The recent pan-cancer NTRK inhibitor approval placed molecularly targeted therapies and biomarker testing back in the spotlight. horizon scanning for approaching approvals is helpful in planning future treatments and ensuring the appropriate biomarker testing is in place.
[Prevalence by cancer type: emerging therapeutic biomarkers]
THE RET INHIBITOR selpercatinib is FDA approved for NSCLC and thyroid cancers harbouring RET fusions(UK NICE assessment due June 2021). RET fusions are found at low prevalence in many solid tumours, andbasket studies are in progress.
THE FGFR INHIBITORS pemigatinib and erdafitinib are FDA approved for cholangiocarcinoma and bladdercancer respectively (UK NICE assessment to be confirmed). Responses to inhibition of the FGFR axis havebeen reported in other tumour types harbouring FGFR fusions and basket studies are on-going.
THE KRAS G12C INHIBITOR AMG 510 generated interest in early clinical development, showing activity againsta target previously thought be to undruggable. More recent clinical data have been a little disappointing butstill one to watch, with on-going studies focussed on NSCLC and colorectal cancer alongside basket studies.
Tumours harbouring BRAF V600 MUTATIONS continue to generate interest, with vemurafenib (a BRAF inhibitor) showing activity against 13 different tumour types in a recent basket study.
THE IDH1 INHIBITOR ivosidenib is FDAapproved for the treatment of acutemyeloid leukaemia, and has shown promise in cholangiocarcinoma with phaseIII trials on-going. Clinical studies are atan early stage for IDH-mutant CNS tumours.
THE AKT INHIBITORS capivasertib andipatasertib have shown promise in AKTE17 mutant breast cancer and PTENdeficient prostate cancer respectively. Studies in other tumour types are on-going.
