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Targeting the PD-1 pathway: a new hope for gastrointestinal cancers
Burak Bilgin1, Mehmet A N Sendur1, Muhammed Bülent Akıncı1
1a Yıldırım Beyazıt University , Faculty of Medicine, Department of Medical Oncology , Ankara , Turkey.
Background:
VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aim to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in published or reported recent studies.
Scope:
A literature search was made from PubMed and ASCO Annual Meeting abstracts by using the following search keywords: "nivolumab", "pembrolizumab", "avelumab", "GI cancers" "anti-PD1 therapy" and "anti-PD-L1 therapy". The last search was on 2 November 2016. The most important limitation of our review is that most of the data on anti-PD-1/PD-L1 therapies in GI cancers relies on phase 1 and 2 trials.
Findings:
Currently, there are two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PDL1 (atezolizumab) agents approved by FDA. After the treatment efficacy of immune checkpoint blockade was shown in melanoma, renal cell cancer and non-squamous lung cancer, trials which evaluate immune checkpoint blockade in GI cancers are ongoing. Early results of trials have been promising and encouraging for patients with advanced stage gastroesophageal cancer. According to early results of published trials, response to anti-PD1/PD-L1 agents appears to be associated with tumor PD-L1 levels. According to two recently published phase 2 trials, the clinical benefits of immune checkpoint blockade with both nivolumab and pembrolizumab were limited in patients with microsatellite instability (MSI) positive advanced colorectal cancer. However, several phase 2/3 trials are still ongoing.
Conclusion:
Both pembrolizumab and nivolumab show promising efficacy with acceptable safety data in published trials in GI cancers, especially in refractory MSI positive metastatic colorectal cancer.
Insights
Immune checkpoint inhibitors like anti-PD-1/PD-L1 therapies show promise for gastrointestinal (GI) cancers. While effective in some advanced GI cancers, particularly MSI-positive colorectal cancer, further trials are ongoing.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Cancers
Background:
- Targeted therapies (VEGF, HER2, EGFR) have limited success in gastric, esophageal, and colorectal cancers.
- Immunotherapy, specifically immune checkpoint inhibitors, presents a promising avenue for improving treatment outcomes.
- Gastrointestinal (GI) cancers remain a significant challenge despite current therapeutic strategies.
Purpose of the Study:
- To review the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers.
- To discuss recent studies on immunotherapy for gastric, esophageal, and colorectal cancers.
- To evaluate the potential of immune checkpoint blockade in advanced GI malignancies.
Main Methods:
- Literature search of PubMed and ASCO Annual Meeting abstracts.
- Keywords included specific anti-PD-1/PD-L1 agents and GI cancer types.
- Data primarily sourced from Phase 1 and 2 clinical trials up to November 2016.
Main Results:
- Anti-PD-1 (nivolumab, pembrolizumab) and anti-PD-L1 (atezolizumab) agents are FDA-approved for other cancers.
- Early trials in advanced gastroesophageal cancer show promising results for immune checkpoint blockade.
- Response to anti-PD1/PD-L1 agents correlates with tumor PD-L1 levels.
- Limited clinical benefit observed in MSI-positive advanced colorectal cancer with nivolumab and pembrolizumab.
Conclusions:
- Pembrolizumab and nivolumab demonstrate promising efficacy and acceptable safety in GI cancers.
- These agents are particularly effective in refractory, microsatellite instability- (MSI) positive metastatic colorectal cancer.
- Ongoing Phase 2/3 trials are crucial for further understanding and application of these therapies.
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