Abstract
Objective
Programmed death-1 (PD-1) inhibitors combined with chemotherapy show certain clinical benefits in advanced gastric cancer patients, but more evidence is still needed. The present study aimed to investigate the efficacy and safety of PD-1 inhibitors combined with chemotherapy in these patients.
Methods
Forty-three patients with advanced gastric cancer receiving PD-1 inhibitors (including camrelizumab, sintilimab, and tislelizumab, 200 mg every 3 weeks) combined with chemotherapy were retrospectively enrolled. Data on treatment response, progression-free survival (PFS), and adverse reactions were collected.
Results
There were 1 (2.3%), 9 (20.9%), 32 (74.4%), and 1 (2.3%) patient who achieved complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate and disease control rate were 23.3% and 97.7%. The 1- and 2-year cumulative PFS rates were 63.3% and 19.8%. The median PFS (95% confidence interval) was 13.5 (10.7–16.3) months. Higher Eastern Cooperative Oncology Group performance status score (per score) [hazard ratio (HR) = 5.404, P = 0.047] and higher maximum diameter of the lesion (per cm) (HR = 1.860, P = 0.048) independently predicted shorter PFS. The adverse reactions included hemoglobin decreased (76.7%; grade 3: 16.3%), white blood cells decreased (74.4%; grade 3: 7.0%), blood platelet decreased (25.6%; grade 3: 2.3%), white blood cells increased (9.3%; grade 3: none), and reactive cutaneous capillary endothelial proliferation (23.3%; grade 3: 2.3%).
Conclusion
PD-1 inhibitors combined with chemotherapy may be an optional regimen for patients with advanced gastric cancer. However, the retrospective design and small sample size may limit the generalizability and robustness of our findings.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12876-025-04207-0.
Keywords: Programmed death-1 inhibitors combined with chemotherapy, Advanced gastric cancer, Treatment response, Progression-free survival, Adverse reactions
Introduction
Gastric cancer is a highly aggressive and heterogeneous malignant tumor that seriously threatens human health [1, 2]. The prognosis of patients with advanced gastric cancer is very poor, with a median overall survival (OS) of only 10.0-15.7 months [3, 4]. Chemotherapy is the cornerstone for the treatment of advanced gastric cancer, but the efficacy of chemotherapy alone is unsatisfactory [5, 6]. Notably, immunotherapy activates host immune system to eliminate tumor cells, which has led to some progression in the treatment of patients with advanced gastric cancer [7, 8].
Programmed death-1 (PD-1) inhibitors, which play a key role in cancer immunotherapy, reactivate T-cell function to suppress tumor growth and immune escape [9–12]. Previous studies have shown the favorable efficacy and manageable toxicity of PD-1 inhibitors combined with chemotherapy in patients with advanced gastric cancer [13–16]. For example, the randomized, controlled ATTRACTION-4 trial revealed that nivolumab combined with chemotherapy improved progression-free survival (PFS) compared with placebo combined with chemotherapy in patients with advanced gastric cancer [13]. The KEYNOTE-859 study revealed that, compared to placebo plus chemotherapy, pembrolizumab combined with chemotherapy increased OS with tolerable toxicity in patients with advanced gastric cancer [14]. Moreover, some previous real-world studies also showed that patients with advanced gastric cancer could benefit from PD-1 inhibitors combined with chemotherapy [17, 18]. However, more studies are needed to provide additional clinical evidence.
Therefore, the purpose of this study was to investigate the treatment response, survival outcome, and adverse reactions of patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy.
Materials and methods
Patients
This retrospective, observational study included 43 patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy.
