Colorectal tumors are one of the most common malignancies of the digestive system. In our country, the annual incidence rate of colorectal cancer is about 4.2 per thousand, which has reached or even exceeded the average level of western developed countries, and the age of patients is showing a younger trend. Recently, the results of a study of Avelumab Avelumab combined with Cetuximab Cetuximab for the treatment of RAS gene wild-type (wt) metastatic colorectal cancer (mCRC) were announced at the 2020 ESMO annual meeting, showing that this strategy has a certain feasibility.
Avelumab Avelumab International Research data
CAVE Colon is a single-arm, multicenter phase II study designed to evaluate the efficacy and safety of avelumab in combination with cetuximab in previously treated RAS wt% mCRC patients. Enrollment criteria included: pathologically confirmed KRAS (exons 2, 3, and 4) and NRAS (exons 2, 3, and 4) WT mCRC, receiving first-line CT combined with anti-EGFR therapy with a major response (complete or partial), progressing to second-line therapy, and having not previously received immunotherapy. The primary endpoint was overall survival; secondary endpoints were overall response rate, progression-free survival, and safety profiles according to RECIST 1.1. Previous studies have shown that the median overall survival (OS) for this group of patients with standard third-line therapy is 8.0 months. The new combination therapy regimen can achieve a median OS of 11 months, equivalent to increasing the 6-month OS from 40% to 57%. This study will validate the efficacy and safety of this experimental combination therapy. From August 10, 2018 to February 21, 2020, 77 patients were enrolled and started treatment, receiving Avelumab 10 mg/kg q14 IV infusion over 1 hour + Cetuximab 400 mg/m2 IV infusion over 2 hours, followed by Cetuximab 250 mg/m2 q7 IV infusion over 1 hour until disease progression or unacceptable toxicity. Using the Kaplan-Meier method to predict survival curves, the median survival in the intention-to-treat (ITT) population was 13.1 months (90% CI, 8.1–18.0 months; 32 events); the median progression-free survival was 3.6 months (95% CI, 3.2–4.1 months; 62 events). Of these, 1 patient (1%) achieved complete remission (CR), 5 patients (6%) achieved partial remission (PR), and 44 patients achieved stable disease (SD) (57%); 27 patients (35%) experienced disease progression (PD), resulting in a disease control rate (DCR) of 65%. Patients with progression-free survival of 6 months or more accounted for 12/65 (18.5%). Grade 3 adverse events were reported in 16 of the 77 patients (22%), most commonly rash (10/77, 13%) and diarrhea (3/77, 4%). Subgroup analysis showed that patients with RAS/BRAF WT mCRC identified by ctDNA testing had a median overall survival (OS) of 16.1 months, a median progression-free survival (PFS) of 4.3 months, and a DCR of 73%.
Avelumab Avelumab Drug introduction
Product name: Bavencio
Drug name: Avelumab
Chinese name: Avirumab
Drug specification: 200mg/10ml
Manufacturers: Pfizer, USA and Merck, Germany
Indications: It has been approved for the treatment of Merkel cell carcinoma, bladder cancer and kidney cancer.
Avelumab is a programmed death-ligand-1 (PD-L1) blocking antibody. PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells, potentially contributing to the suppression of anti-tumor immune responses in the tumor microenvironment. PD-L1 binds to PD-1 and B7.1 receptors on T cells and antigen-presenting cells, inhibiting cytotoxic T cell activity, T cell proliferation, and cytokine production. Avelumab binds to PD-L1, thereby blocking the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effect of PD-L1 on the immune response, leading to the restoration of the immune response, including anti-tumor immune responses.
Reminder: Preliminary results show that Avelumab combined with cetuximab as a re-challenge strategy is effective and well tolerated in patients with chemotherapy-refractory RAS WT mCRC.
