Opdivo Regimens Improve Long-Term Colorectal Cancer Outcomes

Patients previously treated for DNA mismatch repair (MMR)-deficient/microsatellite instability-high (MSI-H) metastatic colorectal cancer may have a new effective treatment option.

Data from the CheckMate-142 trial, presented at the 2018 Gastrointestinal Cancers Symposium, showed that Opdivo (nivolumab) alone and in combination with Yervoy (ipilimumab) was proven to be safe and effective in this patient population.

Results from this trial are important, as CheckMate-142 is the largest single-study report of an immunotherapy regimen in patients with MMR-deficient/MSI-H metastatic colorectal cancer.

Opdivo has been found to provide durable responses and disease control in pretreated patients with MMR-deficient/MSI-H colorectal cancer. It was also approved by the Food and Drug Administration (FDA) for these patients who progressed after standard chemotherapy.

Therefore, researchers at The University of Texas MD Anderson Cancer Center in Houston and Hôpital Saint Antoine in Paris, France, provided updates on the agent as a monotherapy and combination regimen.

Long-Term Responses

In this update, Michael J. Overman, M.D., assistant professor in the Department of Gastrointestinal Medical Oncology at MD Anderson Cancer Center, offered data on long-term survival and outcomes in patients treated with Opdivo alone.

Of the 74 patients evaluated in the study, 53 previously received chemotherapy with a fluoropyrimidine, oxaliplatin and irinotecan and 21 were given two or more lines of standard chemotherapy.

All of the patients received 3 mg/kg of Opdivo every two weeks. The researchers were primarily looking at overall response rate, and they also evaluated disease control rate, duration of response, progression-free survival (PFS), overall survival (OS) and safety/tolerability.

All patients continued to provide clinically meaningful and durable responses. Overall response rate at 21 months was 34 percent, including a complete response in seven patients and a partial response in 18. From the previous analysis, five additional patients achieved a complete response between median follow-up at 13 months and 21 months.

“Deepening of response was shown with further follow-up…primarily related to partial responses that converted to complete responses with additional time,” said Overman.

Twenty-three percent of patients had stable disease while 22 patients had progressive disease, resulting in a disease control rate of 62 percent. Median OS was not reached as of the 21-month follow-up, but at 18 months it was at 67 percent.

Median PFS was 6.6 months, which, “does not well represent the benefit from this therapy,” Overman said. ““What’s better representation is that at 12 months, we see a PFS rate of 44 percent, which at 18 months is exactly the same, at 44 percent. These are similar across [the different chemotherapy regimen groups].”

No new safety/tolerability profiles were reported with this long-term follow-up.

These enhanced responses support ongoing evaluation of Opdivo-based therapy in the first-line setting in patients with MMR-deficient/MSI-H metastatic colorectal cancer, Overman said.

Combination Efficacy and Safety

In this update, Thierry André, M.D., medical director of Gastroenterology Oncology Unit at Hôpital Saint Antoine, provided first time efficacy and safety from 119 patients treated with Opdivo in combination with Yervoy.

In the trial, patients received 3 mg/kg of Opdivo plus 1 mg/kg of Yervoy every three weeks for four doses, followed by 3 mg/kg of Opdivo every two weeks.

The researchers evaluated overall response rate, as well as duration of response, PFS, OS and safety/tolerability over a follow-up of approximately 13.4 months.

The combination use of Opdivo and Yervoy provided durable clinical benefit with a high objective response rate of 55 percent, including 31 percent of patients with stable disease, and a disease control rate of 80 percent.

Patients experienced responses with the combination regimen at 2.8 months, and responses appeared durable. Median duration of response was not reached among treatment responders. However, 94 percent of responses were ongoing at data cutoff.

“We have only four patients who did not have ongoing response at data cutoff; one for partial disease, two deaths, and one for surgery of metastases and this patient was censored at the time of surgery,” said André.

Three-fourths of the patient population experience a reduced tumor burden from baseline. In addition, long-term survival appeared clinically significant with a nine-month PFS of 76 percent and OS of 87 percent.

No new safety signals or treatment-related deaths were observed.

“Opdivo plus Yervoy represents a promising new treatment option for patients with previously treated MMR-deficient/MSI-H metastatic colorectal cancer,” André said.