Abstract:

Objective To investigate the efficacy of the combination of sintilimab and docetaxel in the treatment of cervical cancer and its impact on laboratory indicators. Methods A total of 86 patients with advanced cervical cancer treated at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2019 to June 2022 were selected as the study subjects. The patients were divided into a study group （n=43） and a control group （n=43） according to the treatment method. The study group was treated with a combination of sintilimab and docetaxel， while the control group was treated with docetaxel. After 6 cycles of treatment， the clinical efficacy， vascular endothelial growth factor receptor （VEGFR） levels， tumor marker levels， immune function indicators， programmed death-1 （PD-1）， programmed death-ligand 1 （PD-L1） levels， and adverse reactions during treatment between the two groups were compared. 1-year progression-free survival （PFS） rate and overall survival （OS） rate between the two groups of patients were compared. Results After 6 cycles of treatment， the objective response rates （ORR） of the study group and the control group were 48.84% （21/43） and 30.23% （13/43）， respectively， with no statistically significant difference （χ²=3.11， P=0.078）； the disease control rates （DCR） of the two groups were 86.05% （37/43） and 62.79% （27/43）， respectively， with a statistically significant difference （χ²=6.11， P=0.013）. Before treatment， the levels of VEGFR2 and VEGFR3 in the study group were （223.42±57.89）， （3.25±1.22） ng/L， respectively， while those in the control group were （220.56±58.45）， （3.31±1.17） ng/L， respectively， with no statistically significant differences （t=0.23， P=0.820； t=0.23， P=0.817）. After treatment， the VEGFR2 and VEGFR3 levels in the study group were （123.21±36.97）， （0.81±0.21） ng/L， respectively， while those in the control group were （151.22±37.34）， （1.33±0.37） ng/L， respectively， with statistically significant differences （t=3.50， P=0.001； t=8.02， P<0.001）. However， the levels of VEGFR2 and VEGFR3 in both groups of patients decreased after treatment compared to before treatment （all P<0.05）. Before treatment， the levels of carcinoembryonic antigen （CEA）， carbohydrate antigen 125 （CA125）， and squamous cell carcinoma antigen （SCC-Ag） in the study group were （8.73±1.02） ng/ml， （29.73±5.88） U/ml， and （7.23±1.34） ng/ml， respectively， while those in the control group were （8.41±1.23） ng/ml， （30.12±5.93） U/ml， and （7.37±1.43） ng/ml， respectively， with no statistically significant differences （t=1.31， P=0.193； t=0.31， P=0.760； t=0.47， P=0.641）. After treatment， the CEA， CA125， and SCC-Ag levels in the study group were （3.52±0.78） ng/ml， （13.28±1.82） U/ml， and （2.33±0.49） ng/ml， respectively， while those in the control group were （3.87±0.62） ng/ml， （14.12±1.72） U/ml， and （2.65±0.54） ng/ml， respectively， with statistically significant differences （t=2.30， P=0.024； t=2.20， P=0.031； t=2.88， P=0.005）. However， the levels of CEA， CA125， and SCC-Ag in both groups of patients decreased after treatment compared to before treatment （all P<0.05）. Before treatment， the T cell subsets CD4⁺， CD8⁺， and CD4⁺/CD8⁺ in the study group were （27.53±2.23） %， （29.34±3.78） %， and 0.93±0.33， respectively， while those in the control group were （28.32±2.31） %， （30.03±3.27） %， and 0.94±0.42， respectively， with no statistically significant differences （t=1.61， P=0.110； t=0.91， P=0.368； t=0.12， P=0.903）. After treatment， the T cell subsets CD4⁺， CD8⁺， and CD4⁺/CD8⁺ in the study group were （35.33±3.36） %， （44.32±4.33） %， and 0.80±0.22， respectively， while those in the control group were （30.31±3.23） %， （42.21±4.31） %， and 0.71±0.19， respectively， with statistically significant differences （t=7.06， P<0.001； t=2.27， P=0.026； t=2.03， P=0.046）. After treatment， the CD4⁺ and CD8⁺ T cell subsets in both groups were higher than before treatment， while the CD4⁺/CD8⁺ was lower than before treatment （all P<0.05）. Before treatment， the levels of PD-1 and PD-L1 mRNA in peripheral blood mononuclear lymphocytes of the study group were 1.21±0.21 and 0.73±0.15， respectively， while those in the control group were 1.23±0.25 and 0.79±0.14， respectively， with no statistically significant differences （t=0.40， P=0.689； t=1.92， P=0.059）. After treatment， the levels of PD-1 and PD-L1 mRNA in peripheral blood mononuclear lymphocytes of the study group were 0.77±0.13 and 0.52±0.13， respectively， while those in the control group were 0.93±0.19 and 0.66±0.17， respectively， with statistically significant differences （t=4.56， P<0.001； t=4.29， P<0.001）. However， the levels of PD-1 and PD-L1 mRNA in both groups of patients decreased after treatment compared to before treatment （all P<0.05）. The 1-year PFS rate and OS rate of the study group patients were 60.47% and 72.09%， respectively； while those in the control groups were 51.16% and 65.12%， respectively， with no statistically significant differences （χ²=1.31， P=0.253； χ²=0.82， P=0.365）. The incidences of digestive system response， abnormal liver and kidney function， hematuria， bone marrow suppression， and rash in the study group were 39.53% （17/43）， 13.95% （6/43）， 13.95% （6/43）， 23.26% （10/43）， and 37.21% （16/43）， respectively， while those in the control group were 32.56% （14/43）， 9.30% （4/43）， 11.63% （5/43）， 18.60% （8/43）， and 30.23% （13/43）， respectively， with no statistically significant differences （χ²=0.45， P=0.500； χ²=0.45， P=0.501； χ²=0.10， P=0.747； χ²=0.28， P=0.596； χ²=0.47， P=0.494）. Conclusions Compared with monotherapy with docetaxel， the combination of sintilimab and docetaxel has a higher DCR in the treatment of advanced cervical cancer. To a certain extent， it effectively reduces the expression levels of VEGFR， serum tumor markers， and PD-1， PD-L1 in peripheral blood mononuclear lymphocytes， improves the immune function of patients， and has comparable drug safety. However， the two treatment options have comparable 1-year survival rates.

Key words: Uterine cervical neoplasms, Immune checkpoint inhibitors, Docetaxel, Treatment outcome, Sintilimab