Safety and Feasibility of Radiotherapy Plus Camrelizumab for Locally Advanced Esophageal Squamous Cell Carcinoma

Abstract

Lessons Learned Radiotherapy plus anti–PD‐1 antibody as first‐line therapy is safe and feasible in locally advanced esophageal squamous cell carcinoma (ESCC). Tumor‐infiltrating and peripheral lymphocytes were associated with patient survival. Further studies combining chemoradiotherapy with immunotherapy in locally advanced ESCC and exploration of predictive biomarkers are warranted. Background We conducted a phase Ib study of radiotherapy plus programmed cell death protein 1 (PD‐1) monoclonal antibody camrelizumab as first‐line treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Methods We planned to enroll 20 patients with newly diagnosed locally advanced ESCC. Patients received 60 Gy radiation (2.0 Gy/fraction, 5 fractions/week), with camrelizumab (200 mg every 2 weeks) starting with radiotherapy and continuing for 32 weeks (i.e., for 16 cycles). The primary endpoints were safety and feasibility. Secondary endpoints were rates of radiologic and pathologic response, overall survival (OS), and progression‐free survival (PFS). Study data were collected by the week during radiotherapy (RT), every month during the maintenance camrelizumab treatment, and every 3 months after treatment. Tumor microenvironment and peripheral blood were monitored at baseline and after 40 Gy radiation for association with efficacy. Results Twenty patients were enrolled and received treatment. One patient (patient 10) was excluded upon discovery of a second tumor in the bladder during treatment, leaving 19 patients for analysis. Toxicity was deemed tolerable. Fourteen (74%) patients had assessed objective response. At a median follow‐up time of 31.0 months (95% confidence interval [CI], 27.0–35.1), median OS and PFS times were 16.7 months (95% CI, 5.9–27.9) and 11.7 months (95% CI, 0–30.3), respectively. OS and PFS rates at 24 months were 31.6% and 35.5%, respectively. Kaplan‐Meier analysis revealed associations between the following factors and OS/PFS: tumor programmed cell death ligand 1 (PD‐L1) expression, PD‐1+CD8+, PD‐1+CD4+ T cells, and PD‐L1+CD4+ T cells; peripheral blood CD4+, CD8+, CD4+ regulatory T cells, and their subsets. Conclusion Radiotherapy plus camrelizumab had manageable toxicity and antitumor efficacy for locally advanced ESCC. Several biomarkers were associated with clinical benefit and deserve further study.

Neoadjuvant camrelizumab plus chemotherapy in treating locally advanced esophageal squamous cell carcinoma patients: a pilot study

“…Subsequently, the current study turn attention to camrelizumab, a PD-1 immune checkpoint inhibitor, which blocks the binding site of PD-1 expressed on activated T lymphocytes, B cells, and natural killer cells to PD-L1 overexpressed on certain cancer cells. So far, several studies report that camrelizumab combined with chemotherapy has been used in adjuvant and second-line therapy of locally advanced ESCC and exhibits a promising antitumor efficacy [ 17 , 18 ]. However, the clinical value of neoadjuvant camrelizumab combined with chemotherapy in locally advanced ESCC is still unclear.…”

“…Camrelizumab, a domestic product developed in China, is a novel IgG4-kappa anti-PD-1 inhibitor that has been used for treatment of a variety of malignancies, such as refractory classical Hodgkin’s lymphoma and gastric or gastroesophageal junction adenocarcinoma [ 15 , 16 ]. Moreover, camrelizumab has been previously witnessed for adjuvant or second-line therapy of locally advanced ESCC [ 17 , 18 ]. However, the clinical value of neoadjuvant camrelizumab plus chemotherapy in the treatment for locally advanced ESCC has not been reported before.…”

Efficacy and safety of radiotherapy plus anti-PD1 versus transcatheter arterial chemoembolization plus sorafenib for advanced hepatocellular carcinoma: a real-world study

“…RT can undergo a so-called immunogenic death inducing in situ vaccination and render the tumor microenvironment conducive to effector T-cell 4 recruitment and function to produce a synergistic anti-tumor immunity with anti-PD1 for durable disease control [ 15 ]. Early clinical trials combining RT with anti-PD1 showed clinical activity in several cancers including non-small cell lung cancer [ 16 ], malignant pigmented tumor [ 17 ], and esophageal squamous cell carcinoma [ 18 ]. A case report including 5 cases showed the impressive tumor control in patients with advanced HCC treated by the combination of RT and anti-PD1 [ 19 ].…”

Spatial Distribution and Predictive Significance of Dendritic Cells and Macrophages in Esophageal Cancer Treated With Combined Chemoradiotherapy and PD-1 Blockade

“…Although radiotherapy evoked antitumor immune response, the proliferated T, B, and NK cells activated during radiotherapy were sensitive to radiation-induced cytotoxicity. Additionally, the on-treatment tumor biopsies were always collected during radiotherapy ( 5 , 26 ). As a result, poor relationship between the on-treatment tumor-infiltrating T cells and patient survival was observed in our present and previous study ( 4 ) ( 26 ).…”

“…Additionally, the on-treatment tumor biopsies were always collected during radiotherapy ( 5 , 26 ). As a result, poor relationship between the on-treatment tumor-infiltrating T cells and patient survival was observed in our present and previous study ( 4 ) ( 26 ). Identifying the functional status might provide clues of the antitumor immune characteristics of these radiosensitive immune cells in further studies.…”