Immunotherapy Combination Receives FDA Approval for Metastatic Colon and Rectal Cancer

On 10 July 2018, the US Food and Drug Administration FDA, after fluoropyrimidine, oxaliplatin and irinotecan treatment had failed and disease progressed, in patients with high microsatellite instability(MSI-H) or DNA mismatch repair deficiency (dMMR), older than 12 with metastatic colon and rectal cancer, granted accelerated approval to nivolumab (Opdivo) combined with low-dose ipilimumab (Yervoy).

Nivolumab alone had received accelerated approval for this on 31 July 2017; the new approval updated its label.

Approval is based on a multicenter, nonrandomized, open-label trial involving metastatic colon and rectal cancer patients with progression after standard first-line treatment and positive dMMR or MSI-H, totaling 82 patients, called CHECKMATE 142.

• What to Know About Colon and Rectal Cancer

All patients first received every 3 weeks ipilimumab 1 mg/kg (low dose) plus nivolumab 3 mg/kg for 4 doses, then every 2 weeks nivolumab 3 mg/kg until unacceptable adverse effects or radiological progression.

Study Results:

• Objective response was %46. Complete responses occurred in 3 patients and partial responses in 35.
• In %89 of patients, responses lasted at least 6 months
• The combination had higher objective response than nivolumab alone (another study with similar patients, numbering 58, found %28 with nivolumab alone).

The common effects (≥% 20) with ipilimumab and nivolumab were fatigue, diarrhea, fever, musculoskeletal pain, abdominal pain, itching, nausea, rash, dyspnea, decreased appetite and vomiting.

• What Are Immunotherapy Adverse Effects, and How Are They Treated?

For this use, recommended dosesare: every 3 weeks, ipilimumab 1 mg/kg (low dose) plus nivolumab 3 mg/kg for 4 doses; then every 2 weeks nivolumab 240 mg.