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Highlights • The COVID-19 pandemic has required adaptability in the workplace. • Women health care professionals are disproportionately affected by the burdens resulting from the pandemic. • Flexible work options are critical to ensure staff have the resources to provide cancer care and clinical trial options., Despite the impact of the COVD-19 pandemic and public health crisis on health care delivery, the GOG-Foundation has continued to prioritize the delivery of novel and state-of-the-science treatment options to patients via clinical trials.

The role of retroperitoneal lymph node dissection (RPLND) in testicular cancer is well established in both the primary and post-chemotherapy setting. The aim of this study was to report our 2 years oncological outcomes of robotic RPLND. A retrospective review was performed of all patients undergoing robotic RPLND by a single surgeon at Princess Margaret Cancer Centre. Demographic, perioperative, and oncologic data were analyzed using descriptive statistics. Between September 2014 and June 2020, 141 patients underwent an RPLND [33 (23.4%) were primary, 108 (76.6%) were post-chemotherapy]. 27 (19.1%) patients underwent a robotic bilateral template nerve-sparing RPLND. RPLND indication was primary (i.e. pre-chemotherapy) in 18 (66.7%), and post-chemotherapy in 9 (33.3%) patients. Stage at RPLND was 2A (n = 15, 55.6%), 2B (n = 9, 33.3%), 2C (n = 1, 3.7%) and 3 (n = 2, 7.4%). Median OR time (incision to closure) was 525 min and blood loss was 200 ml. Nerve sparing was performed in all but one case. Six (22.2%) adjuvant procedures were performed including two (7.4%) vascular repairs. Median length of stay was 2 days. Viable tumor was detected in 17 (63%) and teratoma in 9 (33.3%). Median follow-up was 31.3 months. No adjuvant chemotherapy was given. Three patients (11.1%) relapsed: 2 out-of-field and 1 with both in-field and out-of-field disease. Robotic RPLND can be performed safely. Long-term follow-up of series such as ours, enriched with patients with viable disease and/or teratoma, and not treated with adjuvant chemotherapy is required to ensure oncological outcomes are comparable to the open approach.

LBA5500 Background: While PARP inhibitors have shown efficacy as first-line (1L) maintenance treatment for patients (pts) with ovarian cancer (OC), questions remain about the pt population that may benefit from their use. ATHENA (NCT03522246) was designed to test if rucaparib may be effective as 1L maintenance treatment in a broad pt population, including those without BRCA mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. Here we report results from the ATHENA–MONO comparison of rucaparib vs placebo. Methods: Pts with stage III–IV high-grade OC who had completed cytoreductive surgery (R0 permitted) and 4–8 cycles of 1L platinum-doublet (bevacizumab allowed with chemotherapy) with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Pts were stratified by HRD status (as determined by FoundationOne CDx), residual disease status after chemotherapy, and timing of surgery. The primary endpoint of investigator-assessed PFS per RECIST was assessed in a step-down procedure first in the HRD population (BRCA mutant or BRCA wild-type/loss of heterozygosity [LOH] high carcinoma) and then in the intent-to-treat (ITT) population. Blinded independent central review (BICR)–assessed PFS was a stand-alone, secondary endpoint. PFS in BRCA mutant and HRD-negative pts (BRCA wild-type/LOH low) were exploratory endpoints. Results: As of Mar 23, 2022 (visit cutoff), 427 and 111 pts were randomized to rucaparib monotherapy or placebo (median time on treatment, 14.7 and 9.9 mo). PFS data are shown in the Table. Most common grade ≥3 TEAEs were anemia (rucaparib, 28.7% vs placebo, 0%), neutropenia (14.6% vs 0.9%), and ALT/AST increased (10.6% vs 0.9%). Rucaparib dose reduction, interruption, and discontinuation due to TEAEs occurred in 49.4%, 60.7%, and 11.8% of pts. Conclusions: Rucaparib monotherapy is effective as 1L maintenance with significant benefit vs placebo observed in the ITT and HRD populations, as well as the non-nested subgroup of pts without known HRD. Clinical trial information: NCT03522246. [Table: see text]

TPS5609 Background: ARTISTRY-7 will evaluate the novel engineered cytokine nemvaleukin alfa (nemvaleukin, ALKS 4230) in pts with gynecologic cancers. Epithelial ovarian cancer (OC) is the 7th most common cause of cancer mortality in women. OC is an area of high unmet need, as many pts become resistant or refractory to frontline platinum-based chemotherapy. Nemvaleukin was designed to selectively bind to the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating and expanding antitumor CD8+ T and NK cells with minimal expansion of Tregs. This selectivity may provide enhanced tumor killing and improved safety/tolerability compared with high-dose IL-2. In clinical studies, nemvaleukin, as monotherapy and in combination with pembrolizumab, has shown evidence of clinical benefit in multiple tumor types, including OC. In ARTISTRY-1, 4 responses were observed in pts with OC, including 2 complete responses, 1 in a pt with platinum-resistant OC and 5 prior lines of therapy, and 2 partial responses. Methods: ARTISTRY-7 is a phase 3, multicenter, open-label randomized study of nemvaleukin and/or pembrolizumab vs chemotherapy. Eligible pts are women (≥18 y) with histologically confirmed epithelial OC (high-grade serous, endometrioid, clear cell), fallopian tube cancer, or primary peritoneal cancer. Pts must have received ≥1 prior line of systemic therapy in the platinum-sensitive setting, ≤5 prior lines in the platinum-resistant setting, and prior bevacizumab, with radiographic progression on most recent therapy. Primary platinum-refractory disease (progression on first-line platinum therapy) or primary platinum resistance (progression < 3 months after completion of first-line platinum therapy) is exclusionary. Pts must have ECOG performance status of 0 or 1, estimated life expectancy of ≥3 months, and adequate hematologic reserve and hepatic and renal function. Approximately 376 pts will be randomized (3:1:1:3) to receive nemvaleukin 6 μg/kg IV on days 1-5 and pembrolizumab 200 mg IV on day 1 of each 21-day cycle, pembrolizumab monotherapy, nemvaleukin monotherapy, or chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan, or gemcitabine) and stratified according to PD-L1 status, histologic subtype (high-grade vs non–high-grade serous), and chemotherapy (paclitaxel vs other). Pts will continue treatment until disease progression or intolerable toxicity (maximum 35 cycles for pembrolizumab; nemvaleukin can be continued). The primary endpoint is investigator-assessed PFS (RECIST v1.1) in the nemvaleukin/pembrolizumab vs chemotherapy group. Secondary/exploratory endpoints include overall survival, other antitumor measures, safety, health-related quality of life, and pharmacokinetic/pharmacodynamic effects. Clinical trial information: NCT05092360.

BACKGROUND: Little is known regarding what sociodemographic characteristics and reasons for use are associated with adolescent solitary alcohol and marijuana use. METHODS: Data from 7,845 12(th) grade students participating in the nationally-representative Monitoring the Future study from 2015-2021 were used to examine cross-sectional associations between sociodemographics, heavy drinking/marijuana use, reasons for use, and past 12-month solitary alcohol or marijuana use among past 12-month users. Historical trends and possible differences related to the COVID-19 pandemic also were examined. RESULTS: Solitary use prevalence increased from 2015 to 2021 with no evidence of significant COVID-19 deviations. In 2021, solitary alcohol use was reported by 32.1% (SE 3.01) and solitary marijuana use by 55.8% (4.72) of those reporting past 12-month use. Common and substance-specific sociodemographic risk factors were observed. Binge drinking was associated with solitary alcohol use; frequent marijuana use was associated with solitary marijuana use. Reasons for use related to coping with negative affect were associated with solitary use. Compulsive use reasons were more strongly associated with solitary alcohol than marijuana use. Drinking to have a good time with friends was negatively associated with solitary alcohol use but this association was not seen for solitary marijuana use. CONCLUSIONS: The percentage of adolescents who use alcohol or marijuana when they were alone has increased among those who report using each substance. Associations between solitary use and (a) higher levels of consumption and (b) coping with negative affect highlight the importance of solitary use as a risk indicator.

