Real-world safety profile of abiraterone acetate in patients with castration-resistant prostate cancer and cardiovascular comorbidities: a retrospective, single center study

Background: Abiraterone acetate became a referral treatment for metastatic castration-resistant prostate cancer (mCRPC) in a post-docetaxel setting despite a remarkable percentage of cardiovascular adverse events (AEs). As a consequence, the evaluation of cardiovascular safety in patients at risk should be mandatory. We aimed to assess the cardiovascular safety of abiraterone acetate in a real-world series of mCRPC patients treated at our institution. Materials and Methods: We retrospectively included mCRPC patients with at least 1 active cardiovascular comorbidity or risk factor according to the European Society of Cardiology (ESC) guidelines and who started treatment with abiraterone acetate from April 2011 to July 2012. Cardiac assessment with electrocardiogram and echocardiogram was performed at baseline and at treatment discontinuation. AEs were defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Statistical analyses were performed by descriptive statistics as appropriate. Results: We included 51 patients of whom 18% had an ESC score risk for a major cardiovascular event ≥4%. At a median follow-up of 36 months, no cardiac AEs (rhythm abnormalities or left ventricular function decrease) were observed. The most frequent grade 1-2 AE reported was fluid retention (18%) followed by hypertension and asthenia (16%). The most frequent grade 3-4 AEs were asthenia and pruritus/rash. No patients discontinued abiraterone because of toxicity. Conclusions: Abiraterone acetate showed a favorable safety profile in mCRPC patients with cardiovascular comorbidities or risk factors in a post-docetaxel setting, but further studies are needed to confirm our findings and to explore other settings of disease.

Secondary de-bulking surgery in recurrent ovarian cancer

No abstract available

Immunotherapy and non-small cell lung cancers

Lung cancer is the leading cause of cancer mortality, and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Immunotherapy has brought a paradigm shift to the treatment of NSCLC. Immune checkpoint inhibitors have emerged as one of the main new therapeutic options for patients with advanced NSCLC. This brief review focuses on analyzing the biological rationale and early clinical data available concerning immunotherapeutic strategies, and more specifically, programmed cell death-1 (PD-1) inhibitors and programmed cell death-ligand 1 (PD-L1) inhibitors.

Predictive biomarkers of response for PD-1/PD-L1 inhibitors: a cumbersome gold rush

Programmed cell death protein 1 (PD-1) and its ligand programmed cell death-ligand 1 (PD-L1) are overexpressed in a number of human malignancies. More interestingly, their expression has been associated with patient survival in non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, esophageal, pancreatic and colorectal carcinoma, with the data commonly suggesting a negative prognostic role. In this review, we summarize the pros and cons regarding the predictive role of PD-L1 expression in candidate patients for checkpoint inhibitors. Furthermore, we discuss the potential predictive role of other biomarkers, such as tumor mutational burden, microsatellite instability, mismatch repair deficiency and tumor infiltrating lymphocytes. We conclude that PD-L1 testing probably represents simply a “snapshot” of an intricate, fluctuating and dynamic process, that in turn represents the interplay between the immune system and cancer. The PD-L1 assay can be considered more useful for response stratification than in patient selection.

Case 2 – Adjuvant therapy in a patient with HER2-positive early breast carcinoma

Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2), which represents an adverse prognostic factor. The therapeutic landscape for this type of breast cancer has been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Despite that, some of these patients will eventually relapse. Dual HER2 blockade has been successfully tried in early and advanced breast cancer. Here we report the case of an early HER2-positive breast cancer patient treated with trastuzumab, pertuzumab, and chemotherapy. The recently released final results of the much anticipated APHINITY trial confirm the outcome achieved in this patient.

New treatment opportunities for patients with advanced and/or metastatic thyroid cancer

No abstract available

SRSF2 mutations in epithelial ovarian cancer

Resistance to platinum chemotherapy regimens represents a major obstacle in the successful treatment of epithelial ovarian cancer (EOC) patients. Among the molecular mechanism responsible for resistance to platinum, alternative splicing, which is induced upon platinum treatment, can control apoptosis by regulating the expression of apoptotic protein variants with opposite functions. Alterations in alternative splicing are found in tumors and can hinder apoptotic response. In the present study we sequenced SRSF2, a splicing factor that regulates Caspase-8 and Caspase-9 variants, in search of mutations that could possibly explain alternative mechanisms of platinum resistant in EOC.

Letter to the Editor

No abstract available

Case 1 – Successful resection after FOLFIRI plus cetuximab therapy for unresectable colorectal cancer with multiple liver metastases

This case report describes the outcome of a multidisciplinary approach which allowed successful resection in a patient diagnosed with unresectable colorectal cancer. The patient was a 66-year-old man with no important comorbidities. His main complaint was abdominal pain. The patient received a diagnosis of moderate differentiated sigmoid colon adenocarcinoma, RAS and BRAF wild type. Multiple liver metastases were detected. Conversion therapy was given and the patient received 8 therapy courses with FOLFIRI plus cetuximab. Grade 1 diarrhea and grade II skin toxicity were observed as adverse effects of the chemotherapy. The size of the tumor was reduced and the tumor was resected performing left colectomy, segment liver VI resection and performing intraoperative thermos-ablation with microwave. No recurrence was observed at 6 months after surgery.

Trial designs for the development of new drugs

No abstract available