Patients were consecutively enrolled from May 2021 to March 2024. The inclusion criteria were as follows: (1) patients who were diagnosed with gastric cancer via a pathological method; (2) patients who had advanced disease: with tumor-node-metastasis (TNM) stage III/IV; (3) patients who were aged more than 18 years; (4) patients who received PD-1 inhibitors; and (5) patients whose treatment response data was available. Patients who were HER2 positive (+ + or +++) measured by immunohistochemistry (IHC) + fluorescence in situ hybridization ratio (FISH), had Eastern Cooperative Oncology Group performance status (ECOG PS) scores greater than 2, or other primary malignancies were excluded. This retrospective study was approved by the Institutional Review Board of Anqing 116 Hospital (Approval no. 2023-HYNL-037). All procedures were followed in accordance with the Declaration of Helsinki under the Ethics approval. Each participant signed the informed consent form.
Treatment
Patients in the present study received PD-1 inhibitors combined with chemotherapy. PD-1 inhibitors, including camrelizumab, sintilimab, and tislelizumab, were used in this study. Camrelizumab, sintilimab, and tislelizumab were administrated at 200 mg every 3 weeks until disease progression or intolerance. Chemotherapy drugs, including fluorouracil, tegafur, S-1, capecitabine, raltitrexed, cisplatin, nedaplatin, oxaliplatin, docetaxel, albumin-bound paclitaxel, paclitaxel, and irinotecan, were used in this study. This study did not interfere with the treatment of patients. Treatment selection was based on physician judgment and patient preference, and the physician judgment was in accordance with the Chinese Society of Clinical Oncology (CSCO) guidelines [19, 20].
Data collection
The data extracted from the electronic medical record database of Anqing 116 Hospital was collected from January 2024 to May 2024. Clinical features, including age, gender, smoke, hypertension, history of gastrectomy, history of radiotherapy, ECOG PS score, histological type, TNM stage, differentiation, and status of metastasis, were retrieved. In addition, baseline laboratory indexes, including blood tumor markers, blood routine examinations, and blood biochemical indexes, were also collected.
Observed indicators
Clinical response information was gathered and evaluated via CT or MRI every 2 months after treatment as per the iRECIST guideline [21]. Patients initially assessed as PD were designated unconfirmed progressive disease, and they were confirmed as either pseudoprogression or confirmed progressive disease in the next assessment (Patients continued to receive treatment during the period). In our study, there were 3 patients with pseudoprogression, and these patients continued to receive the treatment and follow-up. No patient continued treatment when diagnosed as confirmed progressive disease. The median number of actual scans per patient was 3, and 22 (51.5%) patients deviated from the schedule (2 months ± 1 week). The median follow-up time of the patients was 5.4 months. The observed indicators included the objective response rate (ORR), disease control rate (DCR), and cumulative PFS rate. Adverse reactions were collected and evaluated via the Common Terminology Criteria for Adverse Events (v.5.0), which was accessible at https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf).
Statistics
Statistical analysis was carried out by SPSS v.29.0 (IBM, USA). Continuous variables were presented as median with interquartile range (IQR). The counting variables were presented as numbers with percentages. Patients lost to follow-up (n = 21) were censored at their last known progression-free date in the Kaplan-Meier analysis. Given high loss to follow-up, a sensitivity analysis was performed by worst-case scenarios analysis. The Kaplan-Meier method was performed for estimating accumulating PFS rates, and the Log-rank test was applied to compare them. The multivariate Cox regression model was performed to assess the associations of clinical features with PFS. A post hoc statistical power analysis was conducted using One-Sample Log-rank Test module of PASS software (version 15.0.5, NCSS, LLC). A P value < 0.05 indicated significance.
Results
Clinical features and laboratory indexes
The median (IQR) age of the 43 patients was 71.0 (61.0–77.0) years. Among these patients, 7 (16.3%) were females and 36 (83.7%) were males. In terms of TNM stage, 21 (48.8%) patients were in TNM stage III and 22 (51.2%) were in TNM stage IV. There were 32 (74.4%) patients with metastasis. More specific information is shown in Table 1.
Table 1.
