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NEJM Research

Opdivo (nivolumab) + Yervoy (ipilimumab) in First-Line MSI-H Metastatic Colon Cancer. What Did the CheckMate-8HW Trial Show

The results of CheckMate-8HW in patients with MSI-H unresectable or metastatic colon cancer were recently published in one of the world's leading oncology journals. First-line Opdivo (nivolumab) + Yervoy (ipilimumab) was compared with chemotherapy. The combination showed a convincing benefit in progression-free survival and better tolerability in terms of severe adverse events.

In brief: what happened

The first-line analysis included 303 patients who had not previously received systemic therapy for metastatic disease.

  • In 255 patients, MSI-H status was confirmed by central testing.
  • The 24-month progression-free survival was 72% with dual immunotherapy versus 14% with chemotherapy.
  • Grade 3–4 treatment-related adverse events occurred in 23% of patients on immunotherapy and in 48% on chemotherapy.

Key numbers from the trial

At a median follow-up of 31.5 months, progression-free survival was statistically significantly better with the combination of nivolumab and ipilimumab than with chemotherapy. For MSI-H colorectal cancer, this is one of the strongest randomized confirmations of the advantage of an immune-based approach in the first line.

Why this matters in practice

In MSI-H metastatic colon cancer, the question of choosing the first line has long moved beyond standard cytotoxic chemotherapy. CheckMate-8HW further reinforces the need for molecular profiling already at the start.

Limitations / what does not change yet

These data apply only to MSI-H tumors. They do not extend to colon tumors without microsatellite instability. Correct molecular diagnostics are of key importance.

When a second opinion is especially useful

  • the molecular MSI status has not yet been determined;
  • standard chemotherapy is being proposed without discussing immunotherapy;
  • doctors' opinions differ regarding the first line;
  • it is important to understand to what extent the aggressiveness of the disease allows waiting for the effect of immunotherapy.

What to prepare for the consultation

  • histopathology report;
  • results of testing for microsatellite instability;
  • CT of the chest, abdomen and pelvis;
  • discharge summary with the clinical diagnosis and stage;
  • list of symptoms and comorbidities;
  • list of all medications you are taking.
Source: The New England Journal of Medicine: Nivolumab plus Ipilimumab in MSI-H Metastatic Colorectal Cancer

Frequently Asked Questions

Is this regimen suitable for all patients with metastatic colorectal cancer?

No. Only for patients with an MSI-H or dMMR tumor.

Is it mandatory to know the MSI/MMR status before choosing the first line?

Yes. After CheckMate-8HW this is a key parameter for discussing treatment.

Was the toxicity of dual immunotherapy worse than that of chemotherapy?

No. The rate of severe treatment-related adverse events was lower than with chemotherapy.

More answers on the FAQ page.

Discuss your situation with an oncologist

News provides general information. For an accurate assessment of your situation, an individual consultation with a review of your medical records and examination is needed. Answers to common questions are on the FAQ page.

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