Julien Taieb, MD, PhD
The invited discussant for the CheckMate-142 findings was Julien Taieb, MD, PhD, Professor of Medicine at Paris Descartes University in France. Dr. Taieb called the findings “impressive” but said longer follow-up is needed, especially since median outcomes have not yet been reached. After a treatment duration of almost 1 year, the exposure to nivolumab (Opdivo) plus low-dose ipilimumab (Yervoy) was “good,” and the ratio between the two drugs was appropriate, he noted.
Among the three cohorts in CheckMate-142 (first-line nivolumab/ipilimumab, second-line nivolumab/ipilimumab, and single-agent nivolumab), the current analysis reveals the largest response rate, 60%, compared with 51% and 31%, respectively, for the 2 other cohorts, he pointed out. “The 60% response rate is quite impressive,” he commented.
The first-line schedule produced a 12-month progression-free survival rate of 77% and an overall survival rate of 85%, compared to 50% and 73%, respectively, for single-agent nivolumab in previously treated patients. “The survival curves are quite flat at the end, which is a good signal for our patients,” he said.
“Are these results incredible?” Dr. Taieb asked. They do not appear different from what can be achieved with intensive chemotherapy, he said, according to recently published data from his group in first-line metastatic rectal cancer (all comers).1 With induction FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin), the 4-month disease control rate was 94%, the response rate was 86%, and more than a 70% decrease in primary tumor volume was achieved by 63% of patients, his group reported.2
“You don’t do much better than with this intensive regimen,” he noted, “but you’re using chemotherapy, not immunotherapy, and the tolerability profile is different.”
The survival outcomes seen with nivolumab plus low-dose ipilimumab are also not much better than are already being achieved, according to unpublished data from the ACCENT database, which documents 1-year survival for patients with metastatic microsatellite instability–high/mismatch repair deficiency to be about 80%, he added, as also reported by Sinicrope et al.
“But you see that with immunotherapy, the curve flattens, and there’s not much difference between 9-month and 12-month survival,” he pointed out. “I think there is something here, but absolute values can be confusing, and we need to follow this out further.” ■
DISCLOSURE: Dr. Taieb has received honoraria and served in a consulting or advisory role for Roche Genentech, Lilly, Servier, Sanofi, Celgene, Shire, Amgen, Sirtex, Merck Serono, and MSD; and has received travel expenses from Merck Serono and Celgene.
1. Bachet JB, et al: FOLFIRINOX as induction treatment in rectal cancer patients with synchronous metastases. Eur J Cancer 104:108-116, 2018.
2. Bachet JB, et al: FOLFIRINOX as induction treatment in rectal cancer patients with synchronous metastases. Eur J Cancer 104:108-116, 2018.
3. Sinicrope FA, et al: Association of DNA mismatch repair and mutations in BRAF and KRAS with survival after recurrence in stage III colon cancer. JAMA Oncol 3:472-480, 2017.
In previously untreated patients with metastatic colorectal cancer and tumors demonstrating microsatellite instability–high (MSI-high) or mismatch repair deficiency (dMMR), immunotherapy with nivolumab (Opdivo) and low-dose ipilimumab (Yervoy) produced a durable clinical benefit in the...