P86.07 CDK12 Mutated Extensive Stage Small Cell Lung Cancer Showed an Exceptional Response to Olaparib and Paclitaxel

The poly ADP ribose polymerase (PARP) expression is significantly higher in SCLC than normal lung epithelial cells and other histologic subtypes of cancer. In preclinical models, the loss function mutation Cyclin-dependent kinase 12 (CDK12) was related to PARP inhibitor sensitivity (Bajrami et al., 2014). This found 1.7% (Julie 2015). However, little known about clinical implications CDK12 mutated small cell We present a 71-year old male with extensive stage cancer harboring splice site single nucleotide variation (SNV) mutation. PET scan CT showed metastases bone, liver, brain. His disease progressed no response carboplatin/etoposide/atezolizumab combination therapy, irinotecan, ipilimumab/nivolumab therapy. Circulating tumor DNA Next Generation Sequencing (NGS) assay (Guardant360) revealed CDK12, PIK3CA, BRAF, TP53 M246V CCNE1 Tissue NGS (TEMPUS) confirmed TP53, RB1, MYCL, ATP7B He given olaparib, inhibitor, combined paclitaxel based on his mutation, which sensitize inhibitors. Olaparib 300mg twice day, 150mg/m2 every three weeks schedule. A 6-week follow-up abdomen marked shrinkage metastatic lesions liver as seen Fig. 1 (1a: pre-treatment, 1b: scans). 40% decrease sum length diameters consistent partial per RECIST 1.1 criteria. observed deep durable ongoing for more five months this patient receiving olaparib/paclitaxel dose reduced 80mg/m2 due worsening neuropathy bilateral lower extremities. Fig.1 case illustrates need further exploration taxanes therapy treatment especially It remains unclear how associated sensitization Further trials are required or solid tumors