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.