Clinical characteristics of patients with advanced gastric cancer
| Characteristics | Patients (N = 43) |
|---|---|
| Age (years), median (IQR) | 71.0 (61.0–77.0) |
| Gender, n (%) | |
| Female | 7 (16.3) |
| Male | 36 (83.7) |
| Smoke, n (%) | |
| Never | 25 (58.1) |
| Former or current | 18 (41.9) |
| Hypertension, n (%) | |
| No | 29 (67.4) |
| Yes | 14 (32.6) |
| History of gastrectomy, n (%) | |
| No | 24 (55.8) |
| Yes | 19 (44.2) |
| History of radiotherapy, n (%) | |
| No | 33 (76.7) |
| Yes | 10 (23.3) |
| ECOG PS score, n (%) | |
| 0 | 2 (4.7) |
| 1 | 35 (81.4) |
| 2 | 6 (14.0) |
| Histological type, n (%) | |
| Adenocarcinoma | 39 (90.7) |
| Squamous carcinoma, signet ring cell carcinoma, or unknown | 4 (9.3) |
| TNM stage, n (%) | |
| III | 21 (48.8) |
| IV | 22 (51.2) |
| Maximum diameter of the lesion (cm), median (IQR) | 2.3 (1.2–3.2) |
| Differentiation, n (%) | |
| Well-to-moderately or moderately | 4 (9.3) |
| Moderately-to-poorly or poorly | 22 (51.2) |
| Undifferentiated or unable to assess | 17 (39.5) |
| Metastasis, n (%) | |
| No | 11 (25.6) |
| Yes | 32 (74.4) |
| Lymphatic metastasis, n (%) | |
| No | 29 (67.4) |
| Yes | 14 (32.6) |
| Peritoneal metastasis, n (%) | |
| No | 35 (81.4) |
| Yes | 8 (18.6) |
| Liver metastasis, n (%) | |
| No | 31 (72.1) |
| Yes | 12 (27.9) |
| Bone metastasis, n (%) | |
| No | 40 (93.0) |
| Yes | 3 (7.0) |
The continuous variables were presented as median with interquartile range (IQR). The counting variables were presented as numbers with percentages
IQR Interquartile range, ECOG PS Eastern cooperative oncology group performance status, TNM Tumor-node-metastasis
The laboratory indexes of patients with advanced gastric cancer were collected. Regarding blood tumor markers, the median (IQR) values of carcinoembryonic antigen, carbohydrate antigen (CA) 125, CA 199, and alpha-fetoprotein were 4.3 (1.8–24.8) ng/mL, 23.0 (12.5–44.9) U/mL, 13.4 (5.0-62.9) U/mL, and 2.8 (2.0-5.2) ng/mL, respectively. Other detailed laboratory indexes, including blood routine examinations and blood biochemical indexes, are listed in Table 2.
Table 2.
Laboratory indexes of patients with advanced gastric cancer
| Items | Patients (N = 43) |
|---|---|
| Blood tumor markers | |
| CEA (ng/mL), median (IQR) | 4.3 (1.8–24.8) |
| CA 125 (U/mL), median (IQR) | 23.0 (12.5–44.9) |
| CA 199 (U/mL), median (IQR) | 13.4 (5.0-62.9) |
| AFP (ng/mL), median (IQR) | 2.8 (2.0-5.2) |
| Blood routine examinations | |
| WBC (10^9/L), median (IQR) | 4.9 (3.7–6.7) |
| RBC (10^12/L), median (IQR) | 3.6 (3.3-4.0) |
| Hb (g/L), median (IQR) | 104.0 (96.0-124.5) |
| PLT (10^9/L), median (IQR) | 208.5 (152.8-272.8) |
| Blood biochemical indexes | |
| ALP (IU/L), median (IQR) | 79.0 (64.5-105.3) |
| ALT (IU/L), median (IQR) | 14.0 (11.0-25.5) |
| AST (IU/L), median (IQR) | 23.5 (20.0-28.5) |
| ALB (g/L), median (IQR) | 39.4 (35.3–42.6) |
| Cr (µmol/L), median (IQR) | 69.5 (59.5–82.3) |
| UA (µmol/L), median (IQR) | 276.0 (229.3-325.5) |
The laboratory indexes were presented as median with interquartile range (IQR). The counting variables were presented as numbers with percentages
IQR Interquartile range, CEA Carcinoembryonic antigen, CA Carbohydrate antigen, AFP Alpha-fetoprotein, WBC White blood cell count, RBC Red blood cell count, Hb hemoglobin, PLT Platelet count, ALP Alkaline phosphatase, ALT Alanine aminotransferase, AST Aspartate aminotransferase, ALB Albumin, Cr Creatinine, UA Uric acid
Treatment response
One (2.3%) patient achieved complete response (CR). Meanwhile, there were 9 (20.9%) patients who had partial response (PR), 32 (74.4%) patients who had stable disease (SD), and 1 (2.3%) patient who achieved progressive disease (PD). Patients achieved an ORR of 23.3% and a DCR of 97.7%, respectively (Table 3).
