Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial.

5514 Background: In the Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644), the addition of maintenance olaparib to bev in pts with newly diagnosed advanced high-grade ovarian cancer (HGOC) resulted in a significant PFS benefit, particularly in HRD-positive (HRD+) pts (hazard ratio [HR] 0.33; 95% CI 0.25–0.45) (Ray-Coquard et al. NEJM 2019). We explored efficacy in HRD+ pts by disease stage. Methods: Pts with newly diagnosed, FIGO stage III–IV HGOC in response after platinum-based chemotherapy + bev received bev (15 mg/kg q3w for 15 months [mo]) + either olaparib (300 mg bid for 24 mo) or placebo (pbo). This exploratory analysis evaluated PFS (data cut-off [DCO]: Mar 22 2019) and PFS2 (DCO: Mar 22 2020) in HRD+ pts (tumor BRCA1/ BRCA2 mutation [tBRCAm] or genomic instability score [Myriad myChoice HRD Plus] ≥42) by FIGO stage. Results: 387/806 randomized pts (48%) were HRD+; 272/387 (70%) had stage III disease and 115/387 (30%) had stage IV disease. 153 (56%) HRD+ stage III pts and 61 (53%) HRD+ stage IV pts had a tBRCAm. Among HRD+ stage III pts, 172 (63%) had upfront surgery (51/172 [30%] had residual disease) and 90 (33%) had interval surgery (19/90 [21%] had residual disease); 52 (45%) HRD+ stage IV pts had upfront surgery (34/52 [65%] had residual disease) and 55 (48%) had interval surgery (18/55 [33%] had residual disease). Median follow-up for PFS and PFS2 was respectively 24.8 and 37.2 mo in HRD+ stage III pts and 24.0 and 37.0 mo in HRD+ stage IV pts. Median PFS, PFS2 and HRs are in the Table. Among HRD+ stage III pts, 36-mo PFS2 (olaparib + bev vs pbo + bev) was 74% vs 60%; among HRD+ stage IV pts, 53% vs 30%. Among HRD+ stage III pts with no residual disease after upfront surgery, HR (95% CI) for PFS was 0.15 (0.07–0.30) and for PFS2 was 0.22 (0.06–0.67). Among HRD+ stage III pts with residual disease after upfront surgery or who received neoadjuvant chemotherapy, or HRD+ stage IV pts, HR (95% CI) for PFS was 0.38 (0.27–0.53) and PFS2 was 0.68 (0.46–1.03). Conclusions: In the PAOLA-1 study, maintenance olaparib + bev provided a PFS and PFS2 benefit over pbo + bev in HRD+ pts, irrespective of FIGO stage and residual disease after upfront surgery. Clinical trial information: NCT02477644. [Table: see text]

Impact on survival of surgical therapeutic strategy in the initial management of advanced ovarian cancer: A study from the Cote d’Or gynaecological cancer registry from 1998 to 2015.

e17537 Background: The management of ovarian cancer is based on a combination of surgery and chemotherapy. The aim of surgery is to achieve zero residual tumour at the end of the procedure. In advanced stage ovarian cancer, two therapeutic approaches are possible: primary debulking surgery, or primary chemotherapy followed by interval debulking surgery. The primary objective of this study was to describe overall survival (OS) in FIGO stage III and IV ovarian cancers according to the therapeutic sequence (i.e. primary surgery or interval surgery). Methods: We performed a retrospective, observational study using data from the gynecological cancer registry of the Cote d’Or, for patients diagnosed with FIGO stage III or IV ovarian cancer between 1998 and 2015. We recorded FIGO stage, histological type, treatment and completeness of cytoreduction. Results: In total, 460 patients were included. OS at 5 years was 47% in patients with primary surgery, versus 38% in patients with interval surgery (p = 0.06). Five-year OS was 45% in patients with complete cytoreduction, versus 30% in those with incomplete cytoreduction (p < 0.001). The rate of complete cytoreduction was 43% in patients with primary surgery, versus 55% in those with interval surgery. Conclusions: OS appears to be slightly better in patients receiving primary surgery, and when cytoreduction is complete. Every effort should be made during surgery to achieve complete cytoreduction, by an experienced team. Primary surgery should be preferred in these patients.

Feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer during COVID-19 pandemic

ObjectiveThis study aims to evaluate the effect of the COVID-19 pandemic and related restrictions on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer.MethodsWe retrospectively evaluated ovarian cancer patients who underwent HIPEC following complete cytoreductive surgery performed during the outbreak of the COVID-19 pandemic in three different centers specializing in gynecological oncology. All patients who underwent cytoreduction plus HIPEC for a primary, interval, and recurrent surgery were evaluated. Primary outcomes was postoperative 30-day morbidity and mortality. The secondary outcome was infection of patient and/or related staff with COVID-19 during the perioperative or early postoperative period.ResultsWe performed a total of 35 HIPEC procedures during the pandemic: 15 (42.9%) patients underwent primary/interval surgery, while 20 (57.1%) patients had recurrent disease. Grade 3–4 complications occurred in one patient (2.9%) (chronic renal failure), while mortality did not occur in any patient. Neither the patients nor related staff were infected with the coronavirus during the perioperative or early postoperative period. One patient, who was diagnosed with COVID-19 pneumonia on postoperative day 80 died from the infection. Another patient died on postoperative day 85 due to progressive ovarian cancer, a disorder in vital functions, and organ failure.ConclusionHIPEC during the COVID-19 pandemic seems a safe and feasible procedure, with acceptable morbidity and mortality rates. Careful selection of patients is important and precautions should be taken before the procedure.

Pathologic distribution at the time of interval tumor reductive surgery informs personalized surgery for high-grade ovarian cancer

IntroductionThe surgical approach for interval debulking surgery after neoadjuvant chemotherapy has been extrapolated from primary tumor reductive surgery for high-grade ovarian cancer. The study objective was to compare pathologic distribution of malignancy at interval debulking surgery versus primary tumor reductive surgery.MethodsPatients with a diagnosis of high-grade serous or mixed, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer who underwent neoadjuvant chemotherapy or primary tumor reductive surgery and had at least 6 months of follow-up were identified through tumor registry at a single institution from January 1995 to April 2016. Pathologic involvement of organs was categorized as macroscopic, microscopic, or no tumor. Statistical analyses included Mann-Whitney and Fisher’s exact tests.ResultsOf 918 patients identified, 366 (39.9%) patients underwent interval debulking surgery and 552 (60.1%) patients underwent primary tumor reductive surgery. Median age was 62.3 years (range 25.3–92.5). The majority of patients in the interval debulking surgery group were unstaged (261, 71.5%). In the patients who had a primary tumor reductive surgery, 406 (74.6%) had stage III disease. In both groups, the majority of patients had serous histology: 325 (90%) and 435 (78.8%) in the interval debulking and primary tumor reductive surgery groups, respectively. There was a statistically significant difference between disease distribution on the uterus between the groups; 31.4% of the patients undergoing interval debulking surgery had no evidence of uterine disease compared with 22.1% of primary tumor reductive surgery specimens (p<0.001). In the adnexa, there was macroscopic disease present in 253 (69.2%) and 482 (87.4%) of cases in the interval vs primary surgery groups, respectively (p<0.001). Within the omentum, no tumor was present in the omentum in 52 (14.2%) in the interval surgery group versus 91 (16.5%) in the primary surgery group (p<0.001). In the interval surgery group, there was no tumor involving the small and large bowel in 49 (13.4%) and 28 (7.7%) pathologic specimens, respectively. This was statistically significantly different from the small and large bowel in the primary surgery group, of which there was no tumor in 20 (3.6%, p<0.001) and 16 (2.9%, p<0.001) of cases, respectively.ConclusionIn patients undergoing interval debulking surgery, there was less macroscopic involvement of tumor in the uterus, adnexa and bowel compared with patients undergoing primary cytoreductive surgery.

Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

PURPOSE In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed BRCA1- and/or BRCA2-mutated advanced ovarian cancer compared with placebo (hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41; median not reached v 13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors. PATIENTS AND METHODS Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete [CR] or partial response [PR]), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status ( BRCA1 or BRCA2). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate. RESULTS The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a BRCA1 or BRCA2 mutation, respectively. CONCLUSION Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.

