The outcomes of Polish patients with advanced BRAF-positive melanoma treated with vemurafenib in a safety clinical trial

Abstract

Aim of the studyThe BRAF inhibitor vemurafenib has improved progression-free survival and overall survival in patients with BRAFV600-mutation-positive metastatic melanoma. Here we present the results of an open-label safety study with vemurafenib in patients with metastatic melanoma enrolled in Polish oncological centres.Material and methodsPatients with untreated or previously treated Stage IIIC/IV BRAFV600 mutation-positive melanoma were treated with oral vemurafenib in an initial dose of 960 mg twice daily. Assessments for safety and efficacy were made every 28 days. For the survival analysis the Kaplan-Meier estimator was used with the log-rank tests for bivariate comparisons.ResultsIn total, 75 Polish patients were enrolled in the safety study across four centres. At data cut-off, 28 patients died (37%), mainly (26) due to disease progression; 33 (44%) patients continued vemurafenib after disease progression. The objective response rate was 46%, including two patients with a complete response and 29 with a partial response. Median progression-free survival was 7.4 months. The one-year overall survival rate was 61.9% (median overall survival was not reached). Seventy-three (97.3%) patients reported adverse events (AEs), and grade 3–5 toxicity was reported in 49.4% (37) patients. The most common AEs were: skin lesions (including rash and photosensitivity), arthralgia, and fatigue.ConclusionsThe overall safety profile and response rate of vemurafenib were comparable to those reported in previous studies of this drug. Our study confirmed the value of well-established prognostic features for overall survival, such as initial LDH (lactate dehydrogenase) level and AJCC staging.

Real-world treatment practice in patients with advanced melanoma

“…In our study, 43% ORR and 77% DCR were noted, and 19% ORR and 65% DCR were recorded in the 1995-2005 study. All the results obtained in our study are comparable with the treatment outcomes via new therapies in other centres in Poland [15][16][17][18] and other studies with real-world data [19][20][21][22].…”

Plasma lncRNA expression profile as a prognostic tool in BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor

“…These patients can be treated with BRAF inhibitors (vemurafenib or dabrafenib) alone or in combination with MEK inhibitors (cobimetinib or trametinib), which is the currently recommended treatment plan. The objective response rate (CR and PR) is observed in 50% to 70% of patients; however, about half of them will develop resistance to the treatment after 6 to 11 months of therapy [3, 5, 21, 23].…”

Wyniki leczenia wemurafenibem chorych na zaawansowanego czerniaka w ramach programu lekowego w Polsce

“…Korzyść z leczenia mają chorzy niezależnie od wieku, płci, stopnia sprawności, linii leczenia systemowego, obecności przerzutów do OUN, stopnia zaawansowania czy aktywności LDH [8,9], część z tych czynników wpływa jednak na dłuższe PFS i OS podczas terapii wemurafenibem. Mediana PFS wynosząca około 7 miesięcy i OS około roku w naszej grupie chorych leczonych w ramach programu lekowego jest zbliżona do danych opublikowanych w badaniu bezpieczeństwa terapii na 3222 chorych, z czego połowa otrzymała już wcześniej leczenie systemowe z powodu zaawansowanego czerniaka [9,10]. Obecne wskaźniki przeżyć przy leczeniu wemurafenibem są około dwa razy wyższe niż wcześniej obserwowane w grupie zaawansowanych chorych z obecnością mutacji BRAF [11].…”