5544 Background: In ARIEL3 (NCT01968213), rucaparib maintenance treatment led to significant improvement vs placebo for the primary endpoint of investigator-assessed progression-free survival (PFS) in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma responsive to the last line of platinum therapy (Coleman et al. Lancet. 2017;390:1949–61). The largest benefit was observed in pts with carcinomas with a BRCA mutation or high loss of heterozygosity (LOH), a marker of homologous recombination deficiency (HRD). However, rucaparib also improved PFS in pts with carcinomas negative by HRD test (ie, BRCA wild-type with low LOH), a subset of pts for which there is no identified molecular mechanism conferring PARP inhibitor sensitivity. Among these pts (rucaparib, n = 107; placebo, n = 54), median PFS was 6.7 vs 5.4 months, respectively (HR, 0.58 [95% CI 0.40–0.85]; P= 0.0049), and 31.8% vs 4.3% were progression-free at 1 yr. In this post hoc exploratory analysis, we further evaluated the efficacy of rucaparib maintenance vs placebo in this subset of pts. Methods: Pts were randomized 2:1 to oral rucaparib (600 mg BID) or placebo. For this analysis, investigator-assessed PFS and safety were evaluated in pts with HRD-negative carcinoma, defined as BRCA wild-type with genomic LOH < 16% using Foundation Medicine’s T5 NGS assay. Results: Visit cutoff dates for efficacy and safety were Apr 15, 2017, and Dec 31, 2019. Across subgroups based on demographic or disease characteristics, the trend of rucaparib benefit vs placebo was consistently observed in pts with HRD-negative carcinoma (Table). The safety profile of rucaparib in the HRD-negative population was consistent with that of the overall safety population reported previously. Conclusions: Rucaparib maintenance reduced risk of progression in pts with ovarian carcinomas, including those not associated with HRD, regardless of clinical prognostic factors. [Table: see text]

TPS5620 Background: Chemotherapy resistance is a major concern in the treatment of advanced platinum-resistant and platinum-refractory ovarian cancer. One mechanism of resistance is driven by cortisol, which can suppress the apoptotic pathways that chemotherapy agents rely upon, eg, suppression of BCL2 and FOXO3a pathways. Preclinical and clinical data indicate that glucocorticoid receptor (GR) antagonism may reverse the anti-apoptotic effects of cortisol, thereby restoring the efficacy of cytotoxic agents. Relacorilant is a selective GR modulator that has shown promise in overcoming resistance when combined with taxanes (particularly nab-paclitaxel) in preclinical models (Greenstein & Hunt 2021) and early-phase clinical studies (Munster et al. 2019) in various solid tumors. A randomized, controlled phase 2 study of relacorilant + nab-paclitaxel found clinically meaningful improvements in progression-free survival (PFS) and duration of response (DOR) without increased side effect burden in patients with recurrent, platinum-refractory and platinum-resistant ovarian cancer (Colombo et al. 2021). The aim of this phase 3 study is to confirm these phase 2 findings in a larger patient population. Methods: ROSELLA (EudraCT 2022-000662-18, NCT pending) is a phase 3, randomized, 2-arm, open-label, multicenter study of relacorilant + nab-paclitaxel compared to investigator’s choice of chemotherapy agents in patients with confirmed high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. The trial is being conducted at multiple sites in North America and Europe and has a planned enrollment of 360 patients. Patients are randomized 1:1 to either relacorilant (150 mg the day before, day of, and day after nab-paclitaxel infusion) + nab-paclitaxel (80 mg/m2 on days 1, 8, and 15 of each 28-day cycle) or investigator’s choice of chemotherapy (liposomal doxorubicin, paclitaxel, topotecan, or nab-paclitaxel). Randomization is stratified by prior lines of therapy (1 vs > 1), region of world (North America vs Europe), and prior bevacizumab (yes/no). Adult female patients with platinum-resistant disease (progression within 6 months of completion of platinum-containing therapy), excluding patients with primary platinum refractory disease, who have received 1–3 lines of prior systemic anticancer therapy and at least 1 prior line of platinum therapy are being enrolled. Life expectancy ≥3 months, adequate organ function, and ECOG performance status of 0 or 1 are required. The primary study endpoint is PFS by blinded independent central review. Key secondary endpoints include overall survival, PFS by investigator, overall response rate, best overall response, DOR, clinical benefit rate, safety, quality of life, CA-125, pharmacodynamics, and pharmacokinetics. Clinical trial information: 2022-000662-18.

5552 Background: Tolerability is a key consideration when selecting a PARP inhibitor (PARPi) for ovarian cancer (OC). Here we expand on earlier work (Arend et al 2021) to further characterize real-world tolerability and dose modifications in US patients (pts) with OC receiving PARPi therapy. Methods: A retrospective cohort of OC pts starting olaparib (ola), niraparib (nir) or rucaparib (ruc) between Jan 2017 and Dec 2020 was identified from MarketScan® Commercial/Medicare Supplemental databases, increasing the period covered and number of pts included vs our previous analysis. Pts were followed up from first PARPi prescription (index) for ≥30 days until end of study period, disenrollment or death; baseline was 6 months pre-index. Clinical events of interest (CEIs; acute myeloid leukemia/myelodysplastic syndromes, anemia, leukopenia/neutropenia, thrombocytopenia, acute kidney injury, arthralgia, constipation, diarrhea, nausea, vomiting, dermatitis/rash/photosensitivity, fatigue, hypertension, infection, insomnia, pneumonitis, transaminitis) were identified via ICD-9/10 codes. Multivariable Cox regression compared the likelihood of CEIs, dose modifications and hospitalizations between PARPis, adjusting for baseline CEI, Charlson Comorbidity Index score, prior bevacizumab and cancer-related surgery. Persistence was defined as no PARPi treatment gaps of >90 days in pts with ≥6 months’ continuous enrollment. Results: Overall, 637, 538 and 227 pts received ola, nir and ruc, respectively (median [IQR] follow-up 10.5 [13.4] months). Baseline characteristics were similar across groups. The proportion of pts initiating PARPi at the highest indicated dose was 89.2%, 57.6% and 89.9% for ola, nir and ruc, respectively; 22.6%, 34.8% and 28.6%, respectively, required dose decreases. The likelihood of experiencing CEIs varied across the PARPis after adjusting for a priori confounders as shown in the table. Persistence with index PARPi was higher with ola (83.4%) vs nir (73.3%; P0.05). Among all pts, mean time to non-persistence was shorter with nir vs ola and ruc (6.4 vs 7.9 and 7.6 months, respectively; both P

5574 Background: Available chemotherapies for platinum-resistant ovarian cancer (PROC) have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is a first-in-class antibody drug conjugate (ADC) comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent that has demonstrated significant anti-tumor activity in this difficult to treat population. The objective is to characterize the tolerability profile of MIRV in a pooled analysis of experience when administered as monotherapy in patients (pts) with FRα positive recurrent ovarian cancer. Methods: Retrospective pooled analysis included pts enrolled across three studies: phase 1 first-in-human, phase 3 FORWARD I, and phase 3 SORAYA. Analysis included pts with FRα positive recurrent ovarian cancer and those pts with low, medium, and high FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 25% of cells with PS2+ staining intensity). All pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. Results: 464 pts were included from 15 countries, with key characteristics: median age 63 yrs, 87% 1-3 prior therapies, 91% platinum free interval ≤6 months, 65% prior bevacizumab, and 25% prior PARPi. The most common treatment-related adverse events (TRAE) (all grade, grade 3+) included blurred vision (42%, 3%), nausea (40%, 2%), diarrhea (33%, 2%), fatigue (31%, 2%), keratopathy (26%, 3%), and dry eye (22%, 1%). TRAEs leading to a dose delay or reduction occurred in 33% and 21% of pts, respectively. Seven % discontinued due to a TRAE. Four pts ( < 1%) discontinued MIRV due to an ocular event. Ninety % of pts with a grade 2+ blurred vision resolved to grade 0 or 1, 93% of pts with grade 2+ keratopathy resolved to grade 0 or 1. No corneal ulcers or perforation have been reported and no patient with a serious ocular event has been reported to have permanent sequelae. Conclusions: In a pooled analysis of 464 patients, MIRV monotherapy has a differentiated and predictable safety profile consisting primarily of low grade and reversible gastrointestinal and ocular events. These events were managed with supportive care and dose modifications if needed, with a low rate of treatment-related discontinuation. The safety profile of MIRV in recurrent ovarian cancer along with the anti-tumor activity in PROC (32.4% ORR Matulonis SGO 2022) support a favorable benefit/risk in this population. Clinical trial information: NCT01609556, NCT04296890, NCT02631876.

