Complete response with combined BRAF and MEK inhibition in BRAF mutated advanced low-grade serous ovarian carcinoma

Abstract

More effective treatments are needed for low-grade serous ovarian carcinoma (LGSOC). Our patient, who suffers from metastatic LGSOC, had received all established treatments. Sequencing analysis revealed an activating BRAF mutation. Therefore, combined treatment with BRAF and MEK inhibitors, which is the gold standard in malignant melanoma, was initiated. After eight months of therapy, the response was assessed as complete and the treatment is still, 3.5 years after initiation, of benefit. To our knowledge, no complete response on combined BRAF and MEK inhibitor treatment of low-grade serous ovarian cancer has previously been reported.

NOTCH Signaling Limits the Response of Low-Grade Serous Ovarian Cancers to MEK Inhibition

“…This study includes a patient with LGSOC with a durable partial response, emphasizing that the use of the pan-RAFi BGB283 (preferably in combination with trametinib) warrants further testing in LGSOC ( 43 ). Furthermore, a complete response with combined MEKi/BRAFi treatment was recently reported for a patient with advanced LGSOC ( 44 ), further supporting the notion that targeting the MEK and RAF nodes simultaneously may provide a promising treatment strategy. There may be additional clinical implications to the synergy observed using MEKi/pan-RAFi combinations.…”

Impressive and durable clinical responses obtained with dabrafenib and trametinib in low-grade serous ovarian cancer harbouring a BRAF V600E mutation

“…In relation to the BRAF mutation status as a way to select patients to receive treatment with BRAF inhibitors, a basket trial involving vemurafenib reported an anecdotical case of improved response in a patient with LGSOC with V600E BRAF mutation ( Combe et al, 2015 , Hyman et al, 2015 ), and two patients , also with BRAF V600E mutation, included in phase I clinical trials presented durable clinical responses with treatment with dabrafenib (in third line) ( Moujaber et al, 2018 , Falchook et al, 2012 ), and lifirafenib (in second line) ( Moujaber et al, 2018 ). Moreover, we found two case reports of heavily pretreated patients with advanced LGSOC with an activating BRAF mutation that showed a complete and sustained response with combined treatment with dabrafenib and trametinib ( Mendivil et al, 2018 , Tholander et al, 2020 ).…”

“…To our knowledge, to date there are 3 reported cases in the literature of patients with recurrent BRAF V600E mutation-positive LGSOC treated with BRAF inhibitor that presented sustained response ( Moujaber et al, 2018 , Combe et al, 2015 ), and two cases of patients that received combination therapy with BRAF and MEK inhibitor and showed complete clinical response ( Mendivil et al, 2018 , Tholander et al, 2020 ).…”

Durable response to BRAF inhibitor monotherapy in recurrent metastatic low grade serous ovarian cancer

“…Treatment of this patient with a BRAF inhibitor with subsequent durable response contributes to promising evidence of efficacy of targeted therapy in this disease. ( Tholander et al, 2020 ).…”