Subacute cutaneous lupus erythematosus following ribociclib therapy for metastatic breast cancer.

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.

Real-world outcomes of abiraterone and enzalutamide in first-line treatment of metastatic castration-resistant prostate cancer: which patients benefit most?

OBJECTIVES: Abiraterone and enzalutamide are two oral novel androgen receptor axis-targeted agents approved for the treatment of castration-resistant prostate cancer (mCRPC). Despite the availability of multiple treatments, there is a need to improve the knowledge and management of these drugs in the real-world setting, especially in patient groups under-represented in clinical trials. Our aim was to review the outcome of patients with chemotherapy-naïve mCRPC treated with abiraterone or enzalutamide in routine clinical practice in order to identify factors that are predictive for response. METHODS: This observational retrospective study was performed in a Spanish tertiary hospital and included men with chemotherapy-naïve mCPRC who started treatment with abiraterone or enzalutamide between September 2012 and November 2018. The study end date was 30 October 2020. RESULTS: Ninety patients with mCRPC were included, 57 with abiraterone and 33 with enzalutamide. Median overall survival (OS) was 26.87 months (95% CI 19.68 to 34.05), with no difference found between the two treatment groups. Nine variables were related to increased OS in the univariate analysis: Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs 2), pain (need of opioids for cancer pain), visceral disease, ≥3 bone lesions, exclusively lymph node metastases, baseline prostate specific antigen (PSA) (<50 vs ≥50 ng/dL and <20 vs ≥20 ng/dL), haemoglobin (<12 vs ≥12 g/dL) and alkaline phosphatase (≤116 vs >116 IU/L). A PSA response >50% was observed in 65 patients (76.5%). In the multivariate analysis, ECOG performance status, pain, visceral disease and alkaline phosphatase provided independent prognostic information. Median OS by Kaplan-Meier analysis was significantly longer for patients with a PSA response (32.1 vs 17.9 months; HR 0.46, 95% CI 0.27 to 0.78; p=0.003). CONCLUSIONS: This study assessed the efficacy of abiraterone and enzalutamide in a real-world setting, including patients under-represented in pivotal studies. Some clinical factors were correlated with improved OS in chemotherapy-naïve men with mCPRC treated with these drugs.

MiRNAs in renal cell carcinoma

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer. (AU)

MiRNAs in renal cell carcinoma.

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer.

Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study.

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.

mTOR pathway inhibition in renal cell carcinoma.

Renal cell carcinoma therapy has changed in a very significant way in the last few years. Up to 5 new agents have been developed, improving the results previously achieved with cytokine therapy. Bevacizumab, sorafenib, sunitinib, temsirolimus, and everolimus are now part of the therapeutic arsenal for this illness. Particularly, this has been the first tumoral type in which inhibition of mammalian target of rapamycin (mTOR) has proved its efficacy in phase III trials, either as first-line therapy for poor prognosis patients (temsirolimus, CCI-779) or as second-line therapy after failure of tyrosine-kinase inhibitors (everolimus, RAD001). In this paper, we review the basis for mTOR inhibition in RCC, and discuss the results of the trials involving temsirolimus and everolimus for the treatment of this disease.

MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients.

Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting.

Intra-abdominal desmoplastic small round cell tumour in a 39-year-old man.

Desmoplastic small round cell tumor is a very rare neoplasm, that usually appears in children and young adolescents. There is no standard therapy, and responses to chemotherapy are infrequent. Surgery is still the main treatment for this disease. We report the case of a 39 year-old man and briefly summarize the evidence about this tumor.

Epidemiologic study to assess patient involvement in choice of adjuvant chemotherapy for breast cancer (PROSA Study).

INTRODUCTION: The objective of the current study was to assess patient involvement in adjuvant chemotherapy choice, reasons for treatment choice and satisfaction with the chosen treatment, given that improvement in breast cancer survival has been accompanied by a greater demand for disease information from patients. MATERIAL AND METHODS: An epidemiologic, prospective, multicentre study was conducted with patients aged over 18 diagnosed with breast cancer stages I, II and III. The study, which was conducted prior to these patients initiating adjuvant chemotherapy, was based on a baseline visit and a follow-up visit. Data on sociodemographic and clinical variables were collected and a survey was administered to assess both the reasons for choosing particular treatments and ultimate satisfaction with the chosen treatment. Statistical procedures included a descriptive analysis, bivariate tests and logistic regression. RESULTS: A total of 613 patients were recruited with a mean (SD) age of 53.3 (10.8) years. Most patients had stage II breast cancer (53.9%) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (82.8%). Of these patients, 58.3% were treated with taxanes (48.2% docetaxel, doxorubicin and cyclophosphamide) and 41.7% without (43.5% 5-fluorouracil, epirubicin and cyclophosphamide). At the baseline visit and final visit, 73.8% and 72.6% of patients, respectively, were aware of their diagnosis and prognosis. A total of 77.1% patients (64.7% who had followed their physician's advice) were involved in treatment choice and this involvement was directly related to improved ECOG performance status and information. A total of 78.7% of patients were very satisfied or satisfied with their treatment and 5.4% of patients refused to continue treatment (with 39.3% giving toxicity as the reason). CONCLUSIONS: Although a high proportion of patients were involved in choosing their treatment, this involvement was not related to greater treatment satisfaction. Further research in routine clinical settings is needed in order to assess other factors related to choice of adjuvant chemotherapy, treatment satisfaction and long-term effectiveness (3-5 years).

Cirrhosis-like radiological pattern in patients with breast cancer.

INTRODUCTION: Hepatic toxicity of breast cancer therapy is well known, usually consisting of elevation in the serum levels of hepatic enzymes or fatty infiltration of the liver. The chemotherapeutic agents most commonly linked to hepatotoxic effects are methotrexate, anthracyclines, taxanes and cyclophosphamide. There are few reports of patients with liver metastasis having radiological findings mimicking cirrhosis, both in the presence or the absence of prior systemic chemotherapy. Hepatotoxicity of antineoplastic drugs and cellular necrosis induced by response of liver metastases to chemotherapy may play a critical role in its physiopathology. MATERIALS AND METHODS: This article reports a series of ten women with breast cancer (nine with liver metastasis) treated with chemotherapy or hormonotherapy. RESULTS: They had low risk factors for hepatic disease, but developed a cirrhosis-like appearance in the computed tomography scan. The patient without liver metastasis is the second of this kind described in the literature. Relatively few reports have documented clinical sequelae of portal hypertension. In our series, three patients had oesophageal bleeding varices needing be hospitalised. To our knowledge, these are the first cases reported in the literature. CONCLUSIONS: This suggests that some manifestations of portal hypertension may develop in association with the cirrhosis- like pattern induced by breast cancer therapy.