Treatment options for advanced cervical cancer are limited and patients experiencing recurrence after first-line cisplatin-based chemotherapy and bevacizumab have a poor prognosis. A recent phase II study in advanced cervical cancer has demonstrated a disease control rate of 68.4% with the immune checkpoint inhibitor nivolumab. By blocking immune checkpoints, immunotherapy puts the immune system into a state of hyper-activation that can cause immune-related adverse events. We present the clinical, pathological and molecular data of a patient with metastatic cervical cancer and progressive disease after second-line therapy. We report on the therapeutic response under third-line immunotherapy with nivolumab, the immune-related adverse events (IRAE), and their successful management. We report the case of a 62-year-old woman who was diagnosed with advanced squamous cell carcinoma of the cervix with paraaortic lymph node metastases. After an initial combined radio-chemotherapy with cisplatin, she developed local and nodal (supraclavicular) recurrence. Second-line chemotherapy with 6 cycles of carboplatin, paclitaxel, and bevacizumab resulted in a partial response for 6 months. Checkpoint inhibition with nivolumab was started due to progression, leading to persistent complete remission. Immunotherapy was well tolerated for 8 months until the patient presented with an immune-related isolated vulvitis, which was successfully managed with topical corticosteroids. The persistent complete response after third-line treatment for relapsed chemotherapy-resistant cervical cancer presented in this case highlights the potential of immunotherapy for patients with advanced cervical cancer impressively. To our knowledge, this is the first report of an isolated immune-related vulvitis under nivolumab. This adverse event might be underdiagnosed and mistreated, however, it is of importance due to its impact on quality of life, sexual wellbeing and compliance of patients. Successful IRAE management may enable prolonged immune checkpoint inhibitor therapy. In the future, routine molecular tumour profiling is likely to aid in the stratification of cervical cancer patients for immunotherapy. Here, we provide the methylome data of a case with complete response.

Endocrine therapy is an effective treatment for low-grade serous ovarian cancer. However, the role of estrogen and progesterone receptors as biomarkers for high-grade serous ovarian cancer (HGSOC) is yet to be elucidated because not all estrogen and progesterone receptor-positive tumors benefit from anti-estrogen therapy. The degree of expression is presumed to play a vital role; however, that role is not well-defined in ovarian cancer. We aimed to determine the role of estrogen and progesterone receptor expression in primary and paired relapsed HGSOC. In this study, primary and matched relapsed tumor samples were collected from 80 patients with International Federation of Gynecology and Obstetrics Stage II–IV HGSOC. Tissue microarray was conducted and immunohistochemistry for estrogen and progesterone receptor expression was performed. Two independent pathologists performed the tissue microarray analysis with the Immunoreactive Score and Allred Total score. In the paired analysis, no significant difference in estrogen receptor expression was observed. However, progesterone receptor expression was significantly lower in patients with recurrent platinum-sensitive HGSOC. We conclude that anti-estrogen therapy targeting estrogen receptor positive HGSOC could be administered in primary and relapsed settings. The use of endocrine maintenance with an aromatase inhibitor in patients with estrogen receptor positive HGSOC needs to be further evaluated and validated in a randomized controlled trial.

Purpose: The stage of disease is one of the strongest prognostic factors in epithelial ovarian cancer. The International Federation of Gynecology and Obstetrics (FIGO) classification was revised in 2013; stage IC was subdivided into IC1 (intraoperative surgical spill), IC2 (capsule rupture before surgery or tumor on surface), and IC3 (positive peritoneal washing or ascites). Our aim was to compare the outcome of patients in the new FIGO stage I subgroups, as this might influence adjuvant therapy decisions. Patients and methods: Patient databases of three gynecological oncology centers were retrospectively analyzed. Patients with FIGO stage I ovarian cancers were restaged according to the revised classification, based on operative and pathological reports, and determined patient outcomes. Results: We analyzed 128 patients with ovarian cancers. In FIGO IA, we found 11.3% recurrences and 4.2% deaths. In FIGO IC, 21.8% of the patients recurred and 7.3% died. There was a trend toward a shorter time to recurrence when comparing IA to IC (P=0.076). Within all new subgroups of FIGO IC, there was no difference in time to recurrence (P=0.59). There was also no significant difference in survival when FIGO IA was compared to FIGO IC in comparison with the new individual classifications (IA to IC, IA to IC1, 2, or 3; P=0.60, P=0.15, P=0.61, P=0.66, respectively) or within the different subgroups (P=0.56). Platinum-based chemotherapy was given to the majority (82.6%, n=38/46) of the FIGO IC patients compared to 30.9% in FIGO IA (n=17/55). There was no significant difference within the new subgroups of FIGO IC (P=0.88). Conclusion: In our retrospective analysis, the new FIGO staging of IC ovarian cancers did not predict prognosis, but the use of adjuvant chemotherapy in 82.6% of the stage IC patients may have biased the outcome.

