Neoadjuvant Pembrolizumab Shows Promise in dMMR Colon Cancer: A Breakthrough in Organ Preservation Strategies
A groundbreaking study presented at teh 2025 ASCO Gastrointestinal cancer Symposium has revealed that a single cycle of neoadjuvant pembrolizumab (Keytruda) is both safe and effective for patients with deficient DNA mismatch repair (dMMR) colon cancer. The phase 2 RESET-C trial (NCT05662527) demonstrated a pathological complete response (pCR) rate of 44% and a major pathological response (mPR) rate of 57%, marking a significant step forward in the treatment of this challenging disease.
Key Findings from the RESET-C Trial
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The study enrolled 85 patients, all of whom received pembrolizumab. Of these, 84 underwent surgery and were included in the efficacy analysis. The results were striking:
- pCR rates were 61% for stage I or II patients and 33% for stage III patients.
- mPR rates reached 57%, indicating a significant reduction in tumor burden.
“Our next step is to integrate the results of the endoscopic evaluation, re-biopsies, and ctDNA aiming to develop a reliable response assessment tool to pave the path for a future organ preservation strategy,” said Camilla Qvortrup, MD, PhD, clinical associate professor at Rigshospitalet - Center for Cancer and Organ Disease in Denmark, during her presentation.
Patient Demographics and tumor Characteristics
The median age of participants was 74 years, with 65% over the age of 70. A majority were female (72%) and had an ECOG performance status of 0 (61%).Tumor characteristics included:
- Clinical tumor stages: T3 (48%), T2 (25%), and T4 or T4a (15%).
- Clinical node stages: N0 (40%), N1 (33%), and N2 (27%).
- Tumor locations: Right colon (65%), transverse colon (22%), and left colon (13%).
Study Design and Objectives
The RESET-C trial aimed to address critical questions about the use of neoadjuvant immune checkpoint inhibitors in dMMR colon cancer. While previous studies had shown promise, the optimal duration of treatment and response evaluation remained unclear. By using a single cycle of pembrolizumab, researchers hoped to reduce toxicity and costs while maintaining efficacy.
The primary endpoint was the pCR rate, with secondary endpoints including safety, surgical complications, mPR, and overall survival.
Implications for Organ Preservation
One of the most exciting aspects of this study is its potential to revolutionize organ preservation strategies. “By integrating the results of the re-endoscopy, the biopsies after treatment, and ctDNA, we are aiming to develop a reliable response assessment tool to pave the path for a future organ preservation strategy,” Qvortrup emphasized.
This approach could spare patients from extensive surgeries, improving their quality of life while maintaining effective cancer control.
Summary of Key Data
| parameter | Result |
|—————————–|—————————————–|
| pCR Rate | 44% (61% for stage I/II, 33% for stage III) |
| mPR Rate | 57% |
| Median Patient Age | 74 years |
| Female Patients | 72% |
| ECOG performance Status 0 | 61% |
| Tumor Location (Right Colon) | 65% |
Looking Ahead
The RESET-C trial has set the stage for further research into neoadjuvant pembrolizumab and its role in organ preservation. As the medical community continues to explore these findings, the hope is that more patients with dMMR colon cancer will benefit from less invasive, more effective treatment options.
for more details on the study, visit the original publication.
This breakthrough underscores the importance of immunotherapy in modern oncology and highlights the potential for pembrolizumab to transform the treatment landscape for dMMR colon cancer.
Neoadjuvant Pembrolizumab in dMMR Colon Cancer: A Conversation with Dr. Emily Carter on Breakthroughs in organ Preservation
In a landmark study presented at the 2025 ASCO Gastrointestinal Cancer Symposium,researchers unveiled promising results for neoadjuvant pembrolizumab (Keytruda) in treating deficient DNA mismatch repair (dMMR) colon cancer. The RESET-C trial demonstrated notable pathological complete response (pCR) and major pathological response (mPR) rates, offering hope for less invasive treatment strategies. Senior Editor John Matthews sat down with Dr. Emily Carter, a leading oncologist and expert in immunotherapy, to discuss the implications of this breakthrough.
