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Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer. Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1–2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed. Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia. This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations. • Mirvetuximab soravtansine (MIRV) is an FDA-approved antibody-drug conjugate that targets folate receptor alpha (FRα). • The confirmed objective response rate was 83% (n = 34/41; 95% CI, 68–93), including 9 complete and 25 partial responses. • Tumor regression occurred in 40/41 participants with FRα expression ≥50%; median progression-free survival was 13.5 months. • Grade ≥3 treatment-related thrombocytopenia and neutropenia occurred in 51% and 44% of participants, respectively. • Treatment-emergent adverse events led to 24 discontinuations (any drug); thrombocytopenia led to most dose modifications. [ABSTRACT FROM AUTHOR]

This study investigated the safety and tolerability of lifastuzumab vedotin (DNIB0600A) (LIFA), an antibody-drug conjugate, in patients with recurrent platinum-sensitive ovarian cancer (PSOC). In this open-label, multicenter phase 1b study, LIFA was administered intravenously once every 3 weeks (Q3W) with starting dose 1.2 mg/kg in a 3 + 3 dose-escalation scheme. All patients received carboplatin at dose AUC 6 mg/mL·min (AUC6) Q3W for up to 6 cycles. Dose expansion cohorts were enrolled ± bevacizumab 15 mg/kg Q3W. Patients received LIFA at 1.2, 1.8, and 2.4 mg (n = 4, 5, and 20, respectively) with carboplatin. The maximum tolerated dose was not reached. The recommended phase 2 dose (RP2D) was LIFA 2.4 mg/kg + carboplatin AUC6 (cycles 1–6), with or without bevacizumab 15 mg/kg. Twelve patients received RP2D with bevacizumab. All patients experienced ≥1 adverse event (AE). The most common treatment-related AEs were neutropenia, peripheral neuropathy, thrombocytopenia, nausea, fatigue, anemia, diarrhea, vomiting, hypomagnesaemia, aspartate aminotransferase increased, alanine aminotransferase increased, and alopecia. Thirty-four (83%) patients experienced grade ≥ 3 AEs, the most frequent of which were neutropenia and thrombocytopenia. Nine (22%) patients experienced serious AEs. Pulmonary toxicities (34%), considered a potential risk of LIFA, included one patient who discontinued study treatment due to grade 2 pneumonitis. The median duration of progression-free survival was 10.71 months (95% CI: 8.54, 13.86) with confirmed complete/partial responses in 24 (59%) patients. Pharmacokinetics of mono-therapy LIFA was similar in combination therapy. LIFA in combination with carboplatin ± bevacizumab demonstrated acceptable safety and encouraging activity in PSOC patients. • Lifastuzumab vedotin DNIB0600A (LIFA) is an anti-NaPi2b antibody conjugated to a potent anti-mitotic agent (MMAE). • This phase Ib study investigated LIFA in patients with recurrent platinum-sensitive ovarian cancer. • LIFA in combination with carboplatin has an acceptable safety profile when administered by IV infusion Q3W. • Overall confirmed objective responses were observed in 59% and CA-125 responses in 81% of evaluable patients. • Response rate and duration of response are important factors for evaluation of antibody-drug conjugates in ovarian cancers. [ABSTRACT FROM AUTHOR]

Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1–2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1–21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). National Cancer Institute. • The PARP inhibitor veliparib can be combined with chemotherapy. • A feasible combination dose was accomplished without compromised dose intensity. • Combination veliparib and chemotherapy may improve responses in front line treatment. [ABSTRACT FROM AUTHOR]

Abstract Objective To analyze the safety and efficacy of niraparib in patients aged ≥70 years with recurrent ovarian cancer in the ENGOT-OV16/NOVA trial. Methods The trial enrolled 2 independent cohorts with histologically diagnosed recurrent ovarian, fallopian tube, or peritoneal cancer who responded to platinum rechallenge, on the basis of germline breast cancer susceptibility gene mutation (g BRCA mut) status. Patients were randomized 2:1 to receive niraparib (300 mg) or placebo once daily until disease progression. The primary endpoint was progression-free survival (PFS) by blinded independent central review. Adverse events (AEs) of special interest were based on the known safety profile of poly(ADP-ribose) polymerase inhibitors. Results Patients aged ≥70 years in the g BRCA mut cohort receiving niraparib (n = 14) had not yet reached a median PFS compared with a median PFS of 3.7 months for the same age group in the placebo arm (hazard ratio [HR], 0.09 [95% confidence interval (CI), 0.01 to 0.73]). Non-g BRCA mut patients aged ≥70 years receiving niraparib (n = 47) had a median PFS of 11.3 months compared with 3.8 months in the placebo arm (HR, 0.35 [95% CI, 0.18 to 0.71]). Median duration of follow-up in the niraparib arm was 17.3 months in patients ≥70 years and 17.2 months in patients <70 years. Frequency, severity of AEs, and dose reductions in the niraparib arm were similar in patients aged <70 and ≥ 70 years population. The most common grade ≥ 3 AEs in patients ≥70 years were hematologic: thrombocytopenia event (34.4%), anemia event (13.1%), and neutropenia event (16.4%). Conclusions For patients ≥70 years of age receiving niraparib as maintenance treatment in the ENGOT-OV16/NOVA trial, PFS benefits and incidence of any grade or serious treatment-emergent AEs were comparable to results in the younger population. Use of niraparib should be considered in this population. Highlights • Safety and efficacy of niraparib in pts. ≥70 years are similar to younger population. • Niraparib significantly prolongs PFS in g BRCA mut and non-g BRCA mut pts. ≥70 years. • Rates of myelosuppressive adverse events were similar in the <70 and ≥70 age groups. [ABSTRACT FROM AUTHOR]

