ASCO Expert Perspective 

“This is the first phase III study demonstrating that combination immunotherapy with nivolumab plus ipilimumab is better than chemotherapy for patients with MSI-H/dMMR metastatic colorectal cancer. With fewer serious adverse events that are different than the standard chemotherapy-associated side effects, this treatment combination may offer a new first-line treatment option,” said Pamela Kunz, MD, ASCO Expert. 

Study at-a-Glance 

ALEXANDRIA, Va. — The dual immunotherapy combination of nivolumab and ipilimumab reduced the risk of disease progression or death by 79% compared to chemotherapy with or without targeted therapies as first-line treatment in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer. The research will be presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, taking place January 18-20 in San Francisco, California.  

About the Study 

Patients aged 18 or older with recurrent or metastatic colorectal cancers that were microsatellite high or had mismatch repair deficiency according to local testing were enrolled in the CheckMate 8HW trial. Mismatch repair deficiency (dMMR) is a genetic change that affects the ability of cells to repair damage to their DNA. Because of this instability, MSI-H/dMMR tumors often develop many mutations in their DNA. These mutations create unusual proteins on the tumor cells that make it easier for immune cells to find and attack the tumor.  

A total of 839 patients with previously untreated metastatic colorectal cancer were randomized 2:2:1 to receive one of three treatment regimens: nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. Treatments continued in all arms until disease progression or toxicity became unacceptable, or for a maximum of 2 years in the nivolumab ± ipilimumab arms. Dual primary endpoints were progression-free survival for nivolumab plus ipilimumab vs. chemotherapy with or without targeted therapies in the first-line treatment setting and nivolumab plus ipilimumab vs. nivolumab alone for all treatment settings.  

Key Findings 

• In the first-line setting, 303 patients were randomized to nivolumab plus ipilimumab (n = 202) or chemotherapy with or without targeted therapies (n = 101); of these patients, 171 patients in the nivolumab plus ipilimumab arm and 84 patients in the chemotherapy arm had centrally confirmed MSI-H/dMMR colorectal cancers. 
  • At 24.3 months of median follow-up, 72% of patients treated with nivolumab plus ipilimumab and 14% of patients treated with chemotherapy were alive without disease progression. These patients did not experience disease progression after two years from start of treatment.  
  • Nivolumab plus ipilimumab reduced the risk of disease progression or death by 79% compared to chemotherapy ± bevacizumab or cetuximab in these patients with centrally confirmed MSI-H/dMMR mCRC. 
  • There was a sustained difference in progression-free survival between the groups starting at approximately 3 months. 

Nivolumab plus ipilimumab had a different safety profile compared with chemotherapy, with fewer grade 3/4 treatment-related side effects. 

“These exciting results from the CheckMate 8HW study have potentially practice-changing implications for previously untreated patients with MSI-H/dMMR mCRC. Additional data may help define the further benefit of the combination of nivolumab and ipilimumab compared to nivolumab alone and help oncologists determine the best treatment options for their patients,” said lead study author Thierry Andre, MD, from the Sorbonne Université.  

Next Steps  

The CheckMate 8HW study is currently ongoing to assess the additional dual primary endpoint of PFS in patients receiving nivolumab plus ipilimumab compared to nivolumab alone across all lines of therapy, as well as secondary endpoints, including overall survival.   

“It remains crucial to identify predictive factors that can aid in the clinical decision-making process when choosing between immune checkpoint inhibitor monotherapy or combination. While single agent immunotherapy has previously demonstrated improved outcomes over conventional chemotherapy in patients with MSI-H/dMMR metastatic colorectal cancer, an unmet need remains in this setting. Identifying patients who would benefit from dual immunotherapy combination aligns with optimizing treatment choices to help deliver the best possible outcome for these patients,” said Dr. Andre.

The CheckMate 8HW study was sponsored by Bristol Myers Squibb. 

View the full embargoed abstract (Please note: You must enter your name and email address to view the abstract.)

View author disclosures (Link will be added shortly)

View the News Planning Team disclosures: https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/about-asco/pdf/2024-asco-gi-npt-disclosures.pdf

ATTRIBUTION TO THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY GASTROINTESTINAL CANCERS SYMPOSIUM IS REQUESTED IN ALL COVERAGE. 

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