Histopathological features of complete pathological response predict recurrence-free survival following neoadjuvant targeted therapy for metastatic melanoma
December 23, 2020
Abstract
Background: Recent clinical trials demonstrated the safety and efficacy of neoadjuvant dabrafenib and trametinib (DT) among patients with surgically resectable clinical stage III BRAFV600E/K mutant melanoma. Although patients achieving a complete pathological response (pCR) exhibited superior recurrence-free survival (RFS) versus those who did not, 30% of pCR patients relapsed. We sought to identify whether histopathological features of the pathological response further delineated risk of relapse.
Methods: Surgical resection specimens from DT-treated patients in two phase 2 clinical trials were reviewed. Histopathological features, including relative amounts of viable tumour, necrosis, melanosis, and fibrosis (hyalinized or immature/proliferative) were assessed for associations with patient outcomes.
Results: Fifty-nine patients underwent surgical resection following neoadjuvant DT. Patients achieving pCR (49%) had longer RFS compared with patients who did not (P = 0.005). Patients whose treated tumour showed any hyalinized fibrosis had longer RFS versus those without (P = 0.014), whereas necrosis (P = 0.012) and/or immature/proliferative fibrosis (P = 0.026) correlated with shorter RFS. Multivariable analyses showed absence of pCR or presence of immature fibrosis independently predicted shorter RFS. Among pCR patients, mature/hyalinized-type fibrosis correlated with improved RFS (P = 0.035).
Conclusions: The extent and composition of the pathological response following neoadjuvant DT in BRAFV600E/K mutant melanoma correlates with RFS, including pCR patients. These findings support the need for detailed histological analysis of specimens collected after neoadjuvant therapy.
Source:
M.T. Tetzlaff, C. Adhikari, S. Lo, R.V. Rawson, R.N. Amaria, A.M. Menzies, J.S. Wilmott, P.M. Ferguson, M.I. Ross, A.J. Spillane, K.A. Vu, J. Ma, J. Ning, L.E. Haydu, R.P.M. Saw, J.A. Wargo, H.A. Tawbi, J.E. Gershenwald, G.V. Long, M.A. Davies, R.A. Scolyer, Histopathological features of complete pathological response predict recurrence-free survival following neoadjuvant targeted therapy for metastatic melanoma, Annals of Oncology, Volume 31, Issue 11, 2020, Pages 1569-1579, ISSN 0923-7534, https://doi.org/10.1016/j.annonc.2020.07.016.