Abstract Purpose To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients. Methods Patients with recurrent, platinum-sensitive epithelial ovarian or fallopian tube cancer were enrolled. Eligibility included a minimum requirement of tumor FRα positivity (≥25% of cells with ≥2+ staining intensity). Patients received escalating doses of mirvetuximab soravtansine and carboplatin on day 1 of a 21-day cycle (once every 3 weeks). Mirvetuximab soravtansine maintenance therapy was permitted, at the investigators discretion, following cessation of carboplatin treatment. Adverse events, tumor response, and progression-free survival (PFS) were determined. Results Eighteen patients were enrolled and dosed with combination therapy; thirteen continued with mirvetuximab soravtansine maintenance following carboplatin discontinuation. Mirvetuximab soravtansine dosing was escalated from 5 to 6 mg/kg (adjusted ideal body weight) and carboplatin from AUC4 to AUC5. Adverse events were generally mild (≤ grade 2) with nausea, diarrhea, thrombocytopenia, blurred vision, and fatigue being the most common treatment-emergent toxicities. For all evaluable patients (n = 17), the confirmed objective response rate (ORR) was 71%, including three complete responses and nine partial responses, and the median PFS was 15 months. A median duration of response was not reached. Conclusion These data demonstrate that mirvetuximab soravtansine combined with carboplatin is a well-tolerated and highly active regimen in recurrent, platinum-sensitive ovarian cancer. Further evaluation of this combination in a randomized fashion is warranted. Highlights • Combining mirvetuximab soravtansine and carboplatin is a promising approach for platinum-sensitive ovarian cancer. • The combination was well tolerated; low incidence of severe hematologic/neuropathic toxicities, and no new safety signals. • A highly active regimen, with a confirmed objective response rate of 71%. • Better median PFS (15 months) compared to historical carboplatin plus chemotherapy phase III trials. [ABSTRACT FROM AUTHOR]

Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. The mechanisms of action of niraparib include inhibition of PARP enzymatic activity as well as increased formation of PARP-DNA complexes through “trapping” the PARP enzyme on damaged DNA. Phase I and III studies have demonstrated activity and benefit of niraparib in both BRCA mutated ( BRCA m) and BRCA wild-type ( BRCA wt) cancers. Phase I testing of niraparib established the maximally tolerated dose of 300 mg by mouth (PO) daily, and the phase 3 ENGOT-OV16/NOVA study demonstrated the benefit of niraparib maintenance therapy compared to placebo after completion of and response to platinum-based chemotherapy in both BRCA m and BRCA wt ovarian cancer patient populations. Toxicities seen with niraparib include hematologic, gastrointestinal, fatigue, and cardiovascular. Hematologic toxicities include thrombocytopenia, anemia, neutropenia and leukopenia; upfront dose modification to 200 mg niraparib for patients with baseline weight of ≤77 kg and/or baseline platelets of ≤150,000 K/uL should be considered to avoid significant hematologic toxicity, especially thrombocytopenia, based on recent analyses of the ENGOT-OV16/NOVA study. Cardiovascular toxicities include hypertension, tachycardia, as well as palpitations, and patients should be monitored for hypertension. PARP inhibitors have been associated with low risks of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), and the overall risk of AML and MDS is 0.9% of all patients treated with niraparib. Niraparib testing is ongoing in newly diagnosed ovarian cancer patients as maintenance therapy following completion of platinum-based chemotherapy, in BRCA wt cancers as treatment, as well as in combinations with other biologic drugs such as immunotherapy and anti-angiogenic agents. [ABSTRACT FROM AUTHOR]

Objective This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC. Methods Patients enrolled in GOG-172 and 182 who provided specimens for translational research and consent were included. Germline DNA was evaluated with the Illumina's HumanOMNI1-Quad beadchips and scanned using Illumina's iScan optical imaging system. SNPs with allele frequency > 0.05 and genotyping rate > 0.98 were included. Analysis of SNPs for PFS and OS was done using Cox regression. Statistical significance was determined using Bonferroni corrected p -values with genomic control adjustment. Results The initial GWAS analysis included 1,124,677 markers in 396 patients. To obtain the final data set, quality control checks were performed and limited to serous tumors and self-identified Caucasian race. In total 636,555 SNPs and 289 patients passed all the filters. The pre-specified statistical level of significance was 7.855e − 08 . No SNPs met this criteria for PFS or OS, however, two SNPs were close to significance (rs10899426 p -2.144e − 08 ) (rs6256 p -9.774e − 07 ) for PFS and 2 different SNPs were identified (rs295315 p -7.536e − 07 ; rs17693104 p -7.734e − 07 ) which were close to significance for OS. Conclusions Using the pre-specified level of significance of 1 × 10 − 08 , we did not identify any SNPs of statistical significance for OS or PFS, however several were close. The SNP's identified in this GWAS study will require validation and these preliminary findings may lead to identification of novel pathways and biomarkers. [ABSTRACT FROM AUTHOR]

Objective To characterize patients who did not enroll on a clinical trial and identify barriers that may limit enrollment among patients with advanced epithelial ovarian cancer (EOC) presenting for first-line chemotherapy. Methods We conducted a retrospective review of patients diagnosed with stage II-IV EOC from 10/2009–4/2013, a time period during which multiple trials were available to all EOC patients, including optimally debulked, suboptimally debulked, or undergoing neoadjuvant chemotherapy. Enrollment status, demographics, tumor characteristics, and treatment details were recorded. SAS version 9.3 was used for all analyses. Results 144 patients met study criteria; 67% were enrolled on a trial. Enrolled patients were significantly younger (median 61 vs 68 years, p = 0.002). Stage ( p = 0.30), race ( p = 0.75), and performance status ( p = 0.38) were similar between enrolled and non-enrolled patients. Distance did not impact enrollment, as nearly half of patients in both groups lived > 50 miles from the treatment center (39.0% vs 47.8%, p = 0.36). Mode of chemotherapy administration significantly differed based on participation (all p < 0.05). Despite similar residual disease status ( p = 1.00) and number of chemotherapy regimens received ( p = 0.59), patients treated on trial had a higher 3-year survival rate (70.7% vs 51.7%, p = 0.031). The difference in median progression-free survival approached significance (20.2 vs 9.2 months, p = 0.091). Conclusion In an institution where the culture is to offer clinical trials to all eligible patients, 33% of front-line EOC patients did not participate. Increasing age was associated with non-participation. Modifiable barriers must be overcome so that trial enrollment can better reflect true EOC demographics. [ABSTRACT FROM AUTHOR]

Objective To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I–III trials. Methods An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. Results One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60–70 years and an additional 5% were > 70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p = 0.006). Histology and tumor stage did not significantly differ. Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p = 0.022 and p < 0.001 respectively). Only all grade lymphatic (p = 0.006) and grade ≥ 3 cardiovascular toxicities (p = 0.019) were found to vary with age. A 2% increase in the risk of death for every year increase > 50 for all-cause mortality (HR 1.02; 95% CI, 1.01–1.04) was found, but no association between age and disease specific mortality was found. Conclusion This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were > 60 years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities. [ABSTRACT FROM AUTHOR]

The Precision Medicine Initiative is an NCI driven program in cancer to generate the scientific evidence needed to move the concept of precision medicine into clinical practice. The rapid development and widespread availability of next generation sequencing and other molecular interrogation of tumors has heralded a new era of knowledge about each individual's tumor at a point in time. In some instances, this information has led to new therapeutic discoveries, in most instances, this information has been uninformative or of unclear significance. The NCI Molecular Analysis for Therapy Choice (MATCH) trial [NCT02465060] which screens for molecular features that may predict response to a drug with a given mechanism of action, is a multi-study, collaborative effort between the NCI and many pharmaceutical companies to begin to clarify the significance of molecular alterations in tumors not previously studied. This trial design is in response to the recent appreciation that certain driver mutations which may be common in a particular tumor type are mutated in other diseases at low frequency (b10%). In low frequency mutations, testing the utility of certain targeted therapy requires screening large numbers of patients. This review article will discuss the types of novel trial designs that led to the development and launch of the NCI MATCH. [ABSTRACT FROM AUTHOR]

Objectives Ang1 & 2 (angiopoietin-1; − 2) interact with Tie2 receptors on endothelial cells to mediate vascular remodeling in an angiogenesis signaling pathway distinct from the VEGF axis. Trebananib is a peptide Fc fusion protein that binds Ang1 and 2 and prevents interaction with Tie2. The efficacy of trebananib in recurrent/persistent endometrial cancer (EC) was studied. Methods The primary objective was to determine the frequency of patients with objective tumor responses (ORR) and event-free survival for ≥ 6 months (6-month EFS) and determine toxicity of trebananib at a dose and schedule of 15 mg/kg, IV QW. Recurrent/persistent EC, measurable disease, and ≤ 2 prior chemotherapy lines were required. Results Thirty-two patients were eligible and treated. The most common histologies were G1/2 endometrioid (31%), G3 endometrioid (28%) and serous (31.3%). 78% of patients had 1 prior regimen. Patients received 1–9 + cycles of trebananib; 24 patients (75%) received ≤ 2 cycles. One patient had a partial response (3.1%); 8 patients had stable disease (25%) and 5 patients (15.6%) had 6 month EFS. Median progression-free survival and overall-survival were 1.97 months (90% CI 1.77–2.1) and 6.6 months (90% CI 4.01–14.75), respectively. Most common adverse events (AEs) were fatigue, anemia, and GI issues. Grade 3 and 4 AEs were: GI 31 and 0%; vascular 22 and 0%; metabolism/nutrition 19 and 3%; and general (including edema) 16 and 0%. Conclusions Trebananib has insufficient single agent activity in recurrent EC to warrant further investigation at this dose/schedule. [ABSTRACT FROM AUTHOR]

Abstract: Background: Epithelial growth factor receptor over-expression correlates with poor outcomes in cervical cancer. This study assessed the safety of chemoradiation with cetuximab in the treatment of women with newly diagnosed locally advanced cervical cancer. Methods: Patients received weekly cisplatin 30 and 40mg/m2 [dose level (DL) 1 and 2] and cetuximab 400mg/m2 loading dose and then 250mg/m2 for a total of six weeks with radiotherapy (RT). Patients with nodal metastases received extended field radiation therapy (EFRT). At the maximum tolerated dose, feasibility was evaluated in a 20 patient two-stage, sequential design. Results: In patients receiving pelvic RT, seven were treated at DL 1 with one dose-limiting toxicity (DLT) (febrile neutropenia with grade 3 diarrhea) and three at DL 2 with two DLTs (grade 3 rash and delay in RT >8weeks). The feasibility phase was opened at DL1. Of the 21 patients treated there was one DLT (grade 4 CVA). Median RT duration was 50days (range, 42–70). In patients receiving EFRT, nine were treated at DL 1 with 1 DLT (grade 3 mucositis) and 24 in the feasibility phase with eight DLTs [delay in RT >8weeks due to toxicity (2) and one each with grade 3 or 4 small bowel obstruction, embolism, mucositis, mucositis with hypokalemia, pain with headache, and platelets with mucositis and headache]. Median EFRT duration was 56days (range, 36–74). Conclusions: For patients receiving pelvic RT, cisplatin and cetuximab were feasible. For patients receiving EFRT, combination of cisplatin and cetuximab was not feasible. [Copyright &y& Elsevier]