TPS5619 Background: Oregovomab, a murine IgGκ1 monoclonal antibody, has high affinity binding to tumor associated antigen CA125, thus, rendering the target antigen CA125 more immunogenic or “neoantigen-like” through altered and enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when oregovomab is combined with chemotherapy. In a randomized phase II study, oregovomab in combination with paclitaxel and carboplatin (PC) induced tumor immunity and demonstrated significant improvement in median PFS (41.8 months(m) PCO vs 12.2 m PC, HR 0.46, p=0.0027) and median OS (N.E. PCO vs 43.2 m PC, HR O.35, p=0.043) in patients with previously untreated EOC. Oregovomab combined with PC had a favorable toxicity profile. FLORA-5/GOG3035, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Methods: The study is a phase 3, multicenter, double-blind, placebo-controlled trial. Optimally debulked patients with FIGO III/IV EOC and serum CA125 ≥ 50 U/ml receiving adjuvant (Cohort 1) or patients receiving neoadjuvant chemotherapy post-interval cytoreductive surgery (Cohort 2) will be randomized to PC + oregovomab or placebo (PCO vs. PCP). Patients with germline BRCA1/2 mutations are excluded. Chemotherapy will be administered every 3 weeks in both cohorts. Oregovomab/placebo is administered simultaneously at cycles 1, 3, and 5 of chemotherapy with an additional dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients will be administered oregovomab/placebo after debulking surgery at cycles 4 and 6 with two additional doses at 6- and 18-weeks following cycle 6 in Cohort 2. No other front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1. Cohort 1 will recruit 372 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.65 when 252 PFS events have been observed. Cohort 2 will be analyzed separately recruiting 232 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.60 when 165 PFS events have been observed. An interim futility analysis will be performed. Secondary objectives include OS, frequency and severity of AEs, and QoL. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of correlative biomarkers. The study is actively enrolling in the US, Canada, Belgium, Italy, Spain, Czech Republic, Hungary, Poland, Korea, Taiwan, Mexico, Argentina, and Chile. 179 patients were enrolled at time of submission. Clinical trial information: NCT04498117.

TPS5615 Background: Low-grade serous ovarian cancer (LGSOC) constitutes up to 10% of all ovarian cancer and has clinical and molecular characteristics distinct from high-grade serous ovarian cancer. Approximately a third of patients (pts) with recurrent LGSOC harbor KRAS mutations (mt) and pts with KRAS wild-type (wt) LGSOC may have mutations in NRAS, BRAF, or other RAS pathway-associated genes. Prior clinical studies with single agent MEK inhibitors have shown response rates of 16-26% in recurrent LGSOC. VS-6766 is a unique small molecule RAF/MEK clamp that inhibits both RAF and MEK activities by trapping them in inactive complexes. This mechanism of blockade has been shown to limit compensatory MEK activation, thereby potentially enhancing efficacy of MEK inhibition. Focal adhesion kinase (FAK) activation is a putative resistance mechanism to RAF and MEK inhibition, and defactinib, a small molecule inhibitor of FAK, has shown synergistic anti-tumor activity with VS-6766 in preclinical models, including organoids from LGSOC pts. Furthermore, FAK inhibition combined with VS-6766 induces tumor regression in a KRAS mt ovarian cancer xenograft model. The combination of VS-6766 and defactinib is currently being evaluated in the ongoing Investigator Sponsored FRAME study (NCT03875820). In this proof-of-concept study, durable objective responses (ORR = 46%; 11/24) have been reported in recurrent LGSOC pts, including pts who have had a prior MEK inhibitor (Banerjee ESMO 2021) and the combination of VS-6766 + defactinib has received FDA Breakthrough Therapy Designation for recurrent LGSOC. These initial preclinical and clinical results support the ongoing phase 2 ENGOT-ov60/GOG-3052 in recurrent LGSOC. Methods: This is an international phase 2, adaptive, multicenter, randomized, open label study designed to evaluate the efficacy and safety of VS-6766 vs VS-6766 in combination with defactinib currently open to enrollment (NCT04625270). The study will be conducted in two parts. Part A will determine the optimal regimen based on confirmed overall response rate (independent radiology review) in KRAS mt and KRAS wt LGSOC. Part B will determine the efficacy of the optimal regimen identified in Part A in KRAS mt and KRAS wt LGSOC. The minimum expected enrollment is 104 pts, 52 pts with KRAS mt and 52 KRAS wt (64 pts in Part A and 40 pts in Part B). Pts will be randomized to receive VS-6766 (4.0 mg orally (PO), twice weekly 3 wks on, 1 wk off) or VS-6766 with defactinib (VS-6766 3.2 mg PO, twice weekly + defactinib 200 mg PO BID 3 wks on, 1 wk off) till progression. Key inclusion criteria include histologically confirmed LGSOC, known KRAS mutation status, prior systemic therapy including platinum for metastatic disease and up to 1 prior line of MEK inhibitor therapy permitted. Part A of this study has completed enrollment and Part B is currently enrolling pts. Clinical trial information: NCT04625270.

Objectives: To report on the incidence of ovarian metastasis in patients with high grade neuroendocrine tumors of the cervix (NEC) who underwent surgical resection. Methods: This was a single institution retrospective chart review. The electronic medical record was searched for all patients with a diagnosis of NEC at The Ohio State University from January 2010 to March 2020. Patients without complete pathologic records were excluded. Results: From January 2010 to March 2020, 43 patients were identified with NEC. Of those patients, 16 had undergone surgical resection including hysterectomy, bilateral salpingectomy and oophorectomy, and lymph node dissection. Of the 16 patients, zero had evidence of metastatic disease to their ovaries. The median age of patients in our cohort was 35.5 years with a mean age of 40.5 (28-70y). 13 of the 16 patients were considered pre-menopausal at the time of their surgery (defined as age 50 or younger). Of the 16 patients who underwent surgical management, 2 had adjuvant chemotherapy alone, 7 had adjuvant chemotherapy with adjuvant radiotherapy, 2 had adjuvant chemoradiotherapy, and 3 had adjuvant radiation therapy. Of the 16 patients in the study, 13 received neoadjuvant chemotherapy as part of their treatment. For those who had chemotherapy as part of their treatment plan, the most commonly used regimen was cisplatin with etoposide with a median of 3 cycles neoadjuvant and 3 cycles in the adjuvant setting. Based on the FIGO 2018 staging classifications, 6 patients had stage I disease (1 1A2, 2 IB1, 1 IB2, 2 IB3). 10 of the 16 patients had advanced stage disease defined as IIB through IVB (2 IIB, 1 IIIB, 3 IIIC1, 2 IIIC2, 2 IVB). Conclusions: The incidence of ovarian metastasis in patients with NEC has not been reported in the literature. Here we demonstrate in our limited series that ovarian metastasis in NEC of the cervix is rare. Current practice of ovarian retention in NEC is based on expert opinion and is not standard of care across the field of gynecologic oncology. Our data support that ovarian retention in NEC is safe. Previously published data from our institution demonstrate that 82% of patients with stage I disease had no evidence of disease at time of their last follow up with the use of a multimodality treatment approach (McCann 2013). In our cohort, radiation therapy is often employed in the treatment of NEC. Ovarian retention with transposition out of the radiated field may be a reasonable option for women who would benefit from preservation of ovarian function. Commonly used chemotherapeutic agents were cisplatin with etoposide, both with limited gonadotoxicity. Given the low incidence of ovarian metastasis in NEC, ovarian cryopreservation or oocyte harvesting is a reasonable option for patients who desire the ability to have offspring with the assistance of a surrogate in the future. Further studies with a multi-institutional collaboration to better define the incidence of NEC metastasis to the ovary is necessary.

Objectives: The SARS-CoV-2 pandemic forced a shift in conducting clinical research. Ensuring the safety of all stakeholders (patients, research personnel, family members), maintaining financial viability, and overcoming operational restrictions (limited access to sites, workforce restrictions, reduced data collection) are barriers to continuing clnical research. GOG Partners, the GOG Foundation industry-sponsored clinical trials group, has been proactive to implement the following: 1) immediate compliance with CDC, FDA, and NIH guidelines with regard to clinical trial management; 2) systems that allowed for remote monitoring and other remote activities (telemedicine patient visits, remote data collection, shipping of drug to patients, virtual study start-up); 3) enhance enrollment opportunites away from university-based sites towards community-based practices; 4) increased frequency of our operations meetings with industry. The objective of this report is to describe how the pandemic affected accrual to GOG Partners’ trials. Methods: Accrual data for GOG Partners trials over the past 4 years (2017- July 2020) were collected. ‘Pandemic’ months were considered March thru July 2020. Information collected included accrual numbers, institution type (university versus non-university), and region of country. Descriptive statistics were analyzed. Results: Over the past 4 years, the median monthly accrual to GOG Partners trials was 43 patients (range: 14-95). Between March and July 2020, the median accrual was 59 patients (range: 43-72). For the same 5-month period over the past 3 years (March to July 2017, 2018, 2019) the median accrual was 36 (14-95). Accrual in March 2020 was 69 patients. Accrual decreased to 43 patients in April 2020 and 47 patients in May 2020 with respective z-scores of -0.25 and -0.01. June and July 2020 showed increased accrual with 59 and 72 patients respectively. The median number of participating sites per month over the past 4 years was 32 (9-66). There was an immediate decline in the number of sites participating from April to May 2020 of 36%. The number of sites participating in June and July were 38 and 52, respectively. During the pandemic, the accrual in the New England, Mid-Atlantic, Pacific and South Atlantic regions varied from their baselines. These variations followed the trends in COVID-19 spread. Non-university institutions accrued at a near-average rate throughout the months of April and May. During that same period, universities observed a decline in accrual of 48%. Conclusions: Accrual to GOG Partners’ trials increased 37% over the median monthly accrual since the pandemic began. During the pandemic, total monthly accrual fell below or reached the median during only 1 month. Regional diversity of sites participating in GOG Partners’ studies helped in preventing a more dramatic drop in participation. While overall accrual has historically shown to be relatively balanced between institution types, non-university institutions were less negatively impacted.

