As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.

BACKGROUND: Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium‐labeled octreotide (¹¹¹In‐DTPA‐D‐Phe¹‐octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study.METHODS: Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow‐up). In 8 cases, octreotide was replaced by the long‐acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated.RESULTS: The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow‐up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients).CONCLUSIONS: Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long‐acting analog lanreotide, which requires fewer injections, improves patients' compliance. Cancer 2002;94:1414–20. © 2002 American Cancer Society.DOI 10.1002/cncr.10374

Background: No previous prospective trials have been reported with capecitabine and gemcitabine (CAP-GEM) in patients with metastatic thymic epithelial tumors (TETs). We conducted a multicenter study to determine the activity and tolerability of this regimen in pretreated TETs. Patients and methods: A total of 15 patients were enrolled in the first stage of phase II study. All patients received CAP-GEM every 3 weeks. The primary end point was objective response rate (RR); secondary end points were toxicity, progression-free survival (PFS) and overall survival. Results: Complete responses (CR) and partial responses were observed in three (20%) and three (20%) patients for a 40% RR, respectively. Grade 1–2 neutropenia, anemia and thrombocytopenia were the most common side-effects, noted in seven (46.7%), five (33.3%) and five (33.3%) patients, respectively. The most common grade 3 toxicity was neutropenia in three patients (20%). Median PFS was 11 months (95% confidence interval 4–17). The 1- and 2-year survival rates were 80% and 67%, respectively. Conclusion: We have decided to publish the preliminary results because this regimen was more active than that expected. Although our results are preliminary, CAP-GEM shows activity and safety in pretreated TETs. Furthermore, multicenter trials, also in first-line setting, are necessary to confirm our results.

The therapeutic approach to advanced or metastatic solid tumors, either with chemotherapy or targeted therapies, is mainly palliative. Resistance to chemotherapy occurs very frequently and is one of the most important reasons for disease progression. Immunotherapy has the potential to mount an ongoing, dynamic immune response that can kill tumor cells for an extended time after the conventional therapy has been administered. Such a long-lasting response is potentially able to completely eradicate tumor cells, rather than producing only a temporary killing of cells. The most promising immune-based treatments are monoclonal antibodies that act as checkpoint inhibitors (e.g. ipilimumab and nivolumab), adoptive cell therapy (e.g. T-cells expressing chimeric antigen receptors) and vaccines (e.g. sipuleucel-T). Ipilimumab is currently approved for the treatment of metastatic melanoma and sipuleucel-T is approved for advanced prostate cancer. There is great interest in immunotherapy in other solid tumors, potentially used alone or in a multimodal fashion with chemotherapy and/or biological drugs. In this paper, we review recent advances in immuno-oncology in solid malignancies (except melanoma) as were discussed at the inaugural meeting of the Campania Society of Oncology Immunotherapy (SCITO).