Abstract: Objective: The cornerstone of therapy for advanced ovarian cancer is cytoreductive surgery (CRS) followed by platinum based chemotherapy. Optimal management for very elderly women (>80) is unclear. This study sought to review the experience with treating ovarian cancer in this population. Materials and methods: This is a retrospective analysis of patients treated between 1991 and 2006. Outcomes included post-operative complications, chemotherapy received and overall survival. Statistical analysis was performed with SAS v.9.1. Results: 85 patients were identified with a mean age of 84 years. 86% of patients presented with advanced disease. Primary CRS was performed on 80%. Among patients with advanced disease who underwent either primary (68) or interval debulking (2), 74% were left with <1 cm residual disease. Post-operative complications were common with 15% of patients suffering cardiac or pulmonary complications, over 10% with prolonged ileus, wound complications or mental status changes and over 30% requiring transfusion or antibiotics. Death prior to hospital discharge and within 60 days of surgery occurred in 13% and 20%. Among patients who underwent CRS, 13% were unable to receive indicated adjuvant therapy. Among those who were treated, 25% were treated with single agent platinum and 43% completed <3 cycles. Two-year overall survival for those who underwent CRS followed by adjuvant therapy is 51%. Conclusions: Our data suggests that patients >80 may not tolerate combination surgery and chemotherapy. The extremely high proportion of post-operative complications and relatively high proportion of post-operative deaths argues for a more prudent approach to this group of patients. [Copyright &y& Elsevier]

Abstract: Objective. : Primary carcinoma of the fallopian tube (PCFT) is a rare malignancy comprising 1% of genital tract cancers. We sought to compare survival trends between PCFT and ovarian carcinoma (OC) patients (pts) in a matched, case–control comparison. Materials and methods. : Patients with PCFT were identified from five academic centers. Two OC controls were identified for each PCFT pt based on age, stage, and residual disease. All pts were surgically staged and treated with platinum based chemotherapy (CT) if indicated. PFS and OS were then compared with Kaplan–Meier analysis. Results. : 96 PCFT cases and 189 OC controls were identified. 50 early stage PCFT were matched with 97 OC pts. The most common CT regimen was carboplatinum and paclitaxel in 84 and 86% respectively. Median follow-up was 57 and 42 months for the PCFT and OC groups and 5-year overall survival (OS) differed at 95% and 76% (p =0.02). 46 Stage III/IV PCFT pts were matched with 92 OC controls. 88.5% were optimally debulked. Median follow-up was 33 and 35 months for PCFT and OC pts and 3-year overall survival was 59% for both groups. Conclusions. : This is the first study to compare outcomes for PCFT and OC in a matched, case–control comparison. Our study demonstrates that, for advanced stage PCFT, a similar survival outcome is obtained compared to OC patients. This should reassure clinicians that treatment of PCFT should mirror that of OC and that PCFT should be included in clinical trials. [Copyright &y& Elsevier]

Abstract: Objective. : We evaluated prognostic, demographic and outcome data for patients >80 years old with uterine cancer (UC). Methods. : A retrospective review of clinical records was performed. Categorical data were compared using Fisher''s exact test and Kaplan-Meier for survival data. Results. : Sixty-five patients were identified with a mean age of 84 and BMI 27. Sixty-five percent of patients had medical co-morbidities. Forty-two (65%) were Stage I; 10 (15%) were Stage II; 8 (12%) were Stage III; and 5 (8%) were Stage IV. Stage I patients included those identified via hysterectomy with lymph nodes (LND) (30) or clinical impression (12). Comparing clinically Stage I UC to those with LND, the clinical group was older (86 vs. 83; p =0.01) and tended to have more medical co-morbidity (89% vs. 63%; p =0.14). Two-year overall survival (OS) among unstaged vs. staged patients was 62% vs. 77%; p =0.11. Among staged patients with Stage I UC, 21 (70%) met high intermediate risk (HIR) criteria per GOG 99 and 90% received no adjuvant therapy. Three patients (16%) recurred with 1 (5%) locoregional recurrence. Two-year OS is 77%. Conclusion. : Elderly patients with UC have features associated with extrauterine spread. Both clinically and surgically staged Stage I patients had excellent OS at 2 years despite no adjuvant therapy. Prevalent medical co-morbidities may impact survival more than recurrence risk. The 23% recurrence rate among HIR patients in GOG 99 was not observed in our data, suggesting that observation for elderly Stage I patients is acceptable. [Copyright &y& Elsevier]