Objectives: To describe results of tumor testing among women with ovarian cancer and to identify associations with oncologic outcomes according to genetic variant status. Methods: Institutional review board (IRB)-approved, retrospective review of tumor genomic results obtained within a single Gynecologic Oncology division. Genomic results, oncologic outcomes and other clinicopathologic data points were abstracted from medical records. Platinum sensitivity and response to PARP inhibitors were compared between patients with: germline BRCA (gBRCA) pathogenic variants (PV), somatic BRCA (sBRCA) PVs and no gBRCA PVs, and loss of heterozygosity (LOH)/genome instability and no gBRCA or sBRCA PVs. These groups are referred to as “gBRCA,” “sBRCA,” and “LOH,” respectively. Results: A total of 261 patients with epithelial ovarian/fallopian tube/primary peritoneal cancer had tumor testing between 2017 and 2020. There were 26 (10%) gBRCA PV carriers [15 BRCA1, 11 BRCA2] identified, 48/261 (18%) tumors with only sBRCA PVs and 13/261 (5%) tumors with LOH and no gBRCA or sBRCA PVs. There were no significant differences in histologies between groups. Of the patients with gBRCA and sBRCA respectively, 85% and 69% were primary platinum sensitive and 8% and 17% were primary platinum resistant, respectively (p=0.40). The average number of platinum-based regimens used before platinum resistance developed was 2.67 for gBRCA (N=6), 2.18 for sBRCA (N=11), 3.2 for LOH (N=5). These groups were not significantly different (p=0.17).23/26 (88%) gBRCA, 32/48 (67%) sBRCA, and 10/13 (77%) LOH patients received PARP inhibitors (PARPi) for treatment. 3 gBRCA and 4 sBRCA patients received PARPi more than once. Median PFS for PARPi use in the frontline was 6 months compared to 5 months in the recurrent setting. There were no significant differences between PFS on PARPi in the upfront or recurrent setting. PFS for PARPi used in the recurrent setting for gBRCA was 8 months (95% CI: 4.6-11.5) and 6.5 months (95% CI: 3.4-9.6) for sBRCA compared to 4 months for LOH (95% CI: 0.74-7.26; p=0.33). Download : Download high-res image (97KB) Download : Download full-size image Conclusions: Twenty-eight percent of ovarian cancer patients had a gBRCA or sBRCA PVs. Platinum sensitivity is similar between patients with gBRCA, sBRCA and LOH groups, however, patients with gBRCA and LOH received slightly more lines of platinum than those with sBRCA. There was a trend towards lower PFS for PARPi used in the recurrent setting in the LOH group compared to gBRCA or sBRCA. These outcomes should be evaluated in a larger population to determine the reliability of LOH assays for predicting functional homologous recombination deficiency and susceptibility to PARPi in the primary or recurrent setting.

Objectives: Preclinical data demonstrated a synergistic and additive effect between rucaparib and taxanes in human sporadic ovarian and endometrial cancer cell lines, with cell line data demonstrating that RNA expression of FOLR1 (folate receptor alpha) positively correlates with BRCA mutation status and with being LOH high. The objective was to estimate the maximally tolerated dose (MTD) and to describe toxicities associated with MIRV and rucaparib in patients with recurrent endometrial and platinum resistant epithelial ovarian cancer. Methods: Patients had to have evidence of folate receptor α (FRα) expression by IHC (≥25% of tumor staining at ≥2+ intensity) on archival tissue or recent biopsy. Using a 3+3 design patients were given MIRV (4, 5, or 6 mg/kg IV every 3 weeks) and rucaparib PO BID (400 mg, 500 mg, or 600 mg) depending on the dose level. A total of 6 additional patients are being enrolled to the expansion cohort. Toxicities were recorded using CTCAE v4.03 and response was determined with imaging every 3rd cycle, using RECIST v1.1 criteria. Results: A total of 88 patients were screened for FRα expression. A total of 16 patients have been enrolled to date; 12 with ovarian cancer and 4 with endometrial cancer, all had high grade serous carcinoma. Median age was 64.5 (range 57-82) with 3 (range 1-9) prior lines of treatment (including 5 with prior PARP inhibitor). Six patients completed DL2 (5/500), however, 2 DLTs with both grade 3 fatigue, and no DLTs at DL1, let us to establish the phase 2 dose at DL1 (MIRV 5 mg/kg IV every 3 weeks and rucaparib 400 mg PO BID). Treatment related toxicities (all grades) occurring in ≥25% of patients included fatigue (73%), nausea (67%), blurred vision (60%), anemia (47%), anorexia (47%), mucositis (40%), ALT/AST elevated (40%), dry eyes (33%), vomiting (27%), thrombocytopenia (27%), weight loss (27%), leukopenia (27%), dysgeusia (27%). Grade ≥3 toxicities were fatigue (20%), pneumonitis (13%), anemia (13%), diarrhea (7%), cataract (7%), lymphopenia (7%), thrombocytopenia (7%), weight loss (7%), hypokalemia (7%). A total of 12 patients are currently evaluable for response (updated results will be presented if accepted); 5 (33%) partial response, 1 (7%) unconfirmed partial response, 6 (40%) stable disease. The ORR was 6/12 (50%). 44% (4/9) in ovarian cancer and 67% (2/3) in endometrial cancer. Median FRα expression was 80% (70 for PR, 95 for SD; range 30-100). Median PFS is 6.3 months with 95% CI (0.7, 13.8) months. Among 6 responses, 1 progressed, 1 died, 4 are censored, thus the median duration of response is not reached. Conclusions: Combination rucaparib and MIRV was tolerable with mostly manageable side effects. Encouraging activity was seen in this heavily pretreated population (including prior PARPi) of both endometrial and ovarian cancer. Notably, two patients developed pneumonitis (AESI for both agents) grade ≥3 after 14 and 24 cycles of treatment, respectively, each with a prolonged PR. Close monitoring for delayed side effects remains critically important especially in those with prolonged therapy.

Objectives: Dickkopf-1 (DKK1) modulates Wnt signaling, promotes tumor growth through a CKAP4-AKT signaling pathway and contributes to an immune suppressive tumor microenvironment. DKN-01 (D), a neutralizing DKK1 antibody has demonstrated safety and clinical activity in advanced gynecologic malignancies. Prior literature has reported an association of CTNNB1 mutations and an aggressive biology and shorter survival in endometrioid endometrial cancer. We previously demonstrated Wnt activating mutations were associated with higher DKK1 tumoral expression in advanced gynecologic malignancies. Methods: Pts with recurrent gynecologic cancers [endometrial (EEC), ovarian (EOC) and carcinosarcoma (MMMT)] were treated with D as monotherapy (mono) or in combination with paclitaxel (pac) in a phase 2 basket trial (NCT03395080) whereby ≥50% must have had a Wnt signaling alteration. Here we report on the subgroup of pts with Wnt activating mutations (CTNNB1, RNF43, APC). Clopper-Pearson confidence intervals were used to study the association of Wnt activating mutations with clinical benefit (CR, PR or SD); Kaplan-Meier estimates/Cox-PH models were used for analyses of progression free survival (PFS) and overall survival (OS). Results: A total of 111 pts enrolled; 52 pts treated with D mono; 59 pts treated with D + pac. Mean number of prior therapies was 3.6 (range 1, 11) and 3.9 (range 1, 10) for D mono and D + pac, respectively. A total of 108 pts (97%) with available genetics; 23 pts (21%) had Wnt activating mutations [CTNNB1 (n=17), RNF43 (n=5), APC (n=3)]. Wnt activating mutations were more common in EEC (n=17/54, 31%) than EOC (n=2/33, 6%) and MMMT (n=4/24, 17%). Median duration of treatment with D was 6 cycles in pts with Wnt activating mutations compared with 3 cycles for pts without Wnt activating mutations. A total of 15 of 23 (65%) evaluable pts with Wnt activating mutations had clinical benefit [1 PR, 14 SD; durable SD (> 4 months) in 11 of 14 pts (48%)] compared with 34 of 76 (45%) evaluable pts [1 CR, 2 PR, 31 SD; durable SD (> 4 months) in 12 of 31 SD pts (16%)] without Wnt activating mutations. All 4 pts with an objective response had a PIK3CA mutation. Pts with Wnt activating mutations had longer PFS [median 5.5 mos; 95% CI (1.8, 6.0)] and OS [median 22.2 mos; 95% CI (7.3, NE)] compared with pts without Wnt activating mutations [median PFS 2.0 mos; 95% CI (1.8, 3.1)] and OS (median 9.9 mos; 95% CI (6.9, 12.5)]. Download : Download high-res image (65KB) Download : Download full-size image Conclusions: D has single agent activity in a subgroup of pts with Wnt activating mutations, historically identified as a poor prognostic group, whereby they experienced greater clinical benefit and longer survival compared with pts without Wnt activating mutations. A notable finding was that all responding pts had PIK3CA mutations. This study is ongoing and updated results will be presented.

