Switch to checkpoint inhibition after targeted therapy at time of progression or during on-going response: a retrospective single centre experience in patients with BRAF mutated melanoma.

Switch to checkpoint inhibition after targeted therapy at time of progression or during on-going response: a retrospective single centre experience in patients with BRAF mutated melanoma.

Publication date: Oct 23, 2019

BRAF+MEK inhibition is preferentially applied as first line therapy in BRAF V600 mutated melanoma patients with unfavourable prognostic features, due to the ability of targeted therapy (TT) to induce rapid symptom control, decrease tumour burden, and normalize lactate dehydrogenase (LDH) levels. In addition, short-term TT transiently increases tumour antigen presentation and tumour influx of T-cells. Therefore, it might be favourable to switch TT to checkpoint inhibition (CPI) before progression (PD).We retrospectively analysed melanoma patients treated first line with TT (TT1) and who subsequently switched to CPI during response to TT (sDR-group) or at progression upon TT (sPD-group). We identified 74 patients (n = 37 sDR-group and n = 37 sPD-group). ORR to CPI was 27.0% in the sDR-group versus 24.3% in the sPD-group (p = 0.790). Median was PFS 2.5 months versus 1.2 months (p = 0.145), and median OS was 30.6 versus 14.1 months (p = 0.007). After adjusting for baseline differences and known prognostic factors, hazard ratio’s (HRs) favouring sDR were 0.89 for PFS upon CPI (p = 0.956) and 0.48 for OS (p = 0.055). Thus, patients switching to CPI during on-going clinical benefit from TT do not have an inferior outcome. Due to baseline imbalances and small patient population, a favourable trend for the sDR-group can be hypothesized only.

Reijers, I.L.M., Rozeman, E.A., Wilgenhof, S., van Thienen, J.V., Haanen, J.B.A.G., and Blank, C.U. Switch to checkpoint inhibition after targeted therapy at time of progression or during on-going response: a retrospective single centre experience in patients with BRAF mutated melanoma. 24553. 2019 Pigment Cell Melanoma Res.

Concepts Keywords
Antigen Presentation SPD
BRAF SDR
CPI SDR group sPD
Lactate Dehydrogenase Tumour
LDH Medicine
Median Clinical medicine
MEK Immune system
Melanoma Cancer treatments
Pigment Antineoplastic drugs
SPD Melanoma
Symptom Checkpoint inhibitor
T Cells Targeted therapy
Targeted Therapy BRAF
Tumour MEK inhibitor

Semantics

Type Source Name
gene UNIPROT RPL17
gene UNIPROT CTLA4
gene UNIPROT HGS
gene UNIPROT SRSF5
gene UNIPROT HARS
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT BRAF

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