Summary
First-line nivolumab plus low-dose ipilimumab over a 2-year period was associated with durable clinical benefit and deepening responses and featured a good tolerability profile in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), according to long-term follow-up data from the phase II CheckMate-142 trial, which were presented at the ASCO 2020 Annual Meeting (Abstract 4040).
This analysis of the CheckMate-142 trial included a total of 45 patients with MSI-H or dMMR mCRC who had data over a median follow-up period of 29 months (range, 24.2–33.7) available for analysis. All patients who entered the trial had no previous treatment for metastatic disease. During the study, participants received nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks until either progression of disease or discontinuation from the study. The investigator-assessed objective response rate (ORR) comprised the primary endpoint.
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Original Article
Nivolumab + Ipilimumab Produces Durable Responses in Metastatic Colorectal Cancer
Oncology Times
By Brandon May
First-line nivolumab plus low-dose ipilimumab over a 2-year period was associated with durable clinical benefit and deepening responses and featured a good tolerability profile in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), according to long-term follow-up data from the phase II CheckMate-142 trial, which were presented at the ASCO 2020 Annual Meeting (Abstract 4040).
This analysis of the CheckMate-142 trial included a total of 45 patients with MSI-H or dMMR mCRC who had data over a median follow-up period of 29 months (range, 24.2–33.7) available for analysis. All patients who entered the trial had no previous treatment for metastatic disease. During the study, participants received nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks until either progression of disease or discontinuation from the study. The investigator-assessed objective response rate (ORR) comprised the primary endpoint.
During the extended follow-up period, the ORR increased from 60 percent (95% CI, 44.3-74.3) to 69 percent (95% CI, 53-82), which represented 31 patients who experienced an investigator-assessed ORR. Overall, the rate of concordance of the investigator-assessed ORR and blinded independent central review was 89 percent.
The complete response rate (CR) to the combination regimen increased from 7 percent (n=3) to 13 percent (n=6), whereas the partial response rate increased to 56 percent (n=25). Additionally, the rates of stable disease and progressive disease were 16 percent (n=7) and 13 percent (n=6), respectively. Approximately 2 percent (n=1) of patients had a response that was not determined.
Over the median 29-month follow-up period, the median duration of response was not reached (range, 1.4+ to 29.0+), which suggests that the responses were very durable. The median time to response was 2.7 months (range, 1.2-27.7). Additionally, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 24-month PFS was 74 percent (95% CI, 57.2-84.5), whereas the 24-month OS rate was 79 percent (95% CI, 64-89).
A total of 19 patients discontinued treatment on the study without initiating any subsequent therapy. During the session, Heinz-Josef Lenz, MD, co-leader of the Gastrointestinal Cancers Program at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, presented an analysis of tumor response in these patients who discontinued therapy.
Approximately 22 percent (n=10) of patients experienced grade 3-4 treatment-related adverse events (TRAEs) during the 2-year treatment period. A total of 3 (7%) patients experienced grade 3-4 TRAEs that led to discontinuation of the study treatment.
Lenz, who presented these results at ASCO, told Oncology Times that the current treatment strategies for MSI-H of dMMR mCRC are lacking robust efficacy and safety profiles similar to that observed with the nivolumab plus low-dose ipilimumab used in the CheckMate-142 trial.
“Chemotherapy can be effective but significantly more toxic and less-effective,” he added. Considering patients with MSI-H or dMMR mCRC typically have a shorter survival compared with patients with non-MSI-H tumors when treated with first-line chemotherapy, these findings are particularly promising for clinical practice.
When asked how these long-term findings might impact clinical care of patients with MSI-H or dMMR mCRC, Lenz responded, “I think as this combination is included in the National Comprehensive Cancer Network guidelines, including for patients in first line who are not candidates for chemotherapy, it can be considered as a new option for first-line therapy.”
He noted that there is currently an ongoing trial comparing this treatment approach against chemotherapy, as well as chemotherapy with IO, to better understand the efficacy profiles of these therapeutic options.
Brandon is a contributing writer.