Search for prognostic factors when prescribing immunotherapy in the second line of treatment for metastatic gastric cancer

Abstract

Introduction. It has been previously reported that the effectiveness of therapy with immune checkpoint inhibitors (ICI) in the second line of metastatic gastric cancer was not higher than with cytostatic therapy, and did not depend on the level of PD-L1 CPS and the presence of MSI. At the same time, 28 % of patients lived more than 2 years after starting therapy. Aim . To identify the criteria for predicting overall survival (OS) in patients receiving second-line ICI therapy. Materials and methods . We assessed 91 patients with morphologically confirmed metastatic gastric or cardioesophageal junction cancer who progressed during the 1st line of treatment and received ICI therapy in the 2nd line. The median follow-up time was 54.2 months (28–90 months). Patient characteristics : 53.8 % of patients were males; average age — 65.7 years (34.1–85.7); ECOG 2 performance status in 9.9 %; synchronous metastases — 56 %; liver / peritoneum metastases — 69.3 %; metastases in 3 or more organs — 17.6 %; CPS > 10–41.8 %; MSI — 43.5 %. Results. A univariate analysis which included 22 indicators showed a negative effect on OS after 1st line therapy with PFS < 8 months, LDH level > 248 U / L, neutrophil / lymphocyte ratio (NLR) < 2.35, platelet / neutrophil ratio (PNR) > 168.7. In multifactorial analysis, significance was stated for the 1st line with PFS > 8 months (HR 3.541; 95 % CI 1.186–10.576, p = 0.024) and LDH level < 248 U / l (HR 4.606; 95 % CI 1.847–11.484, p = 0.001). When assessing long-term outcomes in patients with or without risk factors, we found that in the absence of negative prognostic factors the mPFS was 19.7 months, while in the presence it was only 3.4 months (HR 3.47; 95 % CI 1.2–10.03, p = 0.022). The OS was 33.4 months and 5.4 months. (HR 4.028; 95 % CI 1.376–11.793, p = 0.011), respectively. When comparing these groups by their main characteristics, we noticed that there were no differences in ECOG status, the number of organs with metastases, the frequency of CPS ≥ 10 and MSI. Conclusions. The results obtained leave a reasonable assumption that a group of patients on the 1st line had PFS > 8 months and a normal baseline LDH level. And they had real benefits from ICI therapy with the 2nd line therapy for metastatic gastric cancer. However, a more accurate validation requires a prospective study.