DISCUSSION
The Cancer Genome Atlas (TCGA) dataset manifests 432 cases of gastric
cancer (SC) harbouring FGFR3 amplification wherein 24 cases showed copy
number gain and 12 cases with copy number loss. Imran et al. have
discussed the originating mutational events at the gene level and the
corresponding consequence in tumour formation and
progression.13
A case study reported in a patient diagnosed with urothelial cancer was
treated with pazopanib whose FFPE tumor harboured amplification of FGFR3
(11 copies), CCND1 (21 copies), and FGF19 (21 copies), and FGFR3
p.(S249C) mutation with estimated mutant allele frequency of 58%. The
patient showed partial response followed by stable disease to the
targeted therapy given.9 Another study by Kim et al.
has reported a gastric cancer patient with liver metastases who
harboured FGFR3-TACC3 novel fusion which is extremely rare in
gastrointestinal cancer.14 In this case study, the NGS
analysis of the tumor sample had revealed FGFR3 gene amplification with
10 copies. Pazopanib is widely known to exert its action against VEGFR1,
VEGFR2, VEGFR3, PDGFRα and β, FGFR1, FGFR3, c-KIT, LCK, and macrophage
colony-stimulating factor-1 receptor. Seung Kim et . alstated that FGFR2 expression by IHC might be a useful biomarker for
predicting treatment outcomes of patients with metastatic or recurrent
advanced Gastric cancer treated with Pazopanib in combination with
Capecitabine and Oxaliplatin.11 Dovitinib, an FGFR
inhibitor under phase II cancer trial is useful against FGFR3-mutated or
overexpressed urothelial cancer.15 The FiGhTeR trial
is a phase II, single-arm, open-label study to assess safety and
activity of the FGFR inhibitor pemigatinib as second-line treatment
strategy in metastatic EGJ/GC patients progressing under
trastuzumab-containing therapies.16 Pazopanib is
approved for use in advanced renal cell cancer and soft tissue sarcoma
patients who have received prior chemotherapy. Under the Phase II study
of the Arbeitsgemeinschaft internistische Onkologie (AIO) trial,
pazopanib along with 5-fluorouracil, leucovorin, and oxaliplatin (FLO)
is known to show promising outcome in advanced gastric
cancer.17 Pazopanib plus fluoropyrimidine and platinum
combination in the first line setting in gastric cancer showed that
median OS ranged from 10.1 months to 10.5 months under prospective phase
II trial of
pazopanib.18
Although Trastuzumab is SoC in gastric cancers with HER2 overexpression
(IHC), the same could not be evaluated in this patient due to sample
insufficiency. This conundrum is often experienced in the clinical
setting where IHC analysis of relevant biomarkers is impeded due to
sample insufficiency or non-representative sampling. Though HER2
amplification was not observed on NGS, and HER2 status could not be
ascertained on IHC, NGS profiling successfully identified an alternate
therapeutically targetable indication, i.e., FGFR. Patient showed
sustained response to treatment over the treatment duration leading to
significant regression of the metastatic lesions.
The combination of Gemcitabine and Pemetrexed has been evaluated in
Advanced Non-Small Cell lung Cancer with myelosuppression, especially
neutropenia, as a significant adverse event.19,20
However, in the present case, apart from transient Grade III
Thrombocytopenia and other transient AEs, there were no other
significant or myelosuppressive AEs indicating the safety of the
treatment regimen.