- Checkmate 8HW is the first phase III study to assess first-line nivolumab plus ipilimumab in patients with unresectable microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).
- Initial results from this study, presented today at the 2024 ASCO Gastrointestinal Cancers Symposium*, show that the dual immunotherapy regimen reduced the risk of disease progression by 79% compared with standard chemotherapy.
- Nivolumab plus ipilimumab is currently approved as second-line therapy for previously treated MSI-H/dMMR metastatic colorectal cancer. Promising first results from the Checkmate 8HW study point to this combination as a potential treatment option for first-line mCRC.
First results of the Checkmate 8HW phase III trial, co-authored by Elena Élez, a Medical Oncologist at the Vall d’Hebron University Hospital and Group Leader of VHIO’s Colorectal Cancer Group, show that first-line treatment with nivolumab plus ipilimumab significantly improves outcomes compared with chemotherapy in patients with unresectable microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).
Colorectal cancer is the third most common cancer globally, accounting for approximately 10% of all cancer cases and is the second leading cause of cancer-related deaths worldwide. Approximately 50% of patients with colorectal cancer will eventually develop metastatic disease.
Between 5 and 7% of newly diagnosed mCRC cases belong to the MSI-H/dMMR molecular subtype of disease. If metastatic colorectal cancer cannot be treated with surgery, the current first-line treatment is immunotherapy with pembrolizumab or standard chemotherapy.
“These patients typically respond poorly to chemotherapy, and while checkpoint inhibition with pembrolizumab was recently approved as first-line therapy in patients with previously untreated MSI-H/dMMR mCRC, there remains an unmet clinical need for some of these patients,” says Elena Élez.
Aimed at identifying alternative treatment options for this patient population, the investigators evaluated if the combination of dual immunotherapy with nivolumab plus ipilimumab could delay disease progression and reduce the risk of death for patients with MSI-H/dMMR mCRC. Nivolumab is a PD-1 inhibitor and ipilimumab is a CTLA-4 inhibitor and this combination is currently approved as second-line therapy for previously treated MSI-H/dMMR mCRC.
Led by Thierry André, Professor of Medical Oncology at the Sorbonne Université, and Head of the Medical Oncology Department at the Hôpital Saint Antoine, Assistance Publique Hôpitaux in Paris, Checkmate 8HW included 303 patients with mCRC who were randomly assigned to receive either a combination of nivolumab and ipilimumab (202 people) or chemotherapy (101 people). There were 255 participants, 171 in the immunotherapy group and 84 in the chemotherapy group, who had confirmed MSI-H/dMMR colorectal cancer.
Initial results from this study, presented today as late-breaking data at the 2024 ASCO Gastrointestinal Cancers Symposium (ASCO GI)*, 18-20 January in San Francisco, show a 79% reduction in the risk of disease progression with the immunotherapy combination compared with chemotherapy. For the 255 participants with MSI-H/dMMR colorectal cancer, the primary endpoint was progression-free survival (PFS).
The participants were followed for a median of 24.3 months, and during that period the median PFS was not reached for the immunotherapy group, meaning that more than half of these patients had not experienced disease progression. The median PFS for the chemotherapy group was 5.8 months. In addition, patients treated with dual immunotherapy c had less treatment-related side effects compared with the chemotherapy group.
The promising first results from this study, the first phase III clinical trial to evaluate first-line nivolumab plus ipilimumab in this patient population, show that this treatment combination delays cancer growth in patients with MSI-H/dMMR metastatic colorectal cancer in comparison to a current standard of care with chemotherapy.
“The next step will be to evaluate the efficacy of this combination versus a PD-1 inhibitor alone in the clinical trial given that this is the current standard of care for the treatment of previously untreated patients with MSI-H/dMMR mCRC,” concludes Elena Élez.
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*2024 ASCO Gastrointestinal Cancers Symposium (ASCO GI), 18-20 January, San Francisco. Respective session details and access to the corresponding late-breaking abstract: https://meetings.asco.org/2024-asco-gastrointestinal-cancers-symposium/15577?presentation=230735#230735.
