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ESMO 2018: Small Study of Preoperative Nivolumab Plus Ipilimumab in dMMR Colon Cancer

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Key Points

  • Results showed that 100% (7/7) of the patients with dMMR colon cancer had major pathologic responses (defined as < 5% of viable tumor cells remaining).
  • Four of these seven patients (57%) had complete responses.

Neoadjuvant treatment with a combination of the immune checkpoint inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy) achieved major pathological responses in mismatch repair­–deficient (dMMR) early-stage colon cancers, according to results reported by Chalabi et al at the European Society for Medical Oncology (ESMO) 2018 Congress (Abstract LBA37_PR) from the first exploratory phase II trial to investigate this approach.

Restoring patients' immune response against cancer cells with checkpoint inhibitors is an established treatment strategy for several tumor types. These agents are of particular interest in dMMR tumors, because they have a high mutational load and upregulation of immune checkpoints (according to findings from Sclafani et al in The Lancet Oncology).

Methods and Results

In the exploratory trial presented at ESMO, 14 patients with early-stage colon cancer were treated with nivolumab (2 doses of 3 mg/kg on days 1 and 15) and ipilimumab (1 dose of 1 mg/kg on day 1) before surgery.

Results showed that 100% (7/7) of the patients with dMMR colon cancer had major pathologic responses (defined as < 5% of viable tumor cells remaining). Four of these seven patients (57%) had complete responses. In contrast, no major pathologic responses were seen in mismatch repair–proficient tumors—however, there were significant increases in T-cell infiltration.

The immunotherapy regimen was well tolerated, and all of the patients underwent radical resection of their tumors without delays in surgery.

"This is the first study with immune checkpoint inhibitors in early-stage colon tumors. Our data suggest that neoadjuvant immunotherapy in dMMR colon cancer warrants further research and has the potential to change the standard of care," said lead author Myriam Chalabi, MD, of the Netherlands Cancer Institute, Amsterdam, in a statement. She commented, "The response we saw is much more dramatic than in metastatic disease, which we did not expect."

She continued, "For dMMR tumors, the results were amazing, with 100% of patients so far having either complete or near-complete responses within the short time frame of treatment, which is usually 4 weeks. I think the finding will have implications for clinical practice in the future. At this stage, it's too early to call it practice-changing, but it could be if similar results are seen in larger studies."

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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