Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab. MATERIALS AND METHODS: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety. RESULTS: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death. CONCLUSION: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.

Primary synovial sarcoma of the kidney. A case report with pathologic appraisal investigation and literature review.

Synovial sarcoma (SS) is a soft tissue neoplasm with clearly defined histologic, immunohistochemical and molecular features that usually arises in the extremities of young adults. The occurrence of these tumors in the kidney is extremely rare and have been prevalently described in case reports. The objectives of this work were to evaluate the frequency of primary renal synovial sarcomas and the pathologic progression in recognition of this possibly under-diagnosed entity. A comprehensive review of the literature has also been performed with a focus on survival. We report the clinico-pathological features of an intrarenal SS occurring in a 67-year-old man. The tumour, measuring 4 cm in its greatest diameter, completely replaced the cortex and the medulla of the inferior region of the left kidney compressing the iliopsoas muscle. Radiological imaging was consistent with a renal cell carcinoma. Histologically, the tumour was composed of atypical monotonous vimentin+, CD99+, bcl-2+ spindle cells exhibiting a haphazard fascicular growth pattern and a high mitotic rate (3 to 5 mitoses per HPF). The diagnosis was supported by reverse transcription-polymerase chain reaction which demonstrated SYT-SSX2 gene fusion. The patient was alive with local recurrence of disease 24 months after surgery. Synovial sarcomas occurring in the kidney, in analogy to other sites, tend to have an aggressive biologic behaviour. Despite being extremely uncommon, with only 44 cases reported to date, they should be included in the differential diagnosis of benign and malignant spindle cell tumours of the kidney. This study also emphasizes the importance of a correct pathologic diagnosis for prognostic and therapeutic implications.