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Pathological Tumor Response Following Immune Checkpoint Blockade for Deficient Mismatch Repair Advanced Colorectal
Kaysia Ludford1, Romain Cohen2, Magali Svrcek3
1Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
Immune checkpoint inhibition (CPI) for metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) demonstrates high clinical activity that appears durable, but the impact of CPI on pathological tumor response is unknown. In this retrospective analysis, our objective was to assess pathological response and clinical outcomes in dMMR mCRC patients treated with CPI prior to surgical resection of primary and/or metastatic tumor. Among 121 advanced dMMR mCRC patients treated with CPI at 2 institutions between November 2016 and December 2018, 14 underwent surgery. Pathologic complete response was noted in the resected specimens of 13 patients despite the presence of residual tumor on preoperative imaging in 12 of those patients. With median follow-up of 9 months, no patients have had disease relapse or progression. For this small retrospective study, the data suggest that residual radiographic tumor may not require systematic resection following response to anti-PD1-based therapy. However, larger prospective studies are warranted.
Insights
Immune checkpoint inhibition (CPI) shows durable activity in deficient mismatch repair metastatic colorectal cancer (dMMR mCRC). Pathological complete response was observed in most surgically resected tumors after CPI, suggesting potential for non-operative management.
Area of Science:
- Oncology
- Immunotherapy
- Colorectal Cancer Research
Background:
- Metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) responds well to immune checkpoint inhibition (CPI).
- The pathological impact of CPI on tumor response in dMMR mCRC is not well understood.
- Assessing pathological response is crucial for refining treatment strategies.
Purpose of the Study:
- To evaluate the pathological tumor response and clinical outcomes in dMMR mCRC patients treated with CPI before surgery.
- To determine if residual radiographic tumor after CPI requires resection.
Main Methods:
- Retrospective analysis of 121 dMMR mCRC patients treated with CPI.
- Focus on 14 patients who underwent surgical resection of primary or metastatic tumors.
- Analysis of pathological response in resected specimens and clinical follow-up.
Main Results:
- Pathologic complete response was achieved in 13 out of 14 surgically treated patients.
- Residual tumor on preoperative imaging was present in 12 of these patients.
- No disease relapse or progression observed during a median 9-month follow-up.
Conclusions:
- CPI induces significant pathological tumor response in dMMR mCRC.
- Residual radiographic tumor after CPI may not necessitate resection.
- Larger prospective studies are needed to confirm these findings and guide clinical practice.
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