Series of 55 pregnancies following ulipristal acetate treatment of symptomatic uterine fibroids

Introduction: Treatment with ulipristal acetate effectively controls excessive bleeding due to uterine fibroids and reduces their size. Uterine fibroid size reduction is expected to improve the results of the myomectomy and the reproductive prospects of the patient. Methods: Retrospective and descriptive analysis of a series of 53 patients who achieved pregnancy after being treated for symptomatic uterine fibroids. The primary endpoints were pregnancy and birth outcomes in women with symptomatic uterine fibroids that conceived following at least one course of therapy with ulipristal acetate 5 mg/day. The secondary endpoints were time until pregnancy, reasons for ulipristal acetate treatment, number of treatment courses completed, hemorrhagic control achievement, hemoglobin levels, fibroid FIGO classification, largest fibroid diameter, and type of myomectomy (if any). Results: Fifty-five pregnancies were registered in 53 patients following ulipristal acetate therapy (43 live births, 9 miscarriages, and 3 ongoing pregnancies). Half of the patients became pregnant without interval surgery. Bleeding control was achieved in 96% of the cases. A significant increase (p < 0.001) in hemoglobin levels and a reduction (p < 0.001) in uterine fibroid size was observed after treatment. No malformations were reported among newborns after ulipristal acetate therapy. Conclusion: So far, this is the largest case series reporting both pregnancy and birth outcomes following ulipristal acetate therapy for uterine fibroids. Our data support favorable outcomes after therapy for this population subset.

P085 DOSE ESCALATION (Q4) OF USTEKINUMAB SHOULD BE CONSIDERED FOR CROHN’S DISEASE PATIENTS WHO FAIL STANDARD DOSING

Background Ustekinumab, a monoclonal antibody of interleukin-12 and interleukin-23, was approved for the treatment of moderate to severe Crohn’s disease (CD) in 2016. Ustekinumab is approved in CD for a weight-based IV induction dose followed by every 8 weeks of subcutaneous dosing. Response rates by 6 weeks range from 34% (anti-TNF failures) to 56% in bio-naïve patients. The remainder includes patients who partially-respond (PR) or do not respond (NR). Response by week 16 is 55% (anti-TNF failures) and 73% in bio-naïve patients suggestive of a ‘delayed response’ in some. Experience with anti-TNF drugs demonstrates that a subset of patients respond to dose escalation, which prompts the notion of a potential delayed response phenomenon with Ustekinumab. Aim Determine the efficacy of dose escalation from standard Q8 dosing to Q4 dosing of Ustekinumab in CD patients, who had PR or NR to standard Q8 dosing. Methods A Retrospective observation study of 143 adult patients with CD, on Ustekinumab standard Q8 dosing over a 2 year and 9-month period was conducted. Data was extracted pertaining to demographics, disease, and treatment-related variables (biomarkers, steroid use, interval surgery, ER visits). Patients were further subcategorized as responders, partial responders(PR), and non-responders(NR), based on changes in fecal calprotectin, albumin, CRP, and Physician Global Assessment Disease Severity (1=mild, 2=moderate, 3=severe). Q8 non-responders (NR) and partial responders (PR) were dose-escalated to Q4, and outcome variables were collected. Biomarkers, steroid utilization, interval surgery, and ER visits, and PGA were compared in Q8 partial responder(PR) and non-responders (NR) from the date of starting Ustekinmuab on Q8 dosing to the date of escalation to Q4 dosing, versus the date of escalation Q4 dosing to the end of patient follow up. Results 30% (n=8) of patients were Q8NR, and 70% (n=19) were Q8PR). In the PR group, biomarkers decreased by up to 21% when these patients were switched to Q4 dosing. 100% of patients saw clinical improvement or remained at mild disease on Q4 dosing. In the NR group, biomarkers decreased by up to 91%. 100% of patients saw clinical improvement or remained at mild disease while on Q4 dosing. In both groups, 50% of patients taking steroids on Q8 dosing were no longer taking steroids or were at a reduced dose at the end of Q4 dosing follow-up. 40% of patients on immunomodulators on Q8 dosing were no longer taking immunomodulators at the end of Q4 dosing follow-up. Conclusions