Table 3.
Clinical response
| Items | Patients (N = 43) |
|---|---|
| Best response, n (%) | |
| CR | 1 (2.3) |
| PR | 9 (20.9) |
| SD | 32 (74.4) |
| PD | 1 (2.3) |
| ORR, n (%) | 10 (23.3) |
| DCR, n (%) | 42 (97.7) |
The clinical responses were presented as numbers with percentages
CR Complete response, PR Partial response, SD Stable disease, PD Progressive disease, ORR Objective response rate, DCR Disease control rate
PFS and related factors
The 1-year and 2-year cumulative PFS rates were 63.3% and 19.8%, respectively. The median (95% confidence interval (CI)) PFS was 13.5 (10.7–16.3) months (Fig. 1). Lower ECOG PS score (P = 0.004) and adenocarcinoma status (P = 0.043) were related to prolonged PFS (Fig. 2A-B). However, there was no association of TNM stage (P = 0.253), the degree of differentiation (P = 0.639), or metastasis (P = 0.719) with PFS (Fig. 2C-E). Moreover, the multivariate analysis revealed that higher ECOG PS score (per score) [hazard ratio (HR) = 5.404, P = 0.047] and maximum diameter of the lesion (per cm) (HR = 1.860, P = 0.048) were independently associated with reduced PFS (Table 4).
Fig. 1.
Accumulating PFS rates of patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy
Fig. 2.
Association of clinical features with PFS in patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy. The association of ECOG PS score (A), histological type (B), TNM stage (C), differentiation (D), and metastasis (E) with PFS in patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy
Table 4.
The multivariate Cox regression analysis on PFS
| Characteristics | P value | HR | 95% CI | |
|---|---|---|---|---|
| Lower | Upper | |||
| Hypertension (yes vs. no) | 0.747 | 1.396 | 0.184 | 10.559 |
| History of gastrectomy (yes vs. no) | 0.431 | 0.482 | 0.079 | 2.955 |
| History of radiotherapy (yes vs. no) | 0.062 | 0.085 | 0.006 | 1.135 |
| ECOG PS score (per score) | 0.047 | 5.404 | 1.024 | 28.522 |
| Histological type (squamous carcinoma, signet ring cell carcinoma, or unknown vs. adenocarcinoma) | 0.945 | 1.354 | < 0.001 | 7033.195 |
| Maximum diameter of the lesion (per cm) | 0.048 | 1.860 | 1.005 | 3.444 |
| Metastasis (yes vs. no) | 0.486 | 0.385 | 0.026 | 5.663 |
| Treatment line (second line vs. first line) | 0.415 | 2.461 | 0.282 | 21.492 |
| Chemotherapy regimens | ||||
| Platinum (reference) | (-) | 1.000 | (-) | (-) |
| Taxanes vs. reference | 0.824 | 2.626 | 0.001 | 13017.647 |
| Platinum + Taxanes vs. reference | 0.281 | 3.838 | 0.334 | 44.148 |
| Others vs. reference | 0.297 | 3.674 | 0.318 | 42.381 |
The multivariate Cox regression analyses was performed by enter method
PFS Progression-free survival, HR Hazard ratio, CI Confidence interval, ECOG PS Eastern Cooperative Oncology Group performance status
Subgroup analyses for PFS
The treatment information (Supplementary Table 1) and lost-to-follow-up information (Supplementary Table 2) of patients are exhibited. Subgroup analyses revealed that PFS did not vary among patients receiving different PD-1 inhibitors (P = 0.754) or different chemotherapy regimens (P = 0.573) (Supplementary Fig. 1A-B). Moreover, PFS was not affected by the reasons of lost follow-up, either (P = 0.491) (Supplementary Fig. 2).