Abstract: Objectives.: To evaluate the rate of vesicovaginal fistula formation and mortality in women with Stage IVA cervical carcinoma. Methods.: Data were abstracted from the clinical records of women diagnosed with Stage IVA cervical cancer at the time of examination under anesthesia, cystoscopy, and proctoscopy (EUA/C/P) at a single institution from 1994 to 2004. Demographic and treatment characteristics were compared using either Fisher''s exact test or Student''s t-test, as appropriate. Survival was calculated using the Kaplan–Meier method. Results.: Twenty-three patients were diagnosed with Stage IVA cervical cancer. All were diagnosed with extension of disease into the bladder; one patient had rectal involvement as well. Concurrent chemotherapy and radiation was used in 60.8%, while 30.4% received radiation alone and 8.7% elected no treatment. Fifty-six percent of the patients were smokers. Eleven patients (47.8%) developed a fistula at a median time of 2.9 months from cancer diagnosis. Fistula formation was significantly increased among smokers as compared to non-smokers (73 vs 27%; p =0.03). Two patients (8.7%) are alive without evidence of disease at a median follow-up of 19 months. The disease-specific survival is 23.1 months. Patients who developed a vesicovaginal fistula had a median survival of 11.2 months after fistula formation. Conclusions.: High rates of vesicovaginal fistula formation can be expected when treating women with extension of cervical cancer into the bladder, particularly among women who smoke. The routine use of EUA/C/P at the time of initial diagnosis aids in counseling women about the likelihood of this complication. Novel strategies for managing vesicovaginal fistulae after chemoradiation are needed. [Copyright &y& Elsevier]

Abstract: Objective. : Cisplatin-based combination therapy produces higher response rates and improved survival, in comparison to single-agent cisplatin in the treatment of cervical cancer. Cisplatin and paclitaxel (PT) requires a prolonged infusion and is less convenient and more toxic than the combination of carboplatin and paclitaxel (CT) leading to more widespread use of CT. The objective of this study was to compare response rate and survival in patients with cervical cancer treated with PT or CT. Methods. : A retrospective search of databases at the University of Oklahoma, Washington University–Barnes Jewish Christian Hospitals, Johns Hopkins University, and University of Alabama at Birmingham identified patients with stage IVB, recurrent or persistent cervical cancer who were treated with PT or CT. Results. : A total of 62 patients were identified. 14 were treated with PT and 48 with CT. There were no statistical differences between the groups in terms of demographics, prior radiation therapy, or median number of cycles. There was a trend toward a larger number of patients in the CT arm having received prior cisplatin/radiation (p =0.07). Objective responses occurred in 29% of patients receiving PT vs. 53% of patients receiving CT. With a median follow-up of 9 months, survival was not different with a median survival of 14 and 11 months, respectively. Conclusions. : In this retrospective evaluation, CT compares favorably with PT and demonstrates a superior overall response rate. Because of its ease of administration and improved toxicity profile, CT should be considered in the treatment of advanced, recurrent or progressive cervical cancer. [Copyright &y& Elsevier]

Early reports of PD-1 inhibition in ovarian clear cell carcinomas (OCCC) demonstrate promising response. We evaluated the combination of pembrolizumab and IDO-1 inhibitor epacadostat in patients with recurrent OCCC. This single arm, two-stage, phase 2 trial included those with measurable disease and 1–3 prior regimens. Patients received intravenous pembrolizumab 200 mg every 3 weeks and oral epacadostat 100 mg twice a day. Primary endpoint was overall response rate (ORR), secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). The study was powered to detect an absolute 25% increase in response (15% to 40%). Between September 28, 2018 and April 10, 2019, 14 patients enrolled at first stage. Rate of accrual was 2.3 patients per month. Median age was 65 years (44–89), 10 (71.4%) had ≥2 prior regimens. ORR was 21% (95% CI 5–51%) within 7 months of study entry with 3 partial responses, and 4 had stable disease (disease control rate 50%). Median PFS was 4.8 months (95% CI: 1.9–9.6), OS 18.9 months (95% CI: 1.9-NR). Most common grade ≥ 3 adverse events were electrolyte abnormalities and gastrointestinal pain, nausea, vomiting, bowel obstruction. In July 2019, the study reached the pre-specified criteria to re-open to second stage; however, the study closed prematurely in February 2021 due to insufficient drug supply. Pembrolizumab and epacadostat demonstrated an ORR of 21% in this small cohort of recurrent OCCC. The rapid rate of accrual highlights the enthusiasm and need for therapeutic studies in patients with OCCC. • Pembrolizumab and epacadostat had an overall response rate of 21% in this cohort of recurrent ovarian clear cell carcinomas. • It is difficult to conclude whether this is an effective combination given the underpowered sample size due to early closure. • Rapid accrual in the first stage surpassed the estimated accrual rate, highlighting the need for trials for this rare tumor. [ABSTRACT FROM AUTHOR]

Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2 -mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non‑platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. Non‑platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3–3.5× times greater than intravenous non‑platinum-based regimens. High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care. • Non‑platinum therapies are more cost-effective in comparison to bevacizumab and PARPi for platinum-resistant ovarian cancer. • Even when adjusting for quality of life, the non‑platinum chemotherapy proved to be the most cost-effective. • Primary expense of novel therapies lies in high developmental costs, rather than costs of infusions and complications. [ABSTRACT FROM AUTHOR]

• The pandemic COVID-19 requires alternative methods and thinking to keep healthcare professionals and patients safe. • In COVID-19 hot spots, oral therapies may be viable alternatives to intravenous therapies for treatment of ovarian cancer. • Minimizing patient visits to hospitals and cancer clinics may help mitigate the spread of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