This cohort study examines changes in the rates of solitary alcohol and marijuana use among 12th grade students between 1976 and 2019.

Introduction/Background Dostarlimab is a humanised programmed death (PD)-1 receptor monoclonal antibody that blocks interaction with the PD-1 ligands, PD-L1 and –L2. GARNET is a phase 1 study assessing antitumour activity and safety of dostarlimab monotherapy in patients with advanced solid tumours. Methodology This multicentre, open-label, single-arm study is being conducted in 2 parts, dose escalation and expansion. Here we report on 2 independent expansion cohorts of patients with recurrent or advanced endometrial cancer (EC) that progressed on or after a platinum-based chemotherapy regimen. Assignment to cohort A1 (mismatch mutation repair deficient [dMMR] EC) or cohort A2 (mismatch mutation repair proficient [MMRp] EC) was determined by immunohistochemistry (IHC) testing. Patients received 500 mg dostarlimab intravenously once every 3 weeks for 4 cycles, then 1000 mg once every 6 weeks until disease progression, discontinuation or withdrawal. The primary endpoints are objective response rate (ORR) and duration of response (DOR) by blinded independent central review using RECIST version 1.1. Results In total, 126 dMMR and 145 MMRp pts identified by IHC were enrolled and dosed. Of these, 103 dMMR and 142 MMRp pts had measurable disease as baseline and sufficient follow-up time (6 months) for efficacy analyses, respectively. Patients that progressed prior to 6 months were included in the evaluable population. ORR for dMMR EC was 44.7%; ORR for MMRp EC was 13.4% (table 1). Median DOR and OS were not reached in either cohort. Overall, 15 pts (5.5%) discontinued treatment due a TRAE (5 dMMR, 10 MMRp). Safety by cohort and overall are shown in table 2. There were no deaths attributed to dostarlimab. Conclusion Dostarlimab demonstrated durable antitumour activity in both dMMR and MMRp advanced/recurrent EC. dMMR status by IHC was associated with a higher response rate. Dostarlimab demonstrated a notable disease control rate (35.2%; 2.1% complete response, 11.3% partial response, 21.8% stable disease) in patients with MMRp EC, which comprised a higher percentage of patients with Type II EC and is historically associated with a worse prognosis. No new safety signals were detected. These cohorts are the largest prospective evaluation of a PD-(L)1 therapy in EC to date. Disclosures Clinical trial registration: NCT02715284 This study was sponsored by GlaxoSmithKline, Waltham, MA, USA. Dr. Oaknin reports consulting and honoraria from AstraZeneca, Tesaro, Clovis, PharmaMar, and Roche. Dr. Gilbert reports honoraria from Meck, AstraZeneca, and Pfizer. Dr. Tinker reports grants and personal fees from AstraZeneca. Dr. Sabatier reports grants from EISAI and AstraZeneca; personal fees from Roche, Pfizer, Tesaro, Novartis and AstraZeneca; and non-financial support from Roche, Pfizer, AstraZeneca, and Amgen. Dr. O’Malley reports personal fees from Immunogen, Eisai, Agenus, GSK : Consultant/Advisory Board for Clovis, Ambry, Abbvie, Janssen/JJ Steering committee for Genentech/Roche and Merck; Institutional funding from Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, CERULEAN PHARMA, GOG Foundation, BMS, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., Inventiv Health Clinical, Iovance Biotherapeutics, Inc, and PRA International. Dr. Ghamande reports consulting fees from Seattle Genetics; speakers’ bureau fees from GSK; and institutional grants from GSK, Merck, Roche, Genentech, Takeda, Seattle Genetics, Advaxis, BMS, Clovis, Abbvie, and Tesaro. Dr. Pothuri reports grants, personal fees and non-financial support from GSK; Advisory Board fees from AstraZeneca and Clovis Oncology. Dr. Boni has nothing to disclose. Drs. Guo and Im are employees of GlaxoSmithKline.

Introduction/Background The PRIMA/ENGOT-OV26/GOG-3012 trial showed that niraparib significantly improves progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer (aOC) that responded to front-line platinum-based chemotherapy (hazard ratio, 0.62; 95% CI, 0.50–0.76). Based on these results, niraparib has been approved in the United States and the European Union for front-line maintenance treatment in patients with aOC. In this post hoc analysis, we report the efficacy of niraparib in patients with BRCA-mutated (BRCAm) aOC with an emphasis on efficacy and safety of fixed vs. individualized starting doses (FSD vs. ISD). Methodology In this double-blind, placebo-controlled, randomised phase 3 trial, patients with newly diagnosed, high-grade aOC who responded to platinum-based chemotherapy were randomised 2:1 to receive FSD of niraparib 300 mg orally once daily (QD) or placebo. The trial was amended to incorporate an ISD of 200 mg orally QD for patients with a body weight Results The intention-to-treat population comprised 733 randomised patients, of which 223 (30%) had BRCAm tumours. Of those, 144 (65%) received FSD and 79 (35%) received ISD. Niraparib provided a comparable PFS benefit over placebo in patients receiving both FSD (hazard ratio, 0.44; 95% CI 0.26–0.73) and ISD (hazard ratio 0.29; 95% CI 0.13–0.67). A PFS subgroup analysis by patient characteristics is shown in table 1. A summary of grade ≥3 selected adverse events is shown in table 2. Conclusion Niraparib significantly improved PFS when utilised as maintenance treatment after front-line therapy in patients with BRCAm aOC. Patients receiving FSD or ISD derived similar PFS benefit, while the ISD group showed an improved safety profile. Disclosures Dr. Graybill reports personal fees from GlaxoSmithKline. Dr. Redondo reports institutional research funding from PharmaMar, Roche, and Eisai; and advisory roles at PharmaMar, AstraZeneca, Tesaro, Roche, and Eisai. Dr. O’Malley reports personal fees from Immunogen, Eisai, Agenus, GlaxoSmithKline: Consultant/Advisory Board for Clovis, Ambry, Abbvie, Janssen/JJ Steering committee for Genentech/Roche and Merck; Institutional funding from Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, CERULEAN PHARMA, GOG Foundation, BMS, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., Inventiv Health Clinical, Iovance Biotherapeutics, Inc, and PRA International. Dr. Gupta is an employee of GlaxoSmithKline. Dr. Gonzalez-Martin reports personal fees and non-financial support from AstraZeneca; grant and personal fees from GlaxoSmithKline, Clovis Oncology, Roche Holding AG, Merck & Co., Inc., Genmab, INMUNOGEN, Pharma Mar, S.A., and Oncoinvent AS. Dr. Monk reports consulting and advisory role at Merck, GlaxoSmithKline, Roche/Genentech, AstraZeneca, Advaxiz, Cerulean Pharma, Amgen, Immunogen, NuCana BioMed, Clovis Oncology, Pfizer, Mateon Therapeutics, Precision Oncology, Perthera, Abbvie, Myriad Pharmaceuticals, Incyte, VBL Therapeutics, Takeda, Samumed, Oncomed, OncoSec, ChemoID, Geistlich Pharma, Eisai and Chemocare; Speakers’ bureau at Roche/Genentech, AstraZeneca, Janssen, Clovis Oncology and GlaxoSmithKline; Honoraria from Merck, GlaxoSmithKline, Roche/Genentech, AstraZeneca, Advaxis, Immunogen, NuCana BioMed, Clovis Oncology, Pfizer, Mateon Therapeutics, Precision Oncology, Pethera, Abbvie, Myriad Pharmaceuticals, Incyte, Janssen, Amgen, Genmab, Samumed, Takeda, VBL Therapeutics, Puma Biotechnology, Immunomedics, Conjupro Biotherapeutics, Agenus, OncoQuest, ChemoID, Geistlich Pharma, Eisai and Chemocare; and Research funding from Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, GlaxoSmithKline, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, and Nucana. Drs. Korach, Han, Cloven and Knudsen have nothing to disclose. Funding GlaxoSmithKline (Waltham, MA)

