Cabozantinib is FDA approved for the treatment of several types of cancer including advanced renal cell and hepatocellular carcinoma and thyroid cancer. A single-arm phase 2 study showed that cabozantinib was safe and demonstrated encouraging efficacy in heavily pre-treated metastatic CRC patients [8, 9]. Best response was 1 partial response and 31 with stable disease with a disease control rate at 6 weeks of 72.7%. Of the patients who achieved ≥12 weeks PFS, 12 had left-sided primary tumours, 5 had a RAS mutation, 1 had a PIK3CA mutation, and all patients were BRAF wild-type and MSI stable [8]. Durvalumab is FDA approved for other types of cancer including non-small cell lung cancer and small cell lung cancer. A phase 2 trial (CAMILLA trial) demonstrated that the combination of cabozantinib and durvalumab appeared safe and demonstrated efficacy among a small cohort (n=29) of patients with advanced mismatch repair- proficient/microsatellite-stable CRC. The 29 patients evaluable for the efficacy analysis had an overall response rate (ORR )of 27.6%, confirmed partial response rate of 20.7% and disease control rate of 86.2% [10]. Durvalumab (Imfinzi) is a humanized monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80 to release the inhibition of immune responses, without inducing antibody-dependent cell-mediated cytotoxicity [11]. This combination may show promise for the patient who has a metastatic sigmoid rectal MSS tumour.
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