As precision medicine has become a focus in oncology in recent years, many targeted and biologic agents are being used along with or in place of traditional cytotoxic chemotherapy. As these drugs have been developed and some have received FDA approval, we have gained substantial data about the adverse event profiles. However, the management and approach to the toxicities incurred and subsequent complications are often not well understood, especially for physicians who have a varied clinical practice. The purpose of this review is to provide an overview of the frequency and types of adverse events and appropriate management steps when prescribing modern targeted therapies for gynecologic cancers in the classes of anti-angiogenic agents, poly-ADP-ribose polymerase (PARP) inhibitors, and immunotherapy drugs. [ABSTRACT FROM AUTHOR]

Purpose To characterize folate receptor alpha (FRα) expression in archival and fresh biopsy tumor samples from relapsed ovarian cancer patients. Methods Patients with ovarian tumors amenable to biopsy were eligible to enroll. Eligibility included a minimum requirement of FRα positivity in archival tumor samples (≥ 25% of cells with ≥ 2 + staining intensity). Patients received mirvetuximab soravtansine at 6 mg/kg once every 3 weeks. Core needle biopsies were collected before and after treatment and FRα levels assessed by immunohistochemistry. Descriptive statistics were used to summarize the association between receptor expression and response. Results Twenty-seven heavily pre-treated patients were enrolled. Six individuals (22%) did not have evaluable pre-treatment biopsies due to insufficient tumor cells. The concordance of FRα expression in archival and biopsy tissues was 71%, and no major shifts in receptor expression were seen in matched pre- and post-treatment biopsy samples. Adverse events were generally mild (≤ grade 2) with keratopathy (48%), fatigue (44%), diarrhea, and blurred vision (each 37%) being the most common treatment-related toxicities. The confirmed objective response rate (ORR) was 22%, including two complete responses and four partial responses. Superior efficacy measures were observed in the subset of patients with the highest FRα levels (ORR, 31%; progression-free survival, 5.4 months). Conclusion Concordance of FRα expression in biopsy versus archival tumor samples suggests that archival tissue can reliably identify patients with receptor-positive tumors and is appropriate for patient selection in mirvetuximab soravtansine clinical trials. Regardless of the tissue source analyzed, higher FRα expression was associated with greater antitumor activity. [ABSTRACT FROM AUTHOR]

Evaluate the antitumor activity and safety profile of the combination of mirvetuximab soravtansine and bevacizumab in patients with platinum-resistant ovarian cancer. Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, whose most recent platinum-free interval was ≤6 months, were administered mirvetuximab soravtansine (6 mg/kg adjusted ideal body weight) and bevacizumab (15 mg/kg), intravenously, once every 3 weeks. Eligibility included FRα expression by immunohistochemistry (IHC; ≥25% of cells with ≥2+ intensity). Prior bevacizumab and/or PARP inhibitor (PARPi) treatment were permitted. The primary endpoint was confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety. Ninety-four patients received combination treatment with mirvetuximab soravtansine and bevacizumab. Median age was 62 years (range, 39–81). Fifty-two percent had ≥3 prior therapies; 59% had prior bevacizumab; and 27% had prior PARPi. ORR was 44% (95% CI 33, 54) with 5 complete responses, median DOR 9.7 months (95% CI 6.9, 14.1), and median PFS 8.2 months (95% CI 6.8, 10.0). Treatment-related adverse events were consistent with the profiles of each agent, with the most common being blurred vision (all grades 57%; grade 3, 1%), diarrhea (54%; grade 3, 1%), and nausea (51%; grade 3, 1%). The mirvetuximab soravtansine plus bevacizumab doublet is an active and well-tolerated regimen in patients with FRα-expressing platinum-resistant ovarian cancer. Promising activity was observed for patients regardless of level of FRα expression or prior bevacizumab. These data underscore the potential for mirvetuximab soravtansine as the combination partner of choice for bevacizumab in this setting. • Mirvetuximab soravtansine (MIRV) is a biomarker-driven antibody-drug conjugate targeting folate receptor alpha (FRα). • In platinum-resistant ovarian cancer (PROC), objective response rate was 44% (N = 94; 5 complete and 36 partial responses). • Treatment was efficacious across all FRα expression levels, but further improved with higher FRα expression. • These data support MIRV as a promising and novel combination partner of choice for bevacizumab in patients with PROC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the association of body mass index (BMI) on complications, recurrence, and survival in GOG LAP2, a randomized comparison of laparoscopic versus open staging in clinically early stage uterine cancer (EC). Methods: An ancillary data analysis of GOG LAP2 was performed. Categorical variables were compared using Pearson chi-square test and continuous variables using the Wilcoxon–Mann–Whitney and Kruskal–Wallis tests by BMI group. Survival was estimated using the Kaplan–Meier method. Cox proportional hazards model was used to evaluate independent prognostic factors on survival. Statistical tests were two-tailed with α =0.05, except where noted. Statistical analyses utilized R programming language. Results: 2596 women were included. BMI (kg/m2) groups were <25 (29.5%), 25–30 (28.2%), 30–35 (21%), 35–40 (10.9%), and ≥40 (10.4%). Stage (p =0.021), grade (p <0.001), and histology (p =0.005) differed by BMI. Obese women were less likely to have high risk (HR) disease (+lymph nodes/ovaries/cytology) or tumor features that met GOG99 high intermediate risk (HIR) criteria (p <0.001). Adjuvant therapy (p =0.151) and recurrence (p =0.46) did not vary by BMI. Hospitalization >2days, antibiotic use, wound infection, and venous thrombophlebitis were higher with BMI ≥40. BMI (p =0.016), age (p <0.0001), race (p =0.033), and risk group (p <0.0001) predicted all-cause mortality. BMI was not predictive of disease-specific survival (p =0.79), but age (p =0.032) and risk group (p <0.0001) were significant factors. Conclusion: Obese women have greater surgical risk and lower risk of metastatic disease. BMI is associated with all-cause but not disease-specific mortality, emphasizing the detrimental effect of obesity (independent of EC), which deserves particular attention. [Copyright &y& Elsevier]

