Advancement in technology has led to deeper analysis of treatment refractory solid tumours by molecular sequencing with a hope to identify patients who get benefited with newer novel targeted therapies. We aim to study the impact of CGA in solid tumour to detect actionable mutations.
A retrospective study of all patients with stage IV solid malignancies who underwent CGA at The Brunei Cancer Center (TBCC), PJSC between January 2019 – March 2022 were included. Both tissue and liquid based samples were analyzed, all patients had disease progression on two lines of treatment at the time of biopsy.
Out of 197 samples sent, 174 had good quality tissue for analysis. 71with liquid biopsy and 103 tissue based. 57.4% (n=100) of patients had actionable mutation or druggable target defined as a genomic alteration for which an FDA approved drug was available for a particular cancer type or in other cancer subtypes. On including TMB>10 or PDL1 + on IHC for initiating immunotherapy, 74.1% (n=129) had a druggable target. On discussion in the molecular MDT, 34.1%(n=44) received targeted therapy. NSCLC adenocarcinoma 27.5 % (n=48) and Breast 24.7% (n=43) were commonest followed by MCRC 10.9% (n=19), Sarcomas including osteosarcoma/STS/MPNST/LMS 5.1% (n=9), CUP 4.5%(n=8), Cholangiocarcinoma 4%(n=7), Ovary 3.4%(n=6), HNSCC, Pancreas and Stomach 2.8%(n=5) each, NPC 2.2%(n=4), Endometrium and Prostate 1.7%(n=3) each, Brain, Cutaneous SCC, Cervix and PNET 1.1%(n=2) each and Rectum 0.5%(n=1). In NSCLC, the median TMB was 8.5 (range 0-53), average number of alterations varied between 0-12. Most were EGFR exon 19 deletion, PIK3CA (E542Q- 7, E545K-2, K111del-5), KRAS (G12D-6, G12C-3), BRCA1,2 and MET alterations. In MBC, the median TMB was 4.5 (range 0-18), average alterations detected were between 0-16, majority had ESR1 mutation, PIK3CA (E545K-4, K111del-2, H1047R-3), NF1, BRCA2 and FGFR alteration. MSI – H (1.1%) was noted only in 2. In patients with TMB>7, there were increased actionable alterations detected (p<0.05).
CGA helps in detecting druggable targets in majority of patients, due to availability of most targeted agents in our country, majority of patients could receive the approved druggable target. CGA and targeted therapy should be made more affordable, as many can be benefitted.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.