(Colorectal Cancer) Efficacy of Imfinzi + Tremelimumab Based on Tumor Mutation Burden?
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At the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting held in Chicago from May 31 to June 4, 2019, results were presented from the CCTG CO.26 Phase II clinical trial evaluating the efficacy and safety of anti-PD-L1 antibody Imfinzi (durvalumab) plus anti-CTLA-4 antibody tremelimumab in patients with refractory metastatic colorectal cancer (rmCRC), with analysis of tumor mutation burden (TMB) within microsatellite-stable (MSS) tumors.
The CCTG CO.26 Phase II trial randomly assigned patients with refractory metastatic colorectal cancer (N=180) into two groups. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety.
- Combination Imfinzi + tremelimumab group (28-day cycle: Imfinzi 1500 mg + tremelimumab 75 mg on Day 1, for up to four cycles).
- Best supportive care (BSC) group.
With a median observation period of 15.2 months, the primary endpoint results were:
- OS: Imfinzi + tremelimumab group 6.6 months / BSC group 4.1 months.
Secondary endpoints:
- PFS: Imfinzi + tremelimumab group 1.8 months / BSC group 1.9 months.
- Disease control rate: Imfinzi + tremelimumab group 22.7% / BSC group 6.6%.
Blood samples were collected from 169 patients and used to analyze microsatellite instability via circulating free DNA in 168 patients. Of these, 2 had high microsatellite instability and 166 were microsatellite stable. Among MSS patients, the mean TMB was 20.4 ± 16.3 mts/Mb.
In patients with TMB ≥28 mts/Mb, OS was:
- Imfinzi + tremelimumab group 5.5 months / BSC group 3.0 months — a statistically significant improvement for the combination group.
In patients with TMB <28 mts/Mb, OS was:
- Imfinzi + tremelimumab group 6.9 months / BSC group 5.3 months — no significant difference between the groups.
Based on the CCTG CO.26 results, Eric Xueyu Chen concluded: In patients with refractory metastatic colorectal cancer that is MSS with high tumor mutation burden, the combination of anti-PD-L1 antibody Imfinzi and anti-CTLA-4 antibody tremelimumab significantly improved overall survival.
Source: CCTG CO.26: Updated analysis and impact of plasma-detected microsatellite stability (MSS) and tumor mutation burden (TMB) in a phase II trial of durvalumab (D) plus tremelimumab (T) and best supportive care (BSC) versus BSC alone in patients (pts) with refractory metastatic colorectal carcinoma (rmCRC). (2019 ASCO Annual Meeting, Abstract No: 3512)
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