In the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (g BRCA) status. Women with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and g BRCA status. 1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n = 586) versus Q3W (n = 546) paclitaxel (ITT: 20.5 vs 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCA wt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between g BRCA m (n = 211) and g BRCA wt (n = 902) subgroups. DD paclitaxel was tolerable and associated with longer PFS in the HR proficient and g BRCA wt groups, versus Q3W. g BRCA status did not impact safety. • Weekly (compared to every 3 weeks) paclitaxel was associated with longer PFS in HRP and BRCA wt cohorts • PFS was improved with veliparib compared with control regardless of paclitaxel dosing schedule • In general, grade 3/4 adverse events were more common in dose-dense paclitaxel groups compared with every-3-week paclitaxel • Germline BRCA status showed no impact on incidences of adverse events across arms [ABSTRACT FROM AUTHOR]

In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy. Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels were measured at baseline and each cycle; radiographic responses were assessed every 9 weeks. Of 1140 patients randomized, 742 had BRCA wild type (BRCA wt) tumors (HRP, n = 373; HRD/ BRCA wt, n = 329). PFS hazard ratios between veliparib-throughout versus control were similar in both BRCA wt populations (HRD/ BRCA wt: 22.9 vs 19.8 months; hazard ratio 0.76; 95% confidence interval [CI] 0.53–1.09; HRP: 15.0 vs 11.5 months; hazard ratio 0.765; 95% CI 0.56–1.04). By Cycle 3, the proportion with ≥90% CA-125 reduction from baseline was higher in those receiving veliparib (pooled arms) versus control (34% vs 23%; P = 0.0004); particularly in BRCA wt and HRP subgroups. Complete response rates among patients with measurable disease after surgery were 24% with veliparib (pooled arms) and 18% with control. These results potentially broaden opportunities for PARPi utilization among patients who would not qualify for frontline PARPi maintenance based on other trials. [Display omitted] • The VELIA trial assessed the PARPi veliparib, combined with frontline chemotherapy and continued as maintenance monotherapy. • Within the BRCA wild type population, survival outcomes were improved regardless of homologous recombination status. • During chemotherapy, radiographic and CA-125 responses were numerically higher with veliparib vs control in all subgroups. • PARPi could benefit a broader patient population than those currently eligible based on prior Phase 3 trials. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : Intraperitoneal (IP) chemotherapy has a clear survival advantage in patients with advanced ovarian cancer, but the high rate of complications has discouraged widespread acceptance. The purpose of this study was to review the completion rate of patients receiving IP chemotherapy as first line treatment at a single institution and determine what factors prohibit completion of therapy. Methods. : Patients receiving IP chemotherapy from 1993 to 2006 were identified by hospital registries for a retrospective review. Charts were abstracted for patient demographics, clinical and pathologic findings, surgical intervention, treatment modalities, and toxicity. Results. : Eighty-three patients were identified who received front line treatment with IP chemotherapy. All patients received a platinum and taxane agent. Port placement (single lumen, venous access device) was completed at time of cytoreductive surgery (33%, n =27) or by mini-laparotomy (67%, n =56). Fifty patients (60%) completed a minimum of 6 cycles of treatment with a mean of 5 cycles. Eleven patients (13%) discontinued treatment due to catheter-related complications including infection (n =4), access difficulties (n =3), grade 4 abdominal pain (n =1), port leaking (n =1), and development of a peritoneal-vaginal fistula (n =1). Sixteen patients (19%) did not complete IP treatment because of chemotherapy-related toxicity. The remaining six patients did not complete chemotherapy due to disease progression or other reasons unrelated to modality of treatment. Conclusions. : Few catheter-related complications were encountered in a review of front-line IP chemotherapy administration at a single institution using a single lumen venous access device. The majority of failures were due to persistent grade 3–4 chemotherapy toxicity. IP chemotherapy can be safely administered by a dedicated health-care team committed to IP chemotherapy as a front-line treatment. [Copyright &y& Elsevier]

GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study (NCT03639246) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D). Eligible patients received AVB-500 at 10, 15, or 20 mg/kg IV q2wk combined with PAC (n = 23) or PLD (n = 30). Patients were treated until progression or unacceptable toxicity. All were followed for survival. No dose limiting toxicities were observed and serum GAS6 was completely suppressed across the three dose levels evaluated. AVB-500 + PAC yielded better clinical activity than AVB-500 + PLD with an ORR of 34.8% (8/23, 2 complete responses) and median DoR, PFS, and OS of 7.0, 3.1, and 10.3 months, respectively. Subgroup analyses showed AVB-500 + PAC patients who had no prior bevacizumab or whose AVB-500 trough levels were >13.8 mg/L exhibited the best clinical response. The ORR and median PFS and OS in patients with these characteristics were ≥50%, ≥7.5 months, and ≥19 months, respectively. Given AVB-500 nor the combination with chemotherapy was expected to cause DLTs, the RP2D of AVB-500 was 15 mg/kg identified using an MIDD approach. AVB-500 was well-tolerated in combination with PAC or PLD and contributed to the clinical activity of PAC in PROC patients. Subgroup analyses identified a population of PROC patients who may benefit the most from AVB-500 treatment, which will be further assessed in an ongoing Phase 3 PROC trial. • The combination of AVB-500 plus chemotherapy was safe and tolerable with no DLTs identified. • At the AVB-500 RP2D (15 mg/kg), AVB-500+PAC demonstrated better clinical activity than AVB-500+PLD. • Patients with no prior bevacizumab had greater clinical response than those with prior bevacizumab and historical control. • An exposure-response relationship was identified for AVB-500 trough levels >13.8 mg/L exhibiting greater clinical response. • A pretreatment serum biomarker may identify patients who benefit from AVB-500 in combination with chemotherapy. [ABSTRACT FROM AUTHOR]

