Combination Immunotherapy Prolongs Overall Survival of mCRC


Immunotherapy has been approved for the treatment of metastatic colorectal cancer (mCRC) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). However, the immunotherapy has shown the limited anti-tumor activity in patients with microsatellite-stable (MSS) or mismatch repair proficient (pMMR). A randomized phase II trial (CCTG CO.26) investigating combination immunotherapy for mCRC treatment was presented in 2019 Gastrointestinal Cancers Symposium. Patients with mCRC refractory of all available therapy were enrolled and treated with durvalumab plus tremelimumab plus best supportive care or best supportive care alone. The percentage of MSS/pMMR in the experimental and control cohort were 98% and 80%, respectively. The overall survival of immunotherapy treated group and control group was 6.6 months and 4.1 months. Furthermore, in 2019 ASCO Annual Meeting, the updated analysis of this trial showed that blood tumor mutation burden (bTMB) can be used to select patients who benefit from immunotherapy treatment. In patients with bTMB >28, the hazard ratio of overall survival was 0.34, p=0.004; In patients with bTMB <28, the hazard ratio of overall survival was 0.76, p=0.21. These results revealed the potential of the anti-tumor activity of combination immunotherapy in the heavily treated mCRC and the role of bTMB for patient selection.

Chen EX, et al. ASCO annual meeting 2019