Details

Autor(en) / Beteiligte

• André, T.
• Lonardi, S.
• Wong, K.Y.M.
• Lenz, H.-J.
• Gelsomino, F.
• Aglietta, M.
• Morse, M.A.
• Van Cutsem, E.
• McDermott, R.
• Hill, A.
• Sawyer, M.B.
• Hendlisz, A.
• Neyns, B.
• Abdullaev, S.
• Memaj, A.
• Lei, M.
• Dixon, M.
• Kopetz, S.
• Overman, M.J.

Titel

Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142

Ist Teil von

• Annals of oncology, 2022-10, Vol.33 (10), p.1052-1060

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients. Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1). A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation. The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals. •In previously treated MSI-H/dMMR mCRC, nivolumab plus ipilimumab showed durable benefit with 4 years of follow-up.•ORR was 65%. The 48-month rates of progression-free survival and overall survival were 53% and 71%, respectively.•Significant and clinically meaningful improvements in quality of life were largely maintained with continuous treatment.•No new safety signals were identified, with a low rate (13% of patients) of any-grade TRAEs leading to discontinuation.•These results show the long-term benefit of nivolumab plus low-dose ipilimumab in previously treated MSI-H/dMMR mCRC.