Introduction/Background Tumor Treating Fields (TTFields) are a non-invasive, antimitotic cancer therapy. The Phase 2 INNOVATE study demonstrated safety of TTFields/weekly paclitaxel in 31 PROC (platinum-resistant ovarian cancer) patients (Vergote Gyn Onc 2018); efficacy: median PFS 8.9 months, 25% partial response,71% clinical benefit and 61% 1-year survival rate. This phase 3 ENGOT-ov50/GOG-329/INNOVATE-3 study [NCT03940196] investigates TTFields plus weekly paclitaxel in PROC patients. Methodology Patients (N=540) will have PROC (RECIST V1.1) within 6 months of last platinum therapy with maximum of 2–5 prior lines of systemic therapy, ECOG 0–1 and no peripheral neuropathy >grade1. Patients with primary refractory disease will be excluded. Patients will be randomized 1:1 to weekly paclitaxel alone or weekly paclitaxel (starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle ) plus TTFields (200 kHz for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow-up will be performed q4w, with radiological follow-up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Secondary endpoints: PFS, objective response rate, AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median OS from 12 to 16 months (HR 0.75). Data Monitoring Committee (DMC) meeting (March 2020) concluded that data to-date showed no safety issues and recommended trial continuation. Results TiP N/A Conclusion TiP N/A Disclosures

Introduction/Background Niraparib is a poly(ADP-ribose) polymerase inhibitor approved for maintenance treatment of patients with newly diagnosed advanced or platinum-sensitive, recurrent ovarian cancer (OC). Niraparib is also approved in the United States for the treatment of patients with OC who received ≥3 lines of therapy and whose cancer is either BRCA mutated or homologous recombination deficient (HRd) platinum-sensitive disease. The PRIMA/ENGOT-OV26/GOG-3012 trial showed that niraparib significantly improves progression-free survival (PFS) in patients with newly diagnosed advanced OC that responded to first-line platinum-based chemotherapy (hazard ratio, 0.62; 95% CI, 0.50–0.76). Here we report the efficacy of niraparib in patients by BRCA wild-type (BRCAwt) status. Methodology This double-blind, placebo-controlled, phase 3 trial evaluated niraparib in patients with newly diagnosed, advanced, high-grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer with a complete response (CR) or partial response (PR) to first-line platinum-based chemotherapy. Patients were stratified by best response to the first-line chemotherapy (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination status (deficient/proficient and not determined). Patients were randomised 2:1 to receive either niraparib or placebo once daily. The primary endpoint of PFS, assessed by blinded independent central review, was analysed using a stratified log-rank test and Cox proportional hazards model and hierarchically tested in HRd patients, then the overall population. BRCA and HRd status were determined by tumour samples at screening via the myChoice® test (Myriad, Salt Lake City, Utah). The prespecified BRCAwt subgroup PFS analysis was performed using a stratified log-rank test and Cox proportional hazards model and using Kaplan-Meier methodology. BRCAwt subgroups included the intention-to-treat/BRCAwt (all patients who were homologous recombination not determined [HRnd]/BRCAwt, HRd/BRCAwt, and homologous recombination proficient [HRp]/BRCAwt); subgroup analyses on the HRd/BRCAwt and HRp/BRCAwt were performed. Results Of 733 randomised patients, 473 (64.5%) had BRCAwt tumours (74 patients had unknown BRCA status). Of these 473, 150 (31.7%) had HRd/BRCAwt tumours, 249 (52.6%) had HRp/BRCAwt tumours, and 74 (15.7%) had HRnd/BRCAwt tumours. Niraparib-treated patients with BRCAwt tumours had a clinically meaningful PFS benefit regardless of homologous recombination status (table 1). Conclusion Niraparib improved PFS when utilised as maintenance therapy after front-line treatment of OC in patients with BRCAwt tumours, including in the most difficult to treat subgroup of patients with BRCAwt and HRp tumours. Disclosures Dr. Braicu reports honoraria from AstraZeneca, Tesaro, GSK, Roche Pharma, Clovis and MSD; consulting or advisory roles at AstraZeneca, Tesaro, GSK, Roche Pharma, Clovis, MSD, Abbvie, Eisai, Immunogen, Takeda; institutional research funding from Roche Diagnostics and Takkeda; and travel, accommodation and expenses from Astra Zeneca, RochePharma, Clovis, and MSD. Dr. Pothuri reports grants, personal fees and non-financial support from GSK; Advisory Board fees from AstraZeneca and Clovis Oncology. Dr. Alejandro Perez-Fidalgo reports speaker fees from GSK, AstraZeneca, Clovis, and Roche; advisory fees from GSK, AstraZeneca, Clovis, Abilify Pharma, Clinigen, Roche, and Amgen; grant from GSK; and travel fees from AstraZeneca and Roche. Dr. O’Malley reports personal fees from Immunogen, Eisai, Agenus, GSK : Consultant/Advisory Board for Clovis, Ambry, Abbvie, Janssen/JJ Steering committee for Genentech/Roche and Merck; Institutional funding from Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, CERULEAN PHARMA, GOG Foundation, BMS, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., Inventiv Health Clinical, Iovance Biotherapeutics, Inc, and PRA International. Dr. Graybill reports personal fees from GSK. Dr. Dahlstrand reports personal fees from AstraZeneca and Roche. Dr. Monk reports consulting and advisory role at Merck, GSK, Roche/Genentech, AstraZeneca, Advaxiz, Cerulean Pharma, Amgen, Immunogen, NuCana BioMed, Clovis Oncology, Pfizer, Mateon Therapeutics, Precision Oncology, Perthera, Abbvie, Myriad Pharmaceuticals, Incyte, VBL Therapeutics, Takeda, Samumed, Oncomed, OncoSec, ChemoID, Geistlich Pharma, Eisai and Chemocare; Speakers’ bureau at Roche/Genentech, AstraZeneca, Janssen, Clovis Oncology and GSK; Honoraria from Merck, GSK, Roche/Genentech, AstraZeneca, Advaxis, Immunogen, NuCana BioMed, Clovis Oncology, Pfizer, Mateon Therapeutics, Precision Oncology, Pethera, Abbvie, Myriad Pharmaceuticals, Incyte, Janssen, Amgen, Genmab, Samumed, Takeda, VBL Therapeutics, Puma Biotechnology, Immunomedics, Conjupro Biotherapeutics, Agenus, OncoQuest, ChemoID, Geistlich Pharma, Eisai and Chemocare; and Research funding from Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, GSK, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, and Nucana. Drs. Honhon and Fabbro have nothing to disclose. Dr. Gupta is an employee of GlaxoSmithKline.

Given the promise of the web push plus e-mail survey design for providing cost-effective and high-quality data (Patrick et al. 2018, 2019) as an alternative to a paper-and-pencil mailed survey design for the longitudinal Monitoring the Future (MTF) study, the current study sought to further enhance the web push condition. The MTF sample is based on US nationally representative samples of 12th grade students surveyed annually. The MTF control group for the current study included participants who completed the in-school baseline survey in the 12th grade and were selected to participate in their first follow-up survey in 2017 via mailed surveys (N = 1,222). A supplementary sample (N = ∼2,450) was assigned to one of the two sequential mixed-mode conditions. Those in condition 1 (N = 1,198), or mail push, were invited to complete mailed surveys and later given a web survey option. Those in condition 2 (N = 1,173), or enhanced web push, were invited to complete a web survey (the same as in the 2014 study, but with the addition of text messages and quick response (QR) codes and the web survey was optimized for mobile devices) and then later given a mailed survey option. Research aims were to examine response rates across conditions, as well as how responses were distributed across mode (paper, web), devices (computer, smartphone, table), and method of accessing the web survey (hand-entered URL, QR code, e-mail link, SMS link). Response rates differed significantly: the MTF control group was 34.2 percent, mail push was 35.4 percent, and enhanced web push was 42.05 percent. The higher response rate in the enhanced web push condition suggests that the additional strategies were effective at bringing in more respondents. Key estimates produced by the enhanced web push condition did not differ from those of the MTF control group.

