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Chemotherapy in patients with metaststic melanoma after progression on BRAF/MEK inhibitorsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Samoylenko I.V., Kharkevich G., Demidov L.V.
- Журнал: Annals of Oncology
- Номер: 27_suppl6
- Год издания: 2016
- Издательство: Oxford University Press
- Местоположение издательства: United Kingdom
- Первая страница: vi379
- Последняя страница: vi400
- DOI: 10.1093/annonc/mdw379.44
- Аннотация: FederationBackground: Metastatic melanoma remains a disease with poor prognosis even inpatients with BRAF mutation, treated by BRAF/MEK inhibitors. In many countriesimmune checkpoints inhibitors which could be used for 2nd line treatment are notregistered, or not reimbursed. At the same time, experimantal evidence supportsenhancing the effectiveness of chemotherapy after blocking the MAP-kinase pathway.We evaluated the immediate effectiveness of chemotherapy in patients afterprogression or intolerance on BRAF/MEK inhibitorsMethods: We conducted a retrospective analysis of all patients (pts) who receivedpaclitaxel 175 mg / m2 day1 + carboplatin AUC= 5 day 1 (PC) from January 1 2012 toMar 30 2016 (n = 55). Group 1 (n = 26) 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 PCResults: Both groups did not differ in demographic characteristics (mean age52.5 ± 12,4 years in group 1 and 53.7 ± 11,6 years respectively, p = 0.5, males 46.1% and58.6% respectively, p = 0.78), the primar y tumor origin (Unknown 15% and 17.2%respectively, skin 85% and 81.8% respectively p> 0.5), or the tumor stage at the start ofchemo (III unresectable 7.6% and 0%, IV M1a 11.5% and 13.6%, IV M1b 15.4% and18.2%, IV M1c 65.3% and 68.2%, respectively, p > 0.5). BRAF mutations rate washigher in Group 1 (96,2% vs 24,1%, p < 0.05). NRAS mutations rate did not differbetween groups (3.8% and 13,8% respectively, p > 0.05). Best overall response rate wascalculated (Table 1). The median time to progression in Group 1 was 16 weeks (95% CI6.12 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 calculatedcorrectly due to short follow-up (median 28 weeks).Table: 1149P Best overall response rateGroup 1, n (%) Group 2, n (%) p valueCR 1 (4) 0 (0) >0.05PR 10 (38) 1 (3.4) >0.05OR 11 (42) 1 (3.4) >0.05SD 5 (19) 3 (10.3) <0.05PD 10 (38) 25 (86.5) p = 0.007Conclusions: MAP-kinase pathway inhibition could enhance effetivenes of subsequentchemotherapy with PC. To evaluate the clinical significance of this observation furtherstudies are needed.Legal entity responsible for the study: Igor SamoylenkoFunding: N N Blokhin Russian Cancer Research Center
- Добавил в систему: Самойленко Игорь Вячеславович