Paclitaxel and carboplatin chemotherapy in patients with metaststic melanoma refractory to BRAF/MEK inhibitors.

9552 Background: Metastatic melanoma remains a disease with poor prognosis even in patients with BRAF mutation, treated by BRAF/MEK inhibitors. In many countries immune checkpoints inhibitors which could be used for 2nd line treatment are not registered, or not reimbursed. At the same time, experimantal evidence supports enhancing the effectiveness of chemotherapy after blocking the MAP-kinase pathway. We evaluated the immediate effectiveness of chemotherapy in patients after progression or intolerance on BRAF/MEK inhibitors. Methods: We conducted a retrospective analysis of all patients (pts) who received paclitaxel 175 mg / m2 day1 + carboplatin AUC = 5 day 1 (PC) from January 1 2012 to December 30 2015 (n = 51). Group 1 (n = 22) was treated with BRAF / MEK inhibitors (vemurafenib, dabrafenib, trametinib, encorafenib or binimetinib) before PC, group 2 (n = 29) received no inhibitors of BRAF / MEK prior to PC. Results: Both groups did not differ in demographic characteristics (mean age 51.5 ± 12,7 years in group 1 and 53.9 ± 11,5 years respectively, p = 0.5, males 54.5% and 58.6% respectively, p = 0.78), the primary tumor origin (Unknown 18.2% and 17.2% respectively, skin 79.3% and 81.8% respectively p> 0.5), or the tumor stage at the start of chemo (III unresectable 6.9% and 0%, IV M1a 10.3% and 13.6%, IV M1b 17.2% and 18.2%, IV M1c 65.5% and 68.2%, respectively, p>0.5). BRAF mutations rate was higher in Group 1 (95,5% vs 24,1%, p<0.05). NRAS mutations rate did not differ between groups (4,5% and 13,8% respectively, p>0.05). Best overall response rate was calculated (Table 1). The median time to progression in Group 1 was 15 weeks (95% CI 6.12 to 23.87 months) and 7.0 weeks (95% CI 5.17 to 8,28) in Group 2; p = 0.019, HR = 2,14 (95% CI 1.08 to 4.21). The median overall survival can not be calculated correctly due to short follow-up (median 25 weeks). Conclusions: MAP-kinase pathway inhibition could enhance effetivenes of subsequent chemotherapy with PC. To evaluate the clinical significance of this observation further studies are needed. Best overall response rate. Group 1, n(%) Group 2, n(%) P CR 1 (4.5%) 0 >0.05 PR 8 (36.4%) 1 (3.4%) <0.05 OR 9 (40,9%) 1 (3.4%) <0.05 SD 3 (13.6%) 3 (10.3%) >0.05 PD 10 (45.5%) 25 (86.5%) p = 0.007