Background: Exposure to paclitaxel and carboplatin has the risk of developing hypersensitivity reactions (HSRs), which could necessitate using less effective treatments to avoid anaphylaxis. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen; therefore, this study investigated rates and benefits of successful desensitization in patients with gynecologic cancers (GC).Methods: We collected data from 241 patients with GC who had at least one cycle of platinum or taxane chemotherapy. The rate of HSRs and successful desensitization were evaluated, and an outcome analysis was conducted.Results: The rate of HSRs to platinum and taxane was 6.39% and 13.07%, respectively. We observed a 100% success rate of desensitization in our cohort. Patients with HSR were significantly younger (57.1 vs. 64.9 years, p = 0.030) in the taxane cohort. Importantly, the overall survival (OS) of patients with platinum and taxane HSRs who underwent desensitization was comparable to that of patients with no HSRs (platinum vs. controls; median OS 60.36 vs. 60.39 months, p = 0.31; taxane vs. controls; OS 80.29 vs. 60.00 months, p = 0.59).Conclusion: Thus, we show that desensitization for platinum and taxane HSRs is safe and effective, resulting in an outcome that is well comparable to patients without HSR. Based on these observations, desensitization procedures might be considered as standard of care before switching to less effective treatment for patients with GC.

5515 Background: Ovarian cancer (OC) is mostly diagnosed as G3 serous advanced stage disease with survival of only 20% in 5 years. Maintenance therapy after 1st line chemotherapy is increasingly used, particularly with Bevacizumab or PARP inhibitors. However, the effect of antihormonal treatment in breast cancer but also in relapsed gynecological cancers has been shown. Also in low grade OC, data are highly supportive of antihormonal treatment. In a previous study of ours, also high grade serous cancers express high amounts of estrogen receptor (ER). The aim of this study was to analyze whether a maintenance antihormonal therapy in advanced OC adds a benefit in relation to the time of recurrence. Methods: All newly diagnosed G3 FIGO III/IV OC cases at our Hospital were assessed prospectively for ER expression. Patients with positive ER status (> 10%) were treated as maintenance therapy with Letrozol 2.5mg 1x/d or not. Progression free survival was recorded and analyzed according to Kaplan-Meier. Patients with macroscopic residual disease post surgery receiving Bevacizumab maintenance treatment were also included. Results: We identified 51 patients with G3 serous OC FIGO III/IV expressing ER. Hereby, 24 patients received and 27 patients did not receive Letrozol after adjuvant chemotherapy. Time to progression ranged from 4 to 121 months. The use of Letrozol was associated with a significant prolonged progression free interval. After 12 months, only 65% of women in the control group vs 84% in the Letrozol group were progression-free. After 24 months, the effect was even stronger (46% in the control group vs 74% with Letrozol (p= 0.02)). Within the subgroup of patients with residual disease treated with Bevacizumab a similar effect was seen with 41% of patients progression free after 12 months vs 89% when taking Letrozol in addition to Bevacizumab. Conclusions: The use of Letrozol as a maintenance therapy after the 1st line treatment in G3 advanced stage serous OC patients was associated with a longer recurrence free interval in our cohort. These findings warrant a randomized controlled trial comparing all existing maintenance regimen as this might have a major influence on cost development in OC treatment.