Sensitivity analysis
Sensitivity analysis by worst-case scenarios analysis disclosed that the median (95% CI) PFS was 7.3 (3.2–11.5) months in patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy (Supplementary Fig. 3).
Adverse reactions
There were 33 (76.7%) patients with hemoglobin decreased, including 7 (16.3%) patients of grade III. A total of 32 (74.4%) patients experienced white blood cells decreased, of which 3 (7.0%) were grade III. Blood platelet decreased occurred in 11 (25.6%) patients, and there was 1 (2.3%) patient of grade III. Four (9.3%) patients experienced white blood cells increased, and none of them was grade III. Moreover, there were 10 (23.3%) patients with reactive cutaneous capillary endothelial proliferation (RCCEP), of whom 1 (2.3%) patient was grade III (Table 5).
Table 5.
Adverse reactions
| Reactions, n (%) | Any | Grade I | Grade II | Grade III |
|---|---|---|---|---|
| Hemoglobin decreased | 33 (76.7) | 12 (27.9) | 14 (32.6) | 7 (16.3) |
| White blood cells decreased | 32 (74.4) | 11 (25.6) | 18 (41.9) | 3 (7.0) |
| Blood platelet decreased | 11 (25.6) | 8 (18.6) | 2 (4.7) | 1 (2.3) |
| White blood cells increased | 4 (9.3) | 3 (7.0) | 1 (2.3) | 0 (0.0) |
| RCCEP | 10 (23.3) | 8 (18.6) | 1 (2.3) | 1 (2.3) |
The adverse reactions were presented as numbers with percentages
RCCEP Reactive cutaneous capillary endothelial proliferation
Discussion
A prior study showed that the ORR was 66.0% and the DCR was 91.0% in patients with advanced gastric cancer who were treated with nivolumab plus chemotherapy [22]. Another study found that patients with advanced gastric cancer receiving camrelizumab combined with chemotherapy achieved an ORR and a DCR of 62.2% and 82.2%, respectively [23]. In our study, the ORR and DCR of patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy were 23.3% and 97.7%, respectively. The ORR was lower and the DCR was similar in our study versus those in previous studies [22, 23]. This might be attributed to the following reasons: (1) The patients included in our study had a mean (IQR) age of 71.0 (61.0–77.0) years. These patients might not be able to receive a complete treatment cycle; therefore, the ORR of our study was relatively low. (2) A large proportion of patients (74.4%) had metastasis, which might influence the results. (3) It was hypothesized that the programmed cell death ligand 1 status and microsatellite instability status of patients might also lead to the low ORR; however, our study did not collect this information. Notably, in our study, the DCR of 97.7% was driven by a high rate of SD (74.4%). Meanwhile, the cumulative PFS rates showed that a major proportion of patients had no disease progression over 12 months. This finding indicated that SD might have a durable effect rather than a transient effect. Moreover, for elderly patients with advanced cancers, a stable disease condition might be a more practical treatment goal than tumor shrinkage [24]. However, the above results of our study might not be sufficiently generalizable and robust due to the retrospective design and small sample size, which required further verification.