Background The phenomenon of pseudoprogression (PsP) may appear with cancer immunotherapy. The underlying etiology is not fully elucidated, tumor flare is the suspected mechanism of early pseudoprogression that may resolve gradually while continuing treatment. Further, immunotherapy-induced sarcoidosis may mimic PsP. Here we present examples of 3 observed patterns of PsP in cervical cancer (CC) patients treated with balstilimab (BAL; anti-PD-1), alone or in combination with zalifrelimab (ZAL; anti-CTLA-4). Methods The evaluated patients received either BAL 3 mg/kg every 2 weeks alone (NCT03104699) or in combination with ZAL dosed at 1 mg/kg every 6 weeks (NCT03495882). PsP was defined as radiologic disease progression per RECIST1.1 followed by a significant reduction of measurable baseline lesions, disappearance of the non-measurable lesions, or no further progression for at least two tumor assessments after initial progressive disease (PD) by Independent Evaluation Review Committee (IERC). PsP was divided into 3 categories – early (before or at week 12 of treatment), delayed (after week 12) and serial (at least 2 PsP occurrences). Results Overall, 313 patients with post-chemotherapy recurrent CC with baseline measureable disease were treated with either BAL (n=160) or in combination with ZAL (n=143). Early PsP was observed in 7 patients treated with BAL and 8 with BAL/ZAL while 5 patients experienced delayed PsP (BAL (n=1); ZAL(n=4)). Serial PsP was observed in 1 patient (BAL only) and another (n=1) BAL treated experienced showed PsP (new Mediastinal lesions) present in 2 consecutive CT scan evaluations before disappearance – hence were classified as PD even by iRECIST. Immune-related sarcoidosis was confirmed histologically in 2 patients following confirmation by mediastinal lymph node biopsy. PsPs were accompanied with clear clinical benefit of disease improvement and weight stabilization, improvement in performance status, and decreased painPsP BAL (N=160)) BAL/ZAL (N=143)Early 7 (4%) 8 (6%)Delayed 1 ( Conclusions This is the first report of PsP in CC population. PsP-confounded IERC evaluation of tumor response was seen in some CC patients treated with BAL or combination of BAL and ZAL. The differentiation of PD and PsP has important consequences for disease assessment in clinical trials and disease management and outcomes. Further efforts to elucidate the underlying mechanisms and clearly define the characteristics of PsP are crucial for better treatment management of affected patients. Standard response evaluation systems including iRECIST may need further refinement to recognize the importance of PsP. Trial Registration NCT03104699 and NCT03495882 Ethics Approval C-700-01 : The WIRB Study # is 1173375 and the site IRB approval # is 20170314. and for C-550-01: ICON Cancer Center in South Brisbane, Queensland, Australia.- IRB approval # is 2017-10-766.

Introduction STRO-002 is a novel FRα-targeting ADC that delivers SC209, a potent tubulin-targeting hemiasterlin cytotoxin-warhead. Methods All patients in the ongoing dose escalation study (NCT03748186) had platinum resistant/refractory OC without selection for FRα expression. STRO-002 is given IV on Day 1 of each 21-day cycle. Results 38 patients have been dosed at 9 dose levels (0.5 to 6.4 mg/kg). Median number of cycles given is 3 (1–18). Median age is 61 (48–79). Median prior therapies - 5 (2–10). Clinically active doses (≥ 2.9 mg/kg) have been administered to 33 patients. 21/33 (64%) remain on treatment. Partial response was seen in 5 of 29 evaluable patients (17%) with 2 confirmed on second scan. 9 pts have confirmed SD for a clinical benefit rate of 48% (14/29). CA125 reduction of >50% was seen in 14/22 (64%) evaluable patients per GCIG. Clinical activity appears to be durable with 36% and 24% on study >16 and >24 weeks, respectively. 88% of AEs are grade 1 or 2. Grade 3–4 neutropenia, an expected and reversible effect of STRO-002 occurred in 15/38 (39%). DLTs reported – grade 3 neuropathy (6.0 mg/kg) and grade 3 bone pain (6.4 mg/kg). Conclusions STRO-002 is a novel FRα-targeting ADC with a promising emerging safety and efficacy profile and preliminary clinical benefit/disease control rate of 48% in patients with relapsed/refractory OC treated at ≥ 2.9 mg/kg. No ocular toxicity signals have been observed, suggesting potential differentiation from other FRα-targeting investigational therapies. Expansion cohorts in less heavily pre-treated patients are planned for 4Q20.

Introduction Niraparib is a poly(ADP-ribose) polymerase inhibitor approved for maintenance treatment of patients with newly diagnosed or recurrent OC that responded to platinum-based chemotherapy and treatment in heavily-pretreated recurrent OC. Here we report efficacy in patients receiving the FSD and ISD in the PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016). Methods This double-blind, placebo-controlled, phase 3 study randomized 733 patients to receive niraparib or placebo for 36 months or until disease progression/toxicity. A protocol amendment introduced ISD: 200 mg in patients with body weight Results BICR and IA PFS were highly concordant in the overall population. Efficacy of niraparib based on IA PFS in FSD vs ISD subgroups for each data cut were similar (table 1). Dose interruptions, modifications, and hematologic toxicity were lower with the ISD. Exposure–response data supported the clinical data. Conclusions The 200- or 300-mg ISD by baseline body weight and platelet counts demonstrated comparable efficacy while improving the safety profile of niraparib. Use of this regimen for first-line maintenance of advanced OC patients is approved by the US FDA. Funded by: GlaxoSmithKline NCT: NCT02655016

Background Tumor Treating Fields (TTFields) are a non-invasive, antimitotic cancer therapy. The Phase 2 INNOVATE study demonstrated safety of TTFields/weekly paclitaxel in 31 PROC (platinum-resistant ovarian cancer) patients (Vergote Gyn Onc 2018); efficacy: median PFS 8.9 months, 25% partial response,71% clinical benefit and 61% 1-year survival rate. This phase 3 ENGOT-ov50/GOG-329/INNOVATE-3 study [NCT03940196] investigates TTFields plus weekly paclitaxel in PROC patients. Study Design Patients (N=540) will have PROC (RECIST V1.1) within 6 months of last platinum therapy with maximum of 2–5 prior lines of systemic therapy, ECOG 0–1 and no peripheral neuropathy >grade1. Patients with primary refractory disease will be excluded. Patients will be randomized 1:1 to weekly paclitaxel alone or weekly paclitaxel (starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle ) plus TTFields (200 kHz for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow-up will be performed q4w, with radiological follow-up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Secondary endpoints: PFS, objective response rate, AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median OS from 12 to 16 months (HR 0.75). Data Monitoring Committee (DMC) meeting (March 2020) concluded that data to-date showed no safety issues and recommended trial continuation.

Introduction In ARIEL3 (NCT01968213), rucaparib maintenance for recurrent ovarian cancer (rOC) significantly improved investigator-assessed PFS and postprogression efficacy outcomes versus placebo regardless of biomarker status. PFS was also improved in patients with rOC associated with either BRCA1 or BRCA2 mutations (HR, 0.32 [95% CI, 0.19–0.53] and 0.12 [0.06–0.26], respectively). This exploratory analysis further examined the subgroup of patients with rOC associated with BRCA1 or BRCA2 mutations to assess the durability of the clinical benefit of rucaparib maintenance following disease progression. Methods Patients were randomised 2:1 to oral rucaparib (600 mg twice daily) or placebo. Postprogression efficacy endpoints were assessed in patients with germline or somatic BRCA1 or BRCA2 mutations. Results Investigator-assessed postprogression efficacy endpoints for patients with either BRCA1 or BRCA2 mutations are presented in the table 1. There was a trend for better outcomes across all endpoints in patients with BRCA1 and BRCA2 mutations, with larger differences between the median values among patients with a BRCA2 mutation. The treatment-by-mutation group interaction test reached statistical significance for TFST and CFI. Among rucaparib-treated patients, the most common treatment-emergent adverse events (any grade) in the BRCA1 and BRCA2 subgroups were nausea (81.0% and 78.0%) and asthenia/fatigue (74.7% and 80.0%). Conclusions/Implications All postprogression efficacy endpoints were longer with rucaparib maintenance than with placebo in both BRCA-mutant subgroups. Safety data for the two subgroups were similar and were consistent with the overall safety population.

The self-assembly of amphiphilic diblock copolymers into polymeric vesicles, commonly known as polymersomes, results in a versatile system for a variety of applications including drug delivery and microreactors. In this study, we show that the incorporation of hydrophobic plasmonic nanoparticles within the polymersome membrane facilitates light-stimulated release of vesicle encapsulants. This work seeks to achieve tunable, triggered release with non-invasive, spatiotemporal control using single-pulse irradiation. Gold nanoparticles (AuNPs) are incorporated as photosensitizers into the hydrophobic membrane of micron-scale polymersomes and the cargo release profile is controlled by varying the pulse energy and nanoparticle concentration. We have demonstrated the ability to achieve immediate vesicle rupture as well as vesicle poration resulting in temporal cargo diffusion. Additionally, changing the pulse duration, from femtosecond to nanosecond, provides mechanistic insight into the photothermal and photomechanical contributors that govern membrane disruption in this polymer&ndash, nanoparticle hybrid system.

