Front. Oncol.

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PurposeProgrammed cell death protein 1 (PD-1) inhibitor plus apatinib is reported to be a promising strategy for advanced cancers. Moreover, a PD-1 inhibitor or apatinib exerts a certain efficacy in advanced colorectal cancer (CRC), whereas their synergistic effect is unclear. This study aimed to evaluate the treatment efficacy and safety of a PD-1 inhibitor plus apatinib in advanced CRC patients.MethodsIn total, 45 advanced CRC patients who received a PD-1 inhibitor plus apatinib (PD-1 inhibitor plus apatinib group, N=20) or apatinib monotherapy (apatinib group, N=25) as third-line therapies were enrolled in the current study.ResultsThe objective response rate (20.0% vs. 8.0%) (P=0.383) and disease control rate (70.0% vs. 52.0%) (P=0.221) were numerically increased in the PD-1 inhibitor plus apatinib group, respectively, compared with the apatinib group, but no statistical significance was observed. The median progression-free survival (PFS) was 7.5 versus 4.8 months; the 1-year PFS rate was 32.5% versus 9.9%; the median overall survival (OS) was 12.3 versus 8.7 months; and the 1-year OS rate was 50.7% versus 27.0% in the PD-1 inhibitor plus apatinib group versus the apatinib group, respectively. PFS (P=0.038) and OS (P=0.048) were prolonged in the PD-1 inhibitor plus apatinib group compared with the apatinib group. PD-1 inhibitor plus apatinib (versus apatinib) was independently associated with longer PFS (P=0.012) and OS (P=0.009). The majority of the adverse events were of grade 1-2, wherein the incidence was similar between groups, except for the fact that the incidence of capillary proliferation was elevated in the PD-1 inhibitor plus apatinib group compared with the apatinib group (25.5% versus 0.0%) (P=0.013).ConclusionPD-1 inhibitor plus apatinib presents a potential improvement in efficacy and survival benefit compared with apatinib monotherapy, with tolerable safety in advanced CRC patients.

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“…Clinical trials have been launched to evaluate the integration of ICIs and targeted therapy. In patients with advanced ESCC, a single-arm, phase II study analyzing the safety and the efficacy of camrelizumab plus apatinib as second-line treatment showed 34.6% of patients had an objective response, and 44% of patients had grade 3 or worse adverse events ( 51 ). The promising activity and manageable toxicity of the combination treatment indicated it might be an option for patients with advanced ESCC.…”

Section: Strategies To Overcome Drug Resistance and Future Directionsmentioning

confidence: 99%

Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer

et al. 2022

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As the predominant treatment option of the immunotherapy for advanced esophageal cancer (EC), the application of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors brings new hope to clinical practice. However, a considerable portion of patients do not response to this therapy, meanwhile most patients sensitive to PD-1 or PD-L1 antibody initially will develop resistance to the treatment eventually. To break through the limits of clinical effect, it is of critical importance to make a profound understanding of the mechanisms of so called primary resistance and acquired resistance. Subsequently, exploring potent predictors to identify suitable patients for anti-PD-1/PD-L1 treatment and investigating efficient strategies to overcome drug resistance will be helpful to expend the benefit of immunotherapy. In the present view, we summarized the potential predictive factors for anti-PD-1/PD-L1 immunotherapy in EC, and demonstrated the plausible mechanisms of resistance to PD-1/PD-L1 blockade as well as its feasible solutions.

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Camrelizumab plus apatinib as second-line treatment for advanced oesophageal squamous cell carcinoma (CAP 02): a single-arm, open-label, phase 2 trial

Cited by 44 publications

References 29 publications

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Treatment Response, Survival Benefit and Safety Profile of PD-1 Inhibitor Plus Apatinib Versus Apatinib Monotherapy in Advanced Colorectal Cancer Patients

Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer

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