A study suggested that the median PFS was 10.03 months in patients with untreated, HER2-negative, advanced gastric cancer who underwent camrelizumab plus chemotherapy [25]. In another study, the median PFS was 10.45 months in patients with advanced gastric cancer who received nivolumab plus chemotherapy [13]. The median PFS of our study was 13.5 months in patients with advanced gastric cancer who received PD-1 inhibitors combined with chemotherapy. The PFS of our study was higher than the results from the above studies [25], which might be because: Although ORR was only 23.3% in our study, the vast majority of patients had SD (74.4%), which indicated that these patients’ conditions were under control, thus prolonging PFS. Our study also found that lower ECOG PS score and adenocarcinoma were linked with prolonged PFS in these patients. The possible reasons would be as follows: (1) Patients with lower ECOG PS scores might have an increased ability to tolerate treatment, leading to better prognoses [13, 26]. (2) In our study, there were 39 patients with adenocarcinoma and 4 patients with squamous carcinoma, signet ring cell carcinoma, or unknown histological types. These four patients might represent outliers due to the small subgroup size, thus influencing the results. However, it was only a speculation and required further verification. Moreover, our study conducted multivariate analysis. The results showed that higher ECOG PS score and maximum diameter of the lesion were independently associated with shorter PFS, while histological type was not an independent factor linked with PFS. The independent association of maximum diameter of the lesion with PFS might because: Higher maximum diameter of the lesion represented increased tumor burden, thus reflecting disease progression [21]. Similarly, it was necessary to emphasize that all results still required further verification due to the retrospective design and the small sample size of our study.
Although PD-1 inhibitors combined with chemotherapy have exhibited some clinical benefits for advanced gastric cancer, their related adverse reactions should not be ignored [16, 22, 27]. A previous study showed that the most frequent adverse reactions were peripheral sensory neuropathy, decreased appetite, nausea, platelet count decreased, and neutrophil count decreased in patients with advanced gastric cancer receiving pembrolizumab plus S-1 and oxaliplatin [16]. Another study disclosed that the most common adverse reactions included nausea, platelet count decreased, white blood cell count decreased, and neutrophil count decreased in patients with advanced gastric cancer who received nivolumab plus chemotherapy [9]. The adverse reactions in our study were partly similar to those of previous studies [16, 22]. In our study, the adverse reactions were hemoglobin decreased (76.7%), white blood cells decreased (74.4%), blood platelet decreased (25.6%) and white blood cells increased (9.3%). The grade 3 adverse reactions included hemoglobin decreased (16.3%), white blood cells decreased (7.0%), and white blood cells increased (2.3%). Regarding immune-related adverse reactions, 10 (23.3%) patients experienced RCCEP, and 1 (2.3%) patient was grade III. Moreover, there was no new adverse reaction. These findings revealed that the safety profile of PD-1 inhibitors combined with chemotherapy was acceptable in patients with advanced gastric cancer. Nevertheless, more prospective studies with large sample sizes were needed for further verification.
Notably, in our study, the proportion of patients lost to follow-up was high. In detail, a total of 21 patients suspended medication, abandoned treatment, or could not be contacted during the follow-up period. The detailed explanations were as follows: (1) The drugs used in our study were expensive and not covered by medical insurance at the time, which placed a heavy financial burden on patients’ families. Meanwhile, since these patients (n = 9) were already in the advanced stage and most of them were older, their families chose to give up treatment eventually. (2) Due to the coronavirus disease 2019 (COVID-19) pandemic, some participants (n = 7) were not followed up at that time and could not be contacted later.
It was necessary to clarify, in our study, the ORR was relatively low (23.3%), but the median PFS was relatively favorable (13.5 months), which could be explained by the following reason: Although the ORR was relatively low, the SD was high (74.4%), indicating that most patients had no disease progression.
