Response Rate and Prognostic Impact of Salvage Chemotherapy after Nivolumab in Patients with Advanced Gastric Cancer

Abstract

Objective: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. Methods: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. Results: Twenty-two and nine patients received nivolumab as third-line and fourth-to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. Conclusion: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.

Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

“…For patients with progressive disease status after ICI treatment, another therapy sometimes could be administered to extend their life. Several studies have reported that salvage chemotherapy (SCT) administered after immunotherapy would be effective for patients with metastatic non-small-cell lung cancer (NSCLC), metastatic melanoma, B cell lymphoma, advanced gastric cancer, and metastatic urothelial carcinoma [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Furthermore, SCT has been reported to be an effective treatment for HNSCC in R/M as well as other carcinomas and is attracting attention as a sequential treatment [ 10 , 11 ].…”

Differential Dermatologic Adverse Events Associated With Checkpoint Inhibitor Monotherapy and Combination Therapy: A Meta-Analysis of Randomized Control Trials

“…In contrast, most PD-L1 antibodies prevent the interaction between PD-L1 and CD80 and between PD-L1 and PD-1, but not the interaction between PD-1 and PD-L2. Therefore, it is possible that depending on which interaction predominates in a particular cancer, PD-1 and PD-L1 antibodies may not have redundant activity (Arigami et al, 2020). Results from subgroup analysis showed that any grade pruritus and rash developed from PD-1 inhibitor were decreased FIGURE 6 | Forest plots of the relative risks and 95% CIs for pruritus and rash in comparison of combined immunotherapy and either monotherapy: (A) any grade pruritus for PD-1/-L1 plus CTLA-4 inhibitor compared to PD-1/-L1 inhibitor; (B) high grade pruritus for PD-1/-L1 plus CTLA-4 inhibitor compared to PD-1/-L1 inhibitor; (C) any grade rash for PD-1/-L1 plus CTLA-4 inhibitor compared to PD-1/-L1 inhibitor; (D) high grade rash for PD-1/-L1 plus CTLA-4 inhibitor compared to PD-1/-L1 inhibitor; (E) any grade pruritus for PD-1/-L1 plus CTLA-4 inhibitor compared to CTLA-4 inhibitor; (F) any grade rash for PD-1/-L1 plus CTLA-4 inhibitor compared to CTLA-4 inhibitor.…”

“…The major physiological role of CTLA-4 seems to be through distinct effects on the two main subsets of cluster of differentiation four positive (CD4 + ) T cells: down modulation of helper T cell activity and enhancement of regulatory T (Treg) cell immunosuppressive activity ( Bylicki et al, 2020 ; Cancela et al, 2020 ; Peggs et al, 2009 ). Blockade of the PD-1 pathway may enhance antitumor immune responses by diminishing the number and/or suppressive activity of intratumoral Treg cells ( Arigami et al, 2020 ). It is thought that PD-1 predominantly regulates effector T cell activity within tissue and tumors, whereas CTLA-4 predominantly regulates T cell activation ( Arigami et al, 2020 ).…”

“…Blockade of the PD-1 pathway may enhance antitumor immune responses by diminishing the number and/or suppressive activity of intratumoral Treg cells ( Arigami et al, 2020 ). It is thought that PD-1 predominantly regulates effector T cell activity within tissue and tumors, whereas CTLA-4 predominantly regulates T cell activation ( Arigami et al, 2020 ). Although dermatologic adverse events observed with ICIs used in combination are more frequent, more severe, and longer lasting ( Sibaud et al, 2016 ), combination immunotherapy has more extensive clinical applications due to improved efficacy.…”

“…In contrast, most PD-L1 antibodies prevent the interaction between PD-L1 and CD80 and between PD-L1 and PD-1, but not the interaction between PD-1 and PD-L2. Therefore, it is possible that depending on which interaction predominates in a particular cancer, PD-1 and PD-L1 antibodies may not have redundant activity ( Arigami et al, 2020 ). Results from subgroup analysis showed that any grade pruritus and rash developed from PD-1 inhibitor were decreased compared to PD-L1 inhibitor, while the comparison in high grade (3–5) rash did not reach a statistically significant level.…”