Purpose: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor prognosis. Patients with MPM who do not respond to standard firstline chemotherapy have limited treatment options. We evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for the treatment of advanced or metastatic MPM. Patients and Methods: Japanese patients with unresectable, advanced, or metastatic MPM resistant or intolerant to 2 regimens of chemotherapy and 1 measurable lesion (s) were enrolled. Patients received nivolumab 240 mg intravenously every 2 weeks until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate by central assessment according to the Modified Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) and treatment-related AEs (TRAEs) were evaluated. Results: Thirty-four patients were enrolled between July 2016 and October 2016. Median follow-up was 16.8 (range: 1.8-20.2) months. Ten (29%, 95% confidence interval, 16.8-46.2) patients showed a centrally assessed objective response. The objective response rates were 26% (7/27), 67% (2/3), and 25% (1/4) patients for epithelioid, sarcomatoid, and biphasic histologic subtypes, respectively. Median duration of response was 11.1 months with a 68% disease control rate. Median overall survival and progression-free survival were 17.3 and 6.1 months, respectively. The objective response rate was 40% with programmed death-ligand 1 expression 1% and 8% with <1%. Thirty-two patients (94%) experienced AEs and 26 (76%) experienced TRAEs. Conclusions: Nivolumab met the primary endpoint as second-or third-line treatment for patients with MPM and showed promising efficacy with manageable toxicity. See related commentary by Mansfield and Zauderer, p. 5438

There was a correlation between irAE and efficacy in NSCLC patients treated with nivolumab.

Circulating tumor cells (CTCs), defined as tumor cells circulating in the peripheral blood of patients with solid tumors, are relatively rare. Diagnosis using CTCs is expected to help in the decision-making for precision cancer medicine. We have developed an automated microcavity array (MCA) system to detect CTCs based on the differences in size and deformability between tumor cells and normal blood cells. Herein, we evaluated the system using blood samples from non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients. To evaluate the recovery of CTCs, preclinical experiments were performed by spiking NSCLC cell lines (NCI-H820, A549, NCI-H23 and NCI-H441) into peripheral whole blood samples from healthy volunteers. The recovery rates were 70% or more in all cell lines. For clinical evaluation, 6 mL of peripheral blood was collected from 50 patients with advanced lung cancer and from 10 healthy donors. Cells recovered on the filter were stained. We defined CTCs as DAPI-positive, cytokeratin-positive, and CD45-negative cells under the fluorescence microscope. The 50 lung cancer patients had a median age of 72 years (range, 48–85 years); 76% had NSCLC and 20% had SCLC, and 14% were at stage III disease whereas 86% were at stage IV. One or more CTCs were detected in 80% of the lung cancer patients (median 2.5). A comparison of the CellSearch system with our MCA system, using the samples from NSCLC patients, confirmed the superiority of our system (median CTC count, 0 versus 11 for CellSearch versus MCA; p = 0.0001, n = 17). The study results suggest that our MCA system has good clinical potential for diagnosing CTCs in lung cancer.

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