A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterised by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity. PATIENTS AND METHODS: PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200 mg/Q3W) versus institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0-1 and unselected for programmed cell death ligand 1 (PD-L1) status. At progression, patients randomly assigned to receive chemotherapy were allowed to crossover to pembrolizumab. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary end points were overall survival (OS), investigator-assessed PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses. RESULTS: Between September 2017 and August 2018, 144 patients were randomly allocated (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20 February 2019, median follow-up of 11.8 months (interquartile range: 9.9-14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected [hazard ratio = 1.06, 95% confidence interval (CI): 0.73-1.53; P = 0.76], and median BICR-PFS (95% CI) for pembrolizumab was 2.5 (2.1-4.2), compared with 3.4 (2.2-4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95% CI: 13% to 33%), over chemotherapy (6%, 95% CI: 2% to 14%; P = 0.004). Forty-five patients (63%) assigned to chemotherapy received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: (14.8-19.7)], no difference in OS was detected between groups (HR = 1.12, 95% CI: 0.74-1.69; P = 0.59), even after adjusting for crossover. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS. CONCLUSION: This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy.

Expression profiling of breast tumors based on human epidermal growth factor receptor 2 status defines migration-related genes.

OBJECTIVE: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative breast cancer tumors remain unclear. The aim of this study was to identify a gene expression profile for breast tumors based on their HER2 status. METHODS: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. RESULTS: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, other genes located on 17q12 and genes functionally related to migration. CONCLUSION: Our study shows the potential of integrated genomic profiling to shed light on the molecular knowledge of HER2-positive breast tumors.

SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020).

Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.

Intraocular metastasis as a systemic presentation of neuroendocrine differentiation of prostate carcinoma.

A 68 year-old male was referred for assessment of an amelanotic lesion in the right eye (RE) that was associated with a gradual loss of visual acuity (VA), of 2 months onset, as the main symptom. It was noted in his medical history, that 6 years ago, he had prostate cancer treated with prostatectomy, lymphadenectomy, and coadjuvant local radiotherapy (RT). He was asymptomatic until 6 months ago, when a metastasis was discovered in the left femur, which was treated with radiotherapy. There were no findings of interest in the left eye (LE). His AV was very low in his RE, and in the eye fundus examination a mass without pigment was observed in the posterior pole with an adjacent exudative retinal detachment. Due to his personal history and results of the complementary tests such as ultrasound and magnetic resonance, the most likely diagnostic option was metastasis of prostate carcinoma, subsequently being confirmed with the histopathology results. Despite 4 cycles of chemotherapy, the patient did not show any clinical or radiological response, worsening until his death 3 months later.

Efficacy of tyrosine kinase inhibitors in EGFR-mutant lung cancer women in a real-world setting: the WORLD07 database.

BACKGROUND: The WORLD07 project is a female specific database to assess the characteristics of women with lung cancer. METHODS: WORLD07 database sets up in 2007, and prospectively stores clinical characteristics, treatment, outcome, and follow-up of lung cancer women. All women with epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) were selected for this analysis. RESULTS: From October 2007 to December 2012, a total of 1775 NSCLC women were recruited. EGFR mutation was identified in 34.4% of patients. Upfront EGFR tyrosine kinase inhibitor (TKI) reported a response rate of 60%, a median progression-free survival of 11.7 months, and median overall survival of 23.0 months. EGFR TKI, EGFR-mutation type, and smoking status did not impact in the outcome of treated women. CONCLUSION: Prevalence of EGFR mutation in women with NSCLC is higher than overall population with NSCLC. Efficacy of EGFR TKI in this real-world setting is similar to that previously reported.