The application of immunotherapy combined with taxanes in second‑line treatment of advanced HER2 negative gastric cancer

Chen,Tianran; Xu,Meng; Xu,Jiajun; Zhan,Xianbao; Zhang,Yingyi; Ying,Mingzhen; Wu,Meihong

doi:10.3892/mco.2024.2806

The application of immunotherapy combined with taxanes in second‑line treatment of advanced HER2 negative gastric cancer

Authors:
- Tianran Chen
- Meng Xu
- Jiajun Xu
- Xianbao Zhan
- Yingyi Zhang
- Mingzhen Ying
- Meihong Wu
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Affiliations: Department of Oncology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, P.R. China
Published online on: November 21, 2024 https://doi.org/10.3892/mco.2024.2806
Article Number: 11
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human epidermal growth factor receptor‑2 (HER2) negative advanced gastric cancer (GC) has a high global incidence and mortality rate with limited options for second‑line treatment. Monotherapy is not effective and the combination of chemotherapy and immunotherapy has not yet been included in the guidelines. The present study aimed to explore a new treatment approach by conducting a single‑center, retrospective, observational real‑world study. A total of 21 patients with advanced HER2‑negative GC, who had progressed after receiving standard first‑line regimens [tegafur, gimeracil and oteracil potassium capsules (S‑1) or capecitabine plus oxaliplatin], were selected. The application of programmed cell death‑1 (PD‑1) inhibitor combined with taxanes was selected as the second‑line treatment. The primary outcomes measured were progression‑free survival (PFS), pathological complete response, objective response rate (ORR), disease control rate (DCR) and adverse reactions in the present patient cohort. The median (m)PFS in the overall population was 7.1 months, with a 95% confidence interval (CI) of 6.0‑8.2 months and the median overall survival (mOS) was 11.3 months, with a 95% CI of 4.5‑18.2 months. The ORR was 9.5% and the DCR was 90.5%. Univariate and multivariate analyses indicated that Ki67 <70% and tumor marker‑positive status [one or two increases among carcinoembryogenic antigen (CEA), cancer antigen (CA) 199 and CA125] were independent prognostic factors for PFS and overall survival (OS) in second‑line treatment. Significant statistical differences were noted in PFS (mPFS=5.3 months, 95% CI: 3.1‑7.5 months vs. mPFS=9.1 months, 95% CI: 6.2‑12.0 months; P=0.002) and OS (mOS=8.8 months, 95% CI: 7.0‑10.7 months vs. mOS=17.2 months, 95% CI: 16.0‑18.5 months; P=0.013) between the Ki67‑high group (Ki67 ≥70%) and the Ki67‑low group (Ki67 <70%). Significant statistical differences were noted in OS between tumor marker‑negative status (CEA, CA199 and CA125 within normal range) and tumor marker‑positive status (one or two increases among CEA, CA199 and CA125; mOS=17.2 months, 95% CI: 16.0‑18.4 months vs. mOS=8.8 months, 95% CI: 5.3‑12.4 months; P=0.018); however, no significant differences were noted in PFS between these two groups. The present study retrospectively analyzed the new second‑line approach of PD‑1 inhibitor combined with taxanes for HER2 negative GC which effectively improved patient PFS and OS compared with single‑agent chemotherapy. The expression levels of Ki67 and the tumor marker‑negative status possess potential clinical value in monitoring prognosis and guiding future individualized use of chemotherapy combined with immunotherapy.

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