1Department of Imaging Center, Shijiazhuang People's Hospital, Shijiazhuang 050011, China; 2Department of Radiotherapy, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
Abstract：Objective To investigate the efficacy of camrelizumab combined with second-line therapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the real-world settings. Methods Clinical data of 48 patients with esophageal cancer who met the inclusion criteria were retrospectively analyzed. The types of failure after first-line treatment, clinical efficacy, side effects and prognostic factors of second-line treatment were analyzed. SPSS 25.0 software was used for statistical analysis. Count data were expressed by composition ratio and analyzed by Chi-square test or Fisher's exact test. Survival analysis was conducted by Kaplan-Meier curve and log-rank test. Non-normally distributed data were recorded with the median, range and quartile. Results There were 26, 14, and 4 cases of combined chemoradiotherapy, chemotherapy and radiotherapy in the treatment of second-line camrelizumab, and 4 cases received immunotherapy alone. The median duration of immunotherapy was 6 cycles (range, 2-39 cycles). After second-line treatment, the short-term efficacy of 17, 27 and 4 cases was partial remission (PR), stable disease (SD) and progressive disease (PD), respectively. The overall response rate (ORR) was 35.4% and disease control rate (DCR) was 91.7%. The 1- and 2-year OS rates were 42.9% and 22.5%, and 1- and 2-year PFS rates were 29.0% and 5.8%. The median OS and PFS were 9.0 months (95%CI=6.4-11.7) and 8.5 months (95%CI=1.5-5.6), respectively. Multivariate analysis showed that combined immunotherapy mode, number of cycles of immunotherapy and short-term efficacy were the independent prognostic indicators affecting OS in this group of patients (HR=2.598, 0.222, 8.330, P=0.044, <0.001, <0.001). Lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), combined immunotherapy mode and short-term efficacy were the independent prognostic indicators affecting PFS in this group (HR=3.704, 3.598, 6.855, 2.159, 2.747, P=0.009, 0.008, <0.001, 0.049, 0.012). Conclusions Camrelizumab combined with second-line therapy can bring survival benefit to patients with recurrent or metastatic ESCC after first-line therapy, especially immunotherapy combined with chemoradiotherapy can significantly provide survival benefit. Peripheral blood inflammatory biomarkers are independent indicators affecting clinical prognosis of patients. Patients with better short-term efficacy also achieve better prognosis. The final conclusion remains to be validated by a large number of randomized controlled studies.
Gao Hongmei,Zhao Xiaohan,Wen Jingyuan et al. Preliminary analysis of immunotherapy combined with second-line treatment for esophageal squamous cell carcinoma patients[J]. Chinese Journal of Radiation Oncology, 2023, 32(7): 592-598.
[1] Sung H, Ferlay J, Siegel RL, et al.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021,71(3):209-249. DOI: 10.3322/caac.21660. [2] Jingu K, Umezawa R, Yamamoto T, et al.Patterns of failure after salvage chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer: 20-year experience in a single institution in Japan[J]. Esophagus, 2022,19(4):639-644. DOI: 10.1007/s10388-022-00922-9. [3] Obermannová R, Alsina M, Cervantes A, et al.Oesophageal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up[J]. Ann Oncol, 2022,33(10):992-1004. DOI: 10.1016/j.annonc.2022.07.003. [4] Bardol T, Ferre L, Aouinti S, et al. Survival after multimodal treatment including surgery for metastatic esophageal cancer: a systematic review[J]. Cancers (Basel), 2022,14(16)DOI: 10.3390/cancers14163956. [5] Ott PA, Elez E, Hiret S, et al.Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study[J]. J Clin Oncol, 2017,35(34):3823-3829. DOI: 10.1200/JCO.2017.72.5069. [6] Shah MA, Kojima T, Hochhauser D, et al.Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study[J]. JAMA Oncol, 2019,5(4):546-550. DOI: 10.1001/jamaoncol.2018.5441. [7] Sun JM, Shen L, Shah MA, et al.Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE- 590): a randomised, placebo-controlled, phase 3 study[J]. Lancet, 2021,398(10302):759-771. DOI: 10.1016/S0140-6736(21)01234-4. [8] Kato K, Cho BC, Takahashi M, et al.Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2019,20(11):1506-1517. DOI: 10.1016/S1470-2045(19)30626-6. [9] Huang J, Xu J, Chen Y, et al.Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study[J]. Lancet Oncol, 2020,21(6):832-842. DOI: 10.1016/S1470-2045(20)30110-8. [10] Shen L, Kato K, Kim SB, et al.Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): a randomized phase III study[J]. J Clin Oncol, 2022,40(26):3065-3076. DOI: 10.1200/JCO.21.01926. [11] Ni W, Yang J, Deng W, et al.Patterns of recurrence after surgery and efficacy of salvage therapy after recurrence in patients with thoracic esophageal squamous cell carcinoma[J]. BMC Cancer, 2020,20(1):144. DOI: 10.1186/s12885-020-6622-0. [12] Mummudi N, Jiwnani S, Niyogi D, et al. Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis[J]. Dis Esophagus, 2022,35(3):doab020. DOI: 10.1093/dote/doab020. [13] 王玉, 祝守慧, 刘宁, 等. 信迪利单抗治疗复发或转移晚期食管癌患者疗效初步观察[J].中华肿瘤防治杂志,2020,27(22):1838-1843. DOI: 10.16073/j.cnki.cjcpt.2020. 22.11. Wang Y, Zhu SH, Liu N, et al.Clinical study on the efficacy and safety of anti-PD-1 immunotherapy in the treatment of recurrent or metastatic advanced esophageal cancer[J].Chinese Journal of Cancer Prevention and Treatment,2020,27(22):1838-1843. DOI: 10.16073/j.cnki.cjcpt.2020.22.11. [14] Van Cutsem E, Kato K, Ajani J, et al.Tislelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (RATIONALE 302): impact on health-related quality of life[J]. ESMO Open, 2022,7(4):100517. DOI: 10.1016/j.esmoop.2022.100517. [15] Wei T, Ti W, Song Q, et al.Study of PD-1 inhibitors in combination with chemoradiotherapy/chemotherapy in patients with esophageal squamous carcinoma[J]. Curr Oncol, 2022,29(5):2920-2927. DOI: 10.3390/curroncol 29050238. [16] Gao LR, Wang X, Han W, et al.A multicenter prospective phase III clinical randomized study of simultaneous integrated boost intensity-modulated radiotherapy with or without concurrent chemotherapy in patients with esophageal cancer: 3JECROG P-02 study protocol[J]. BMC Cancer, 2020,20(1):901. DOI: 10.1186/s12885-020- 07387-y. [17] Ito R, Nakamura Y, Sunakawa H, et al.Tumor response and survival outcomes of salvage concurrent chemoradiotherapy with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy for postoperative locoregional recurrence of esophageal squamous cell carcinoma[J]. Esophagus, 2022,19(4):645-652. DOI: 10.1007/s10388-022- 00936-3. [18] Yang G, Sun H, Zhou C, et al.PD-1 inhibitor monotherapy versus combination therapy: a real-world study of patients with recurrent or metastatic advanced esophageal squamous cell carcinoma after first-line chemotherapy[J]. J Cancer Res Ther, 2022,18(2):545-552. DOI: 10.4103/jcrt.jcrt_125_22. [19] Wang C, Jin L, Cheng X, et al.Real-world efficacy and safety of sintilimab-based regimens against advanced esophageal cancer: a single-center retrospective observational study[J]. Biomed Res Int, 2022,2022:7331687. DOI: 10.1155/2022/7331687. [20] Spigel DR, Faivre-Finn C, Gray JE, et al.Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer[J]. J Clin Oncol, 2022,40(12):1301-1311. DOI: 10.1200/JCO.21.01308. [21] Waterhouse DM, Garon EB, Chandler J, et al.Continuous versus 1-year fixed-duration nivolumab in previously treated advanced non-small-cell lung cancer: CheckMate 153[J]. J Clin Oncol, 2020,38(33):3863-3873. DOI: 10.1200/JCO.20.00131. [22] Zhao Q, Bi Y, Xue J, et al.Prognostic value of absolute lymphocyte count in patients with advanced esophageal cancer treated with immunotherapy: a retrospective analysis[J]. Ann Transl Med, 2022,10(13):744. DOI: 10.21037/atm-22-2669. [23] Shrihari TG.Dual role of inflammatory mediators in cancer[J]. Ecancermedicalscience, 2017,11:721. DOI: 10.3332/ecancer.2017.721. [24] Suzuki T, Ishibashi Y, Tsujimoto H, et al.A novel systemic inflammatory score combined with immunoinflammatory markers accurately reflects prognosis in patients with esophageal cancer[J]. In Vivo, 2020,34(6):3705-3711. DOI: 10.21873/invivo.12218. [25] Li B, Xiong F, Yi S, et al.Prognostic and clinicopathologic significance of neutrophil-to-lymphocyte ratio in esophageal cancer: an update meta-analysis[J]. Technol Cancer Res Treat, 2022,21:15330338211070140. DOI: 10.1177/15330338211070140. [26] Ji WH, Jiang YH, Ji YL, et al.Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy[J]. Dis Esophagus, 2016,29(5):403-411. DOI: 10.1111/dote.12322. [27] Zhang Y, Han N, Zeng X, et al.Impact of platelets to lymphocytes ratio and lymphocytes during radical concurrent radiotherapy and chemotherapy on patients with nonmetastatic esophageal squamous cell carcinoma[J]. J Oncol, 2022,2022:3412349. DOI: 10.1155/2022/3412349.
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