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Purpose Uterine serous carcinoma (USC) exhibits worse survival rates compared to the endometrioid subtype, and there is currently no effective treatment options for recurrence of this disease after platinum-based chemotherapy. Activation of PIK3CA/AKT/mTOR signaling pathway is a common biological feature in USC. Materials and Methods Ipatasertib (IPAT) is an investigational, orally administered, ATP-competitive, highly selective inhibitor of pan AKT that has demonstrated anti-proliferative activity in a variety of tumor cells and tumor models. In this study, we used IPAT, carboplatin and their combination to investigate the anti-tumor activity in SPEC-2 and ARK-1 cells. Results Our results indicate that IPAT combined with carboplatin at low doses was more effective at reducing proliferation, inducing apoptosis and causing cellular stress than IPAT or carboplatin alone. In particular, inhibition of the PIK3CA/AKT/mTOR pathway and induction of DNA damage were involved in the synergistic inhibition by combination treatment of cell viability in USC cells treated with the combination. Furthermore, IPAT in combination with carboplatin significantly reduced cell adhesion and inhibited cell invasion. Conclusions These findings suggest that the combination of IPAT and carboplatin has potential clinical implications for developing new USC treatment strategies.

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e17030 Background: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. This relationship has recently been demonstrated in women with metastatic breast cancer, but there is a paucity of data regarding this correlation in women with EOC. Thus, our goal was to evaluate if sarcopenia, as assessed by computed tomography (CT) morphometric measurements, was associated with worse survival outcomes in EOC patients undergoing primary platinum and taxane-based chemotherapy. Methods: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic – version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI = SMA/height2) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and descriptive statistics was utilized to describe characteristics between the two groups. Results: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. Seventy-six percent of patients were diagnosed with Stage III or IV disease, with high-grade serous as the most common histology (74%). Median age at diagnosis was 61 years. Approximately one third were obese. Body mass index was greater in the SMI > 41 group compared to the SMI ≤ 41 group (31.3 vs 26.3, p < 0.001). There was no difference in the prevalence of chronic conditions, including diabetes, coronary artery disease, hypertension, chronic kidney disease, or tobacco use, between the two groups. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). Conclusions: Based on this patient cohort, sarcopenia was not associated with worse survival outcomes in EOC patients receiving first-line platinum and taxane-based chemotherapy. Further prospective studies are needed to explore other diagnostics that may allow us to provide improved accuracy and individualization in the care of women with advanced ovarian cancer.

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