Distribution and frequencies of BRAF mutations in patients with advanced melanoma in Southern Germany

Hintergrund: Bei Patienten mit fortgeschrittenem Melanom gilt die Analyse des Vorhandenseins einer BRAF-Mutation als obligatorisch, bevor eine teure Behandlung mit BRAF/MEK-Inhibitoren eingeleitet wird. Manchmal ist es jedoch schwierig, eine solche Analyse durchzuführen, wenn kein archivierbares Tumorgewebe vorhanden ist und frisches Gewebe entnommen werden muss. Methoden: Wir sammelten den klinischen und mutationsbedingten Status von 1170 Patienten mit fortgeschrittenem Melanom und etablierten drei verschiedene prädiktive Modelle (binäre logistische Regression, Klassifikations- und Regressionsbäume, zufälliger Wald), um den BRAF-Status vorherzusagen. Ergebnisse: 514 von 1170 Patienten (44%) trugen eine BRAF-Mutation. Alle Modelle zeigten Alter und histologischen Subtyp des Melanoms als die beiden wichtigsten prädiktiven Variablen. Die Genauigkeit lag zwischen 0,65-0,71 und war damit am besten im zufälligen Waldmodell. Die Empfindlichkeit lag bei 0,76- 0,84, wiederum am besten im Zufallswaldmodell. Die Spezifität war in allen Modellen im Bereich von 0,51-0,55 gering. Fazit: Mit Hilfe modernster statistischer Modelle konnten wir BRAF-Mutationen nicht in einem akzeptablen Umfang vorhersagen. Die Analyse des Mutationsstatus durch Sequenzierung oder Immunhistochemie ist weiterhin als Standard der Versorgung anzusehen

Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma

Background: Ipilimumab is an approved immunotherapy that has shown an overall survival benefit in patients with cutaneous metastatic melanoma in two phase III trials. As results of registrational trials might not answer all questions regarding safety and efficacy of ipilimumab in patients with advanced melanoma seen in daily clinical practice, the Dermatologic Cooperative Oncology Group conducted a phase II study to assess the efficacy and safety of ipilimumab in patients with different subtypes of metastatic melanoma. Patients and methods: We undertook a multicenter phase II study in melanoma patients irrespective of location of the primary melanoma. Here we present data on patients with pretreated metastatic cutaneous, mucosal and occult melanoma who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs),including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months. Results: 103 pretreated patients received at least one dose of ipilimumab, including 83 cutaneous, seven mucosal and 13 occult melanomas. 1-year OS rates for cutaneous, mucosal and occult melanoma were 38 %,14 % and 27 %,respectively. Median OS was 6.8 months (95 % CI 5.3-9.9) for cutaneous, 9.6 months (95 % CI 1.6-11.1) for mucosal, and 9.9 months (lower 95 % CI 2.3, upper 95 % CI non-existent) for occult melanoma. Overall response rates for cutaneous, mucosal and occult melanoma were 16 %,17 % and 11 %,respectively. Eleven patients had partial response (16 %) and ten patients experienced stable disease (14 %),none achieved a complete response. Treatment-related AEs were observed in 71 patients (69 %),including 20 grade 3-4 events (19 %). No new and unexpected safety findings were noted. Conclusions: Ipilimumab is a treatment option for pretreated patients with advanced cutaneous melanoma seen in daily routine. Toxicity was manageable when treated as per protocol-specific guidelines

Which melanoma patient carries a BRAF-mutation? A comparison of predictive models

Background: In patients with advanced melanoma the detection of BRAF mutations is considered mandatory before the initiation of an expensive treatment with BRAF/MEK inhibitors. Sometimes it is difficult to perform such an analysis if archival tumor tissue is not available and fresh tissue has to be collected. Results: 514 of 1170 patients (44%) carried a BRAF mutation. All models revealed age and histological subtype of melanoma as the two major predictive variables. Accuracy ranged from 0.65-0.71, being best in the random forest model. Sensitivity ranged 0.76-0.84, again best in the random forest model. Specificity was low in all models ranging 0.51-0.55. Methods: We collected the clinical data and mutational status of 1170 patients with advanced melanoma and established three different predictive models (binary logistic regression, classification and regression trees, and random forest) to forecast the BRAF status. Conclusions: Up to date statistical models are not able to predict BRAF mutations in an acceptable accuracy. The analysis of the mutational status by sequencing or immunohistochemistry must still be considered as standard of care

MOESM3 of Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma

Additional file 3: Table S3. Patients with different response pattern in intracranial and extracranial metastases