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Immunotherapy improved progression-free survival when added to first-line chemotherapy, particularly in patients with mismatch repair deficient tumors
The combination of chemotherapy and the immune checkpoint inhibitor avolumab showed improved progression-free survival in patients with advanced or recurrent untreated endometrial cancer, as shown by the italian multicentre phase 2 trial MITO END-3 recently published on The Lancet Oncology.
For patients with recurrent or metastatic endometrial cancer, the first-line treatment consists of chemotherapy with carboplatin and paclitaxel or hormonal therapy depending on histological and clinical features; however, introduction of immunotherapy might change the treatment framework since endometrial cancer is an immunogenic tumor. Thus, the MITO END3 phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy, aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment for patients with advanced or recurrent endometrial cancer, with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy. 125 patients were randomized to either receive carboplatin and paclitaxel intravenously every 3 weeks for six to eight cycles or avelumab added to carboplatin and paclitaxel every 3 weeks and then every 2 weeks as a single maintenance treatment after the end of chemotherapy, until disease progression or unacceptable toxicity. After a median follow up of 23.3 months, the median progression-free survival was 9.9 months in the standard group and 9.6 months in the experimental group. Longer progression-free survival was driven by the mismatch repair deficient population, in whom the benefit was evident and overall survival curves showed a clinically significant benefit, whereas other patients did not benefit from the addition of immunotherapy. «Advanced endometrial cancer is challenging to treat and patients usually receive chemotherapy, which results in low response rates», authors write. «The use of immunotherapy in a first-line setting combined with chemotherapy could be a valuable option to improve the outcome of patients with advanced or recurrent endometrial cancer: our results support further research to verify whether avelumab might be an effective adjunct to chemotherapy as first-line treatment for patients with advanced or recurrent endometrial cancer labelled as mismatch repair deficient at immunohistochemistry», authors conclude.