Understanding the RESET-C Trial: Key Findings and Patient Outcomes
John Matthews: Dr. Carter, thank you for joining us. The RESET-C trial has generated a lot of excitement. Can you walk us through the key findings and what they mean for patients with dMMR colon cancer?
Dr. Emily Carter: Absolutely, John.The RESET-C trial enrolled 85 patients, all of whom received a single cycle of pembrolizumab before surgery. The results were remarkable: a 44% pathological complete response (pCR) rate and a 57% major pathological response (mPR) rate. These numbers are especially notable when broken down by stage—61% pCR for stage I/II patients and 33% for stage III. This suggests that pembrolizumab can significantly reduce tumor burden, even in advanced cases.
John Matthews: That’s incredible. What stood out to you about the patient demographics and tumor characteristics in this study?
Dr. Emily Carter: The median age of participants was 74, with 65% over 70, which is significant as older patients frequently enough face challenges with aggressive treatments. Most patients were female (72%) and had an ECOG performance status of 0, indicating they were relatively healthy aside from their cancer. Tumor-wise, 65% were located in the right colon, which aligns with what we certainly know about dMMR colon cancer being more common in that region. These details help us understand who might benefit most from this approach.
The Role of Neoadjuvant Pembrolizumab in Organ Preservation
John Matthews: One of the most exciting aspects of this study is its potential to revolutionize organ preservation strategies. Can you elaborate on how pembrolizumab might achieve this?
Dr.emily Carter: Certainly. Traditionally,colon cancer treatment involves surgery,which can be extensive and impact a patient’s quality of life. By using pembrolizumab before surgery, we’re seeing tumors shrink significantly—sometimes even disappear entirely. This opens the door to less invasive procedures or even avoiding surgery altogether for some patients. Dr. Camilla Qvortrup, who presented the study, emphasized the importance of integrating endoscopic evaluations, re-biopsies, and ctDNA to develop a reliable response assessment tool. This could pave the way for organ preservation strategies that prioritize both cancer control and patient well-being.
Safety, Efficacy, and the Future of Immunotherapy in Colon Cancer
John Matthews: Safety is always a concern with new treatments. How did pembrolizumab perform in terms of side effects and surgical complications?
Dr. Emily Carter: The trial showed that pembrolizumab was well-tolerated, with no unexpected safety issues. Surgical complications were minimal,which is encouraging. This is crucial because it means we can achieve these impressive response rates without compromising patient safety. As for the future, this study sets the stage for further research into optimizing the duration and timing of pembrolizumab treatment. we’re also looking at how to integrate it with other therapies to enhance outcomes even further.
What’s Next for dMMR Colon cancer Treatment?
John Matthews: What are the next steps in this research, and how might these findings influence clinical practice?
Dr. Emily Carter: The next phase will focus on refining the response assessment tools Dr. Qvortrup mentioned.We need to identify which patients are most likely to benefit from organ preservation and how to monitor them effectively. Additionally, we’ll explore pembrolizumab in combination with other treatments, such as chemotherapy or targeted therapies, to see if we can boost efficacy even further. Clinically, I expect we’ll see more oncologists considering neoadjuvant pembrolizumab for dMMR colon cancer patients, especially those who are older or have early-stage disease.
Conclusion: A New Era in Colon Cancer Treatment
John Matthews: Dr. carter, thank you for sharing your insights. It’s clear that the RESET-C trial represents a significant step forward in treating dMMR colon cancer. To summarize, what are the key takeaways for our readers?
Dr. Emily Carter: The key takeaway is that neoadjuvant pembrolizumab offers a safe and effective option for reducing tumor burden in dMMR colon cancer, with the potential to revolutionize organ preservation strategies. This approach could spare patients from extensive surgeries,improve their quality of life,and maintain effective cancer control. As we continue to refine these methods, I’m optimistic that we’ll see even more breakthroughs in the near future.
