Related Experiment Video
Updated: Jul 27, 2025
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
PD-1 inhibitors-based second-line therapy for metastatic gastric cancer
Miaomiao Gou1, Yong Zhang2, Zhikuan Wang1
1Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
Background:
Metastatic gastric cancer (MGC) patients with progression on first-line treatment still have poor outcomes on chemotherapy. The KEYNOTE-061 study demonstrated that pembrolizumab, a PD-1inhibitor, was not better than paclitaxel as second-line therapy for MGC. Herein, we explored the efficacy and safety of PD-1inhibitor based treatment for MGC patients in the second line.
Methods:
In this observational, retrospective study, we enrolled MGC patients treated with anti-PD-1 based therapy as second-line in our hospital. We primarily assessed the treatment's efficacy and safety. We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses.
Results:
We enrolled 129 patients with an objective response rate (ORR) of 16.3% and a disease control rate (DCR) of 79.1%. Patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents had ORR of 19.6% and higher DCR of 94.1%. The median progression-free survival (PFS) was 4.10 months, and the median overall survival (OS) was 7.60 months. In univariate analysis, patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents and with prior anti-PD-1 history were significantly associated with favorable PFS and OS. In the multivariate analysis, different combination therapy and prior anti-PD-1 history were independent prognosis biomarkers for PFS and OS. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 28 (21.7%) patients. Common adverse events (AEs) included fatigue, hyper/hypothyroidism, neutrophil decrease, anemia, skin reactions, proteinuria, and hypertension. We did not observe treatment-related deaths.
Conclusion:
Our current results indicated that PD-1-inhibitor and chemo-anti-angiogenic agents combination therapy and prior PD-1 treatment history might improve clinical activity for GC immunotherapy as second-line treatment with acceptable safety profiles. Further studies are needed to verify those outcomes for MGC in other centers.
Insights
For metastatic gastric cancer patients progressing on first-line therapy, PD-1 inhibitor combination treatments show promise as a second-line option. Combining PD-1 inhibitors with chemotherapy and anti-angiogenic agents improved outcomes and was well-tolerated.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Oncology
Background:
- Metastatic gastric cancer (MGC) patients often have poor outcomes with standard chemotherapy after first-line treatment failure.
- Pembrolizumab (a PD-1 inhibitor) did not show superiority over paclitaxel in the KEYNOTE-061 study for second-line MGC therapy.
- There is a need to explore alternative and effective second-line treatment strategies for MGC.
Purpose of the Study:
- To evaluate the efficacy and safety of PD-1 inhibitor-based treatments as a second-line therapy for MGC.
- To identify clinical features associated with favorable outcomes in MGC patients receiving second-line PD-1 inhibitor therapy.
Main Methods:
- Retrospective observational study of 129 MGC patients treated with anti-PD-1 based therapy as second-line treatment.
- Primary assessment of treatment efficacy (Objective Response Rate, Disease Control Rate) and safety (treatment-related adverse events).
- Univariate and multivariate analyses to correlate clinical features with progression-free survival (PFS) and overall survival (OS).
Main Results:
- The overall objective response rate (ORR) was 16.3% and disease control rate (DCR) was 79.1%.
- Combination therapy with PD-1 inhibitors, chemotherapy, and anti-angiogenic agents yielded a higher ORR (19.6%) and DCR (94.1%).
- Median PFS was 4.10 months and median OS was 7.60 months. Prior anti-PD-1 history and combination therapy were independent prognostic biomarkers for PFS and OS.
Conclusions:
- PD-1 inhibitor combined with chemotherapy and anti-angiogenic agents may improve clinical activity in second-line MGC treatment.
- Prior PD-1 treatment history appears to be a significant factor for improved outcomes.
- These combination therapies demonstrate acceptable safety profiles, warranting further investigation in larger, multi-center studies.
More Related Videos
10:28Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
Related Concept Videos
01:26Peptic Ulcer Disease IV: Management
The therapeutic approach involves ensuring adequate rest, implementing drug therapy, promoting smoking cessation, making dietary modifications, and emphasizing long-term follow-up care.
Pharmacological management
The prevailing therapy for peptic ulcers involves a combination of managing the patient's current...
01:13Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
01:20Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
01:27Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists