Abstract
Background: The results from Gynecologic Oncology Group protocol 240, that blockade and non-platinum chemotherapy, predictive biomarkers are requichemotherapy plus bevacizumab significantly improves overall survival over chemotherapy alone among women with advanced cervical cancer, represents a proof of concept of the potential for anti-angiogenesis therapy and the value of systemic therapy in this disease. To identify patients likely to derive the greatest benefit from angiogenesis red and predicated on theranostics, the emerging field through which developing technologies and capabilities in the diagnostic sector can be applied to pharmacogenomics and personalized medicine. Methods: We interrogated a database of theranostic biomarkers from the CARIS repository. 592 specimens in the cervical cancer library were evaluated by a combination of sequencing (NGS), gene amplification (ISH), and protein expression (IHC). Results: NGS sequencing in 224 specimens identified mutational hotspots corresponding to PI3KCA (26%), BRCA2 (21%), BRCA1 (10%), KRAS (10%), TP53 (10%), and FBXW7 (10%). Gene amplification of EGFR (11%, 20/174) and HER2 (8%, 32/395) was also observed. IHC studies were noteworthy for the following protein signatures: anti-programmed death receptor 1 (PD1) tumor infiltrating lymphocytes (65%, 53/82); over-expression of cMET (22%, 82/376); overexpression of estrogen receptor (20%, 118/590), progesterone receptor (8%, 48/589), and androgen receptor (4%, 22/578); gemcitabine-specific low RRM1 (44%, 256/538), topotecan-specific high TOPO1 (56%, 294/528), paclitaxelrelated high TLE3 (27%, 256/537) and low TUBB3 (74%, 202/273), and pemetrexed-related low TS (48%, 256/537). Conclusion: The August 14, 2014 U.S. FDA approval of bevacizumab for advanced cervical cancer constitutes a regulatory milestone that fulfills a high unmet clinical need. Our data support the inclusion of theranostic biomarkers to help guide therapy in clinical trials for patients who have progressed on antiangiogenesis therapy or who are considered otherwise incurable. Poly-ADPribose polymerase inhibition, MEK, cell cycle checkpoint, and PI3K/AKT/mTOR pathway inhibitors, EGFRand HER2-directed therapy, immunotherapy, hormonal therapy, and non-platinum chemotherapy may be suitable for study. Abstract (#3911)
Published Version
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