On July 11th, 2018, the Federal Drug Administration (FDA) approved the use of Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for patients over 12 years old with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) who have progressed on a previous treatment of fluoropyrimidine, oxaliplatin, and irinotecan.
This announcement is an exciting next step in colorectal cancer (CRC) treatment as it shows the impact of research and clinical trials.
The accelerated approval was granted based on positive results from the Checkmate-142 study as it relates to overall response rate and the duration of response. For the study, the overall response rate (ORR) is defined as tumor size reduction resulting directly from therapy, and the duration of response (DOR), which is defined as a long-lasting response to therapy.
I’ve heard of these drugs before…
Opdivo (nivolumab) and Yervoy (ipilimumab) have both previously been approved by the FDA.
This latest announcement affects CRC patients because it now allows these drugs to be used in combination for those with mCRC.
Yervoy is an immunotherapy-based treatment previously approved for metastatic melanoma and renal cell carcinoma. Opdivo (nivolumab) is a PD-1 inhibitor that was approved in August 2017 based on results from the Checkmate-142 study for dMMR/MSI-H mCRC for those whose cancer either progressed or did not respond after being treated with a fluoropyrimidine, oxaliplatin, and irinotecan.
What did Checkmate-142 investigate and what did they find?
The ongoing phase II Checkmate-142 study investigated nivolumab alone and in combination with ipilimumab, cobimetinib, anti-LAG-3 antibody, and daratumumab.
In the ipilimumab + nivolumab therapy arm, a total of 119 patients were treated with this combination. Approximately 12% were stage II, 44% were stage III, and 45% were stage IV. Tumor mutations included KRAS- positive (37%), BRAF/KRAS wild-type (26%), BRAF-positive (24%) and unknown (13%).
The overall response rate was 49%, and among the 58 patients that responded, five patients had a complete response, or no evidence of disease, and 53 had a partial response, meaning the cancer responded to treatment but did not fully go away.
Additionally, 82 patients in this group had previously received fluoropyrimidine, oxaliplatin, and irinotecan. The ORR of those that had received previous treatment was 46%. Of the 38 individuals that had a positive response, three achieved complete response, and an additional 35 achieved partial response.
The data from this study was published in the Journal of Clinical Oncology and presented at the 2018 Gastrointestinal Cancers Symposium in January. For more in depth information on methods and results from this study, you can read the full report here.
What does this mean for patients?
Research shows that patients with MSI-H/dMMR colorectal cancer respond much better to immunotherapy than those with MSS tumor types. The approval of this combination therapy provides another option for patients who present with MSI-H tumors.
While it may seem that research doesn’t always move as fast as we’d hope, it was less than a year ago that Opdivo was approved for MSI-H/dMMR CRC patients, and in that time, another combination has shown promise and been approved.
For patients, caregivers, and CRC champions, the approval of new drugs means new options and new hope.
Although this therapy isn’t advised for patients with MSS tumors, there are numerous studies looking at ways to harness the immune system in the fight against colorectal cancer.