Effects of proton pump inhibitors on outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors

doi:10.3760/cma.j.cn371439-20210315-00003

Abstract

Abstract:

Objective To evaluate the effects of proton pump inhibitors (PPIs) on the clinical outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors (ICIs). Methods A total of 204 patients with advanced solid tumors who received ICIs in the Affiliated Hospital of Yangzhou University from November 2016 to December 2020 were retrospectively analyzed. The patients were divided into PPIs group (n=73) and Non-PPIs group (n=131) according to whether they received PPIs within 1 month before or after the initiation of ICIs treatment. The correlations between the uses of PPIs and the clinical characteristics of patients were explored, and the clinical efficacy of the two groups was evaluated. Kaplan-Meier survival curve was applied to analyze the effects of PPIs uses on overall survival (OS) and progression-free survival (PFS) of patients. The Cox proportional hazards model was used to clarify whether PPIs was an independent indicator of patients' prognosis. Results During ICIs treatment of advanced solid tumors, the use of PPIs was not correlated with the patients' gender, age, tumor type, the score of the United States Eastern Collaborative Group, types of immunotherapy drugs and treatment strategy (all P>0.05). The objective response rate of the Non-PPIs group was better than that of the PPIs group (45.0% vs. 24.7%, χ²=8.286, P=0.004). The disease control rate of the Non-PPIs group was better than that of the PPIs group (75.6% vs. 52.0%, χ ²=11.755, P=0.001). In patients with advanced solid tumors, the median OS (3.4 months vs. 6.1 months) and median PFS (2.8 months vs. 4.0 months) in the PPIs group were shorter than those in the Non-PPIs group (χ ²=9.563, P=0.002; χ ²=5.761, P=0.016). Univariate analysis showed that among patients with advanced solid tumors treated with ICIs, PPIs uses was significantly correlated with OS (HR=1.85, 95%CI: 1.24-2.76, P=0.003); PPIs uses(HR=1.65, 95%CI: 1.09-2.51, P=0.019) and age (HR=1.56, 95%CI: 1.05-2.32, P=0.029) were significantly correlated with PFS. Multivariate analysis showed that PPIs uses was an independent prognostic factor affecting OS (HR=1.90, 95%CI: 1.27-2.85, P=0.002) and PFS (HR=1.73, 95%CI: 1.12-2.65, P=0.013). Meanwhile, subgroup analysis discovered that in the course of ICIs treatment of lung cancer patients, the median OS (3.2 months vs. 6.2 months) and median PFS (2.2 months vs. 3.8 months) in the PPIs group (n=64) were shorter than those in the Non-PPIs group (n=34) (χ ²=16.187, P<0.001; χ ²=5.106, P=0.020). Univariate analysis showed that PPIs uses was associated with OS (HR=2.97, 95%CI: 1.70-5.22, P<0.001) and PFS (HR=1.97, 95%CI: 1.09-3.55, P=0.025) in lung cancer patients treated with ICIs. Multivariate analysis showed that PPIs uses was an independent prognostic factor for OS (HR=3.38, 95%CI: 1.87-6.11, P<0.001) and PFS (HR=2.31, 95%CI: 1.22-4.38, P=0.010) in lung cancer patients treated with ICIs. Conclusion The use of PPIs reduces the effect of ICIs in the treatment of advanced solid tumor, especially in lung cancer. PPIs should be used cautiously in patients with advanced solid tumors treated with ICIs.

Key words: Proton pump inhibitors, Neoplasms, Prognosis, Immune checkpoint inhibitors

Liu Chaoxing, Yan Xuebing, Yang Mengxue, Tong Jiandong, Mao Haiyan. Effects of proton pump inhibitors on outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors[J]. Journal of International Oncology, 2022, 49(1): 26-32.

Figures/Tables 8

References 23

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组别	CR	PR	SD	PD	客观缓解	疾病控制
PPI组(n=73)	0(0)	18(24.7)	20(27.4)	35(47.9)	18(24.7)	38(52.0)
Non-PPI组(n=131)	0(0)	59(45.0)	40(30.5)	32(24.4)	59(45.0)	99(75.6)
χ²值					8.286	11.755
P值					0.004	0.001

变量	OS			PFS
变量	HR值	95%CI	P值	HR值	95%CI	P值
性别(男/女)	0.93	0.611.43	0.749	1.12	0.751.67	0.569
年龄(≤65岁/>65岁)	0.80	0.531.21	0.296	1.56	1.052.32	0.029
ECOG评分(01分/23分)	1.12	0.761.69	0.569	1.09	0.731.62	0.679
ICI治疗策略(ICI 单药/联合)	1.15	0.791.68	0.470	1.31	0.901.91	0.163
PPI(使用/未使用)	1.85	1.242.76	0.003	1.65	1.092.51	0.019

变量	OS			PFS
变量	HR值	95%CI	P值	HR值	95%CI	P值
性别(男/女)	0.84	0.521.26	0.468	0.95	0.601.50	0.839
年龄(≤65岁/>65岁)	1.44	0.882.33	0.145	1.61	1.002.58	0.050
ECOG评分(01分/23分)	1.22	0.801.84	0.352	1.25	0.821.92	0.300
ICI治疗策略(ICI 单药/联合)	1.18	0.791.75	0.424	1.31	0.881.96	0.185
PPI(使用/未使用)	1.90	1.272.85	0.002	1.73	1.122.65	0.013

变量	OS			PFS
变量	HR值	95%CI	P值	HR值	95%CI	P值
性别(男/女)	0.63	0.271.47	0.284	0.98	0.482.01	0.957
年龄(≤65岁/>65岁)	1.46	0.842.53	0.178	1.54	0.882.71	0.131
ECOG评分(01分/23分)	1.24	0.742.07	0.420	1.37	0.812.30	0.242
ICI治疗策略(ICI 单药/联合)	1.18	0.711.94	0.524	1.21	0.722.03	0.469
PPI(使用/未使用)	2.97	1.705.22	<0.001	1.97	1.093.55	0.025

变量	OS			PFS
变量	HR值	95%CI	P值	HR值	95%CI	P值
性别(男/女)	2.17	0.865.46	0.101	0.75	0.331.70	0.487
年龄(≤65岁/>65岁)	1.88	1.023.45	0.042	1.72	0.913.25	0.093
ECOG评分(01分/23分)	1.59	0.902.83	0.115	1.75	0.993.09	0.056
ICI治疗策略(ICI 单药/联合)	1.66	0.932.99	0.089	1.64	0.903.02	0.109
PPI(使用/未使用)	3.38	1.876.11	<0.001	2.31	1.224.38	0.010