The rate of BRAF mutation in our cohort (28.8%) was lower than international published rates of 40%-60%. This may reflect ethnic or geographic differences within population cohorts. The high concordance rate of PCR and immunohistochemical methods in determining BRAF status suggests that immunohistochemistry is potentially a viable, cost-effective alternative to PCR testing and suitable as a screening test for the BRAF mutation.
The poor prognosis for patients with esophagogastric cancers (EGC) has resulted in an increased focus on the use of targeted agents in this disease. Targets include epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), Her2, mammalian target of rapamycin (mTOR), MET, poly (ADP-ribose) polymerase (PARP) and claudin 18.2 (CLDN18.2). Trastuzumab, an anti-Her2 antibody, was approved by the U.S. FDA in 2010 as first-line therapy in combination with chemotherapy for Her2-positive disease. Since then, strategies targeting Her2 that have been successful in Her2-positive breast cancer, have failed in EGC. The one remaining study, the phase III Jacob study with pertuzumab, has yet to be presented. The anti-VEGF receptor 2 antibody, ramucirumab has been investigated as second-line therapy in 2 phase III trials, which resulted in improved survival, with subsequent FDA approval of ramucirumab in the second-line setting. Therapies targeting EGFR have been evaluated in a number of phase III studies, all of which have been negative. Phase III investigation of an mTOR inhibitor did not improve survival, although biomarker studies are awaited which may identify subgroups of patients that may benefit from its use. The results of the trials targeting MET in EGC have been disappointing, raising doubts about the usefulness of further testing agents that inhibit the MET pathway. PARP inhibition with olaparib, warrants further investigation, possibly in combination with other targeted therapies or immune checkpoint inhibition and in a biomarker-selected population. The identification of CLDN18.2 and its targeting with claudiximab is very promising and will be further investigated in a phase III study.
Background: Ipilimumab has been shown to improve overall survival in patients with metastatic melanoma; however, complete responses (CRs) are uncommon. Immune-related side effects usually involve the skin or gastrointestinal tract. Neurologic events occur less frequently but are well described. Case Report: We report the case of a 58-year-old man with metastatic melanoma who commenced ipilimumab post spinal decompression and radiation. He developed a colitis post cycle 2 and ipilimumab was discontinued. Imaging, however, documented a radiological CR. 8 weeks later, he developed paraplegia and a myelitis despite an ongoing radiological CR. Steroid use resulted in some improvement radiologically, without clinical improvement. Conclusion: We report myelitis with consequent paraplegia as a potential neurological immune-related side effect of ipilimumab. We further describe a patient with a CR after 2 cycles of ipilimumab in the setting of radiation.
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