CHICAGO — Nivolumab with or without ipilimumab was well tolerated in most patients with high microsatellite instability metastatic colorectal cancer (mCRC) and demonstrated encouraging clinical activity and survival, a study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting showed.1
“Although approximately 15% of elderly CRCs display a high degree of microsatellite instability, indicating a deficient DNA mismatch repair system, high microsatellite instability is found in approximately 4% of mCRC,” said Michael Overman, MD, associate professor in the department of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, in Houston, TX. “High microsatellite instability CRC is known to have an exceptionally high mutation burden.”
Previous research has supported the use of nivolumab in high microsatellite instability mCRC. Because the combination of nivolumab and ipilimumab has favorable safety and efficacy in other cancers, researchers aimed to evaluate nivolumab with or without ipilimumab in patients with high microsatellite instability mCRC and in patients without high microsatellite instability mCRC in a phase 2 study.
For the CheckMate 142 trial, researchers enrolled 100 patients with high microsatellite instability and 20 patients with microsatellite stability. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received at least 1 prior therapy.
Patients with high microsatellite instability received nivolumab 3 mg/kg every 2 weeks or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks until disease progression. Patients with microsatellite stability received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, both followed by nivolumab 3 mg/kg every 2 weeks.
Among the patients with high microsatellite instability, the objective response rate was 25.5% for nivolumab monotherapy and 33.3% for the combination, all of which were confirmed partial responses. Median duration of response has not yet been reached in either group.
“Nivolumab monotherapy demonstrated encouraging activity in patients with high microsatellite instability status and the combination also demonstrated promising preliminary activity,” Dr Overman noted. “Response to nivolumab monotherapy and the nivolumab plus ipilimumab combination were durable in patients with high microsatellite instability.”
Researchers found that the 12-month progression-free survival rate was 45.9% (95% CI, 29.8-60.7) with nivolumab alone and has not yet been determined with nivolumab plus ipilimumab. The 12-month overall survival rate was 65.6% (95% CI, 48.0-78.6) with nivolumab and has not yet been reached with nivolumab plus ipilimumab
In patients with microsatellite stability, there was only 1 objective response; median progression-free survival ranged from 1.31 to 2.28 months across both cohorts; and median overall survival ranged from 3.73 to 11.53 months across the 2 combination arms.
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In regard to safety, treatment-related adverse events occurred in 58.6% of the nivolumab monotherapy-treated patients with high microsatellite instability and in 83.3% of those treated with the combination. The most common adverse events included diarrhea and fatigue in the monotherapy group and pyrexia and diarrhea in the combination arm. Of note, 1 patient receiving single-agent nivolumab died suddenly due to nivolumab therapy.
“Nivolumab and the combination of nivolumab and ipilimumab demonstrated tolerable safety profiles in relation to clinical benefit and were consistent with observations in other solid tumors,” Dr Overman added.
“Results are encouraging and support continued evaluation of nivolumab monotherapy and nivolumab plus ipilimumab in patients with high microsatellite instability mCRC and potentially other tumors with mismatch repair defects,” he concluded.
- Overman MJ, Kopetz S, McDermott RS, et al. Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results. J Clin Oncol. 2016; 34 (suppl; abstr 3501).