OBJECTIVE: This study estimated the percentage of age 35 and 55 adults reporting using medical marijuana intended for someone else (diverted use) and compared demographics and health status of such users with respondents reporting recommended use (i.e., individuals with a medical marijuana recommendation for their own health conditions) and to respondents using marijuana not intended for medical use (nonmedical marijuana [NMM] use). METHOD: Cross-sectional analyses were conducted using complex sample survey data collected from 2013 to 2018 from 12,138 adults (6,998 women) at modal ages 35 or 55 participating in the U.S. national Monitoring the Future study. RESULTS: Diverted use was reported by 72.9% [95% CI, 66.4, 79.4] and 64.3% [56.0, 72.7] of age 35 and 55 past-12-month medical marijuana users, respectively. Age 35 diverted users were more likely than recommended users to not work full time and have no postsecondary education. Age 55 recommended users were more likely than NMM users to be retired. Age 35 diverted users were less likely than recommended users to report poor physical health (odds ratio [OR] = 0.40 [0.17, 0.94]). Age 55 diverted users were less likely than recommended users to report three or more poor health conditions (OR = 0.22 [0.09, 0.55]) and any qualifying conditions (OR = 0.21 [0.08, 0.58]). Prevalence of these conditions was similar between diverted and NMM users. CONCLUSIONS: Results indicated a substantial degree of nonmedical (i.e., recreational) marijuana use. Diverted and NMM users reported generally similar levels of health conditions, whereas diverted users had fewer indicators of poor health than recommended users.

PURPOSE Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.

Background Cryoablation of the posterior nasal nerve at the middle meatus has been shown to successfully treat nasal obstruction and symptoms of chronic rhinitis. Cryoablation of both the middle and inferior meatus has not yet been studied. Objectives To evaluate the safety and feasibility of cryoablation of the posterior nasal nerve at both the middle and inferior meatus locations to treat chronic rhinitis. Methods Participants underwent bilateral cryoablation of the posterior nasal nerve at both the middle meatus and inferior meatus and were assessed through 3 months post treatment. The primary endpoint is the change from baseline to 3-month follow-up in the reflective Total Nasal Symptom Score (rTNSS). Other assessments include additional patient-reported outcomes, physician assessment, and independent review and scoring of imaging. Results Thirty participants were enrolled at 3 US centers. There was a significant improvement from baseline in the median rTNSS (–4.0, P Conclusion Cryoablation at both the middle meatus and inferior meatus appears to be a safe and feasible option for treatment of chronic rhinitis. In this feasibility study, there is significant improvement in symptoms post treatment. Adverse events are minor and transient.

Blended biocomposites created from the electrostatic and hydrophobic interactions between polysaccharides and structural proteins exhibit useful and unique properties. However, engineering these biopolymers into applicable forms is challenging due to the coupling of the material&rsquo, s physicochemical properties to its morphology, and the undertaking that comes with controlling this. In this particular study, numerous properties of the Bombyx mori silk and microcrystalline cellulose biocomposites blended using ionic liquid and regenerated with various coagulation agents were investigated. Specifically, the relationship between the composition of polysaccharide-protein bio-electrolyte membranes and the resulting morphology and ionic conductivity is explored using numerous characterization techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray scattering, atomic force microscopy (AFM) based nanoindentation, and dielectric relaxation spectroscopy (DRS). The results revealed that when silk is the dominating component in the biocomposite, the ionic conductivity is higher, which also correlates with higher &beta, sheet content. However, when cellulose becomes the dominating component in the biocomposite, this relationship is not observed, instead, cellulose semicrystallinity and mechanical properties dominate the ionic conduction.

Current grading systems for platinum hypersensitivities (pHSR) rely on subjective features rather than objective clinical signs leading to inconsistencies in grading. To standardize classification of pHSR, a clinical grading system was developed at our institution. We report the clinical outcomes our classification system and evaluate its correlation with the classification systems currently published and used in practice.This was a retrospective review of patients with pHSR from 2011 to 2017. Demographics, chemotherapeutic histories (CT), and details of their initial HSR were collected. Mild reactions were defined as local skin manifestations only. Moderate-low reactions included widespread skin, respiratory or GI findings. Moderate-standard reactions were defined as transient cardiovascular compromise (CVC), hypoxia or neurologic changes whereas sustained changes (10 min) were used to define severe reaction. Fischer Exact Tests (p .05) and binary logistic regression analyses were performed. Spearman correlation were used to assess relationships between our grading system and the NCCN and CTCAEv4.0 criteria.87 patients were identified with most having ovarian cancer (n = 55, 63.2%), receiving carboplatin (n = 62, 71.3%), and on second-line CT (n = 34, 42.5%). Chest pain was associated with transient CVC (OR 10.0, 95% CI 1.148-87.133) while nausea/vomiting (OR 8.420, 95% CI 1.263-55.275) was associated with transient hypoxia albeit less closely than transient hypotension (OR 17.010, 95% CI 2.026-142.825). Only presyncope/syncope remained associated with sustained CVC (OR 38.0, 95% CI 2.815-512.912) on logistic regression. The classification system was most strongly correlated with the NCCN grading system (ρ 0.761, p .001).This classification system offers an objective means of grading pHSR severity and correlates with currently-used grading systems.

Purpose: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/paclitaxel (C/P), is recognized as an alternative in treating advanced/recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002. Patients and Methods: Eligible patients had stage III to IV or recurrent disease. Participants were randomized 1:1 to receive C/P for six cycles ± T followed by maintenance T until progression or toxicity. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and toxicity were secondary endpoints. Results: Sixty-one patients were randomized. After a median-follow-up of 25.9 months, 43 progressions and 38 deaths occurred among 58 evaluable patients. Updated median-PFS continued to favor the T-arm, with medians of 8.0 months versus 12.9 months in the control and T-arms (HR = 0.46; 90% CI, 0.28–0.76; P = 0.005). Median-PFS was 9.3 months versus 17.7 months among 41 patients with stage III to IV disease undergoing primary treatment (HR = 0.44; 90% CI, 0.23–0.83; P = 0.015), and 7.0 months versus 9.2 months among 17 patients with recurrent disease (HR = 0.12; 90% CI, 0.03–0.48; P = 0.004). OS was higher in the T compared with the control arm, with medians of 29.6 months versus 24.4 months (HR = 0.58; 90% CI, 0.34–0.99; P = 0.046). The benefit was most notable in those with stage III to IV disease, with survival median not reached in the T-arm versus 24.4 months in the control arm (HR = 0.49; 90% CI, 0.25–0.97; P = 0.041). Toxicity was not different between arms. Conclusions: Addition of T to C/P increased PFS and OS in women with advanced/recurrent HER2/Neu-positive USC, with the greatest benefit seen for the treatment of stage III to IV disease.

Background More United States adolescents now report high-frequency marijuana use than similar use levels of alcohol or tobacco. Increased high-frequency use raises questions such as (a) is frequent use likelihood growing among adolescents who experiment with use? (b) Is such change observed equally across sex and racial/ethnic subgroups? (c) Have sociodemographic and other covariate associations with frequent use changed over time? Methods Data were obtained from 649,505 12th grade students participating in the cross-sectional, nationally-representative Monitoring the Future study from 1976 to 2019. Historical trends were modeled for any and frequent (20+ occasions) past 30-day marijuana use among all students and lifetime users, and lifetime user sex and racial/ethnic subgroups. Multivariable logistic regression estimates from 1989 to 1993 (lowest prevalence years) versus 2015−2019 (most recent years) were compared to examine covariate association changes with frequent use. Results Among all students, recent linear trends in any and frequent marijuana use were not significantly different from zero (0.023 [SE 0.156] and 0.036 [0.073], respectively); frequent use among lifetime users increased (0.233 [0.107], p = 0.048). Among lifetime users, the increase was stronger for male than female students, and for minority versus White students. Significant association changes with race/ethnicity, parental education, and perceived risk were observed. Conclusions The proportion of adolescent lifetime marijuana users reporting current frequent marijuana use increased, and is now at near-record levels. Increases were particularly strong among males and minority students. There appears to be an increasing likelihood that adolescents who experiment with marijuana use may progress to frequent use.

Pacients d'edat avançada; Càncer d'ovaris; Inhibidor de la PARP Pacientes de edad avanzada; Cáncer de ovarios; Inhibidor de PARP Elderly patients; Ovarian cancer; PARP inhibitor Background In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3. Methods Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo. Exploratory, post hoc analyses of progression-free survival (PFS), patient-centered outcomes (quality-adjusted PFS [QA-PFS] and quality-adjusted time without symptoms or toxicity [Q-TWiST]), and safety were conducted in three age subgroups (