Our study had several limitations: (1) The sample size of our study was small (N = 43), which limited the statistical power of our findings. For example, the CIs around the efficacy estimates (ORR and PFS) might be wide, and the results might not be generalizable to a broader population of patients with advanced gastric cancer. A post hoc statistical power analysis based on a previous study was performed [22], revealing that our study achieved a statistical power of 81.4%. However, a larger sample size was still required for further verification in future studies. (2) The results of subgroup analyses might be underpowered and potentially unreliable due to the small number in the subgroups. (3) Our study was a real-world study that provided evidence on the feasibility of PD-1 inhibitors combined with chemotherapy for advanced gastric cancer. However, the lack of a control group made it difficult to definitively attribute the therapeutic efficacy entirely to the addition of PD-1 inhibitors. Although our study compared our results to some historical data from previous studies, the differences between studies (such as patient selection, baseline characteristics, treatment eras, and study methodologies) caused the comparative results to be indirect and biased. Thus, future studies should include a control group to compare the efficacy and safety of PD-1 inhibitors combined with chemotherapy versus chemotherapy alone in patients with advanced gastric cancer. (4) Our study was a retrospective study, which was inherently prone to selection bias, information bias, and some confounding variables that might not have been adequately controlled for. Meanwhile, the lack of randomization and a pre-defined protocol might impact the validity of the results. Thus, more prospective studies were needed for further verification. (5) Due to the constraint of a retrospective study design, some critical biomarker data for gastric cancer (such as programmed death ligand-1status or microsatellite instability status) were not retrieved. The absence of these critical biomarkers limited our study’s ability to identify patient subgroups most likely to benefit from treatment and reduced the comparability of our findings with those of other studies. (6) Moreover, due to some reasons (such as COVID-19 and patients giving up treatment), the rate of patients who were lost to follow-up was high, potentially causing overestimation of median PFS. (7) Given the limitation of retrospective design, some information on treatment delays, dose reductions, or therapy discontinuations related to adverse reactions could not be retrieved. This might limit the clinical utility of the safety findings and reduce confidence in the safety profile assessment of the treatment combination. Moreover, the collection and grading of adverse reactions might be subject to variability and underreporting compared to a prospective study with systematic monitoring, which created uncertainty about the true safety profile and led to underestimation of treatment-related toxicities. (8) The median follow-up time of our study was relatively shorter (5.4 months), and a longer follow-up time was required to fully assess the long-term efficacy of PD-1 inhibitors combined with chemotherapy in patients with advanced gastric cancer. (9) Our study was conducted at a single institution in China. Thus, the findings might not be directly generalizable to other ethnic populations or healthcare settings with differences in patient characteristics, treatment practices, or access to care. (10) The lack of treatment standardization might also be a limitation that affected our results. Overall, the results, particularly the ORR and PFS results, needed to be interpreted with caution due to these limitations.
Conclusions
In conclusion, PD-1 inhibitors combined with chemotherapy may be an alternative choice for patients with advanced gastric cancer. However, the efficacy and safety of the PD-1 inhibitors combined with chemotherapy regimen may be overestimated due to the constraints of a retrospective study design. Thus, this treatment modality still requires confirmation in more clinical trials.
Supplementary Information
Acknowledgements
Not applicable.
Authors’ contributions
Xiaofei Cheng contributed to the conception of the study. Yang Zhang, Xingyuan Li, Zhenning Xu and Yaolin Chen contributed to the data acquisition. Xiaofei Cheng, Yang Zhang and Xingyuan Li contributed to the analysis of data. Xiaofei Cheng, Yang Zhang, Xingyuan Li, Zhenning Xu and Yaolin Chen wrote and revised the manuscript. All authors read and approved the final manuscript.
Funding
No funding was received.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by the Ethics Review Board of the Department of Oncology, Anqing 116 Hospital. All procedures were followed in accordance with the Declaration of Helsinki under the Ethics approval. Each participant signed the informed consent.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.