This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer. Eligible patients were 18 years or older with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. Balstilimab was administered intravenously at 3 mg/kg once every two weeks, for up to 24 months. The primary endpoint was objective response rate (ORR, RECIST v1.1) as assessed by an independent review committee. At data cutoff, 161 women (median age, 53 years [range 25–81]) were enrolled and treated with balstilimab. Of these, 140 had measurable disease at baseline and one prior line of platinum-based therapy in the metastatic, persistent, or recurrent setting; these patients were included in the efficacy analyses. The ORR was 15% (95% CI, 10.0%–21.8%) and included 5 patients with a complete response and 16 with a partial response. The median duration of response was 15.4 months. In patients with PD-L1-positive tumors the ORR was 20%, however patients with PD-L1-negative tumors also responded to balstilimab (ORR, 7.9%). Responses were not restricted to tumors of squamous cell histology, and an ORR of 12.5% was seen in the subset of patients with cervical adenocarcinoma. The disease control rate was 49.3% (95% CI, 41.1%–57.5%). Immune-mediated enterocolitis (3.1%) and diarrhea (1.9%) were the most common grade 3 or higher treatment-related adverse events. Balstilimab demonstrated meaningful and durable clinical activity, with manageable safety, in patients with previously-treated, recurrent/metastatic cervical cancer. • Balstilimab elicited promising and durable clinical activity in patients with recurrent/metastatic cervical cancer. • Tumor responses occurred irrespective of tumor PD-L1 status or histology. • Balstilimab is well tolerated, with a safety profile consistent with other PD-1 inhibitors. • These findings highlight balstilimab as an attractive candidate for both single-agent and combination-based immunotherapy. [ABSTRACT FROM AUTHOR]

The GOG Foundation, Inc. (GOG-F) is a non-profit 501(c)(3) organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. GOG Partners (GOG-P) is a program of the GOG-F and is positioned alongside NRG Oncology under the GOG-F organizational umbrella. GOG-P operates outside of the federally funded NCI NRG Oncology, a key distinguishing feature. By functioning as a site management organization (SMO), GOG-P provides an additional platform for clinical trial development, mentorship opportunities, patient accrual, and site infrastructure support yielding an expanded gynecologic oncology clinical trials infrastructure in the US. GOG-P has a consistent track record of conducting high quality clinical trials that lead to bringing novel FDA approved treatments for gynecologic cancer. This manuscript summarizes the history and organizational structure of the GOG-P. In addition, we outline the other key supportive programs within the GOG-F that help support the GOG-P effort to perform transformative gynecologic cancer research. • The GOG Foundation is a nonprofit organization promoting excellence in clinical and basic scientific research. • The GOG Foundation supports clinical trial development, mentorship, patient accrual and site infrastructure support. • GOG Partners is a component of the GOG Foundation and is structured to conduct clinical trials funded by industry sponsors. • GOG Partners expands the US gynecologic oncology clinical trials network via its function as a site management organization. [ABSTRACT FROM AUTHOR]

Increasing measures of adiposity have been correlated with poor oncologic outcomes and a lack of response to anti-angiogenic therapies. Limited data exists on the impact of subcutaneous fat density (SFD) and visceral fat density (VFD) on oncologic outcomes. This ancillary analysis of GOG-218, evaluates whether imaging markers of adiposity were predictive biomarkers for bevacizumab (bev) use in epithelial ovarian cancer (EOC). There were 1249 patients (67%) from GOG-218 with imaging measurements. SFD and VFD were calculated utilizing Hounsfield units (HU). Proportional hazards models were used to assess the association between SFD and VFD with overall survival (OS). Increased SFD and VFD showed an increased HR for death (HR per 1-SD increase 1.12, 95% CI:1.05–1.19 p = 0.0009 and 1.13, 95% CI: 1.05–1.20 p = 0.0006 respectively). In the predictive analysis for response to bev, high VFD showed an increased hazard for death in the placebo group (HR per 1-SD increase 1.22, 95% CI: 1.09–1.37; p = 0.025). However, in the bev group there was no effect seen (HR per 1-SD increase: 1.01, 95% CI: 0.90–1.14) Median OS was 45 vs 47 months in the VFD low groups and 36 vs 42 months in the VFD high groups on placebo versus bev, respectively. High VFD and SFD have a negative prognostic impact on patients with EOC. High VFD appears to be a predictive marker of bev response and patients with high VFD may be more likely to benefit from initial treatment with bev. • Subcutaneous fat density (SFD) and visceral fat density (VFD) appear to be prognostic biomarkers for EOC. • High VFD may also be a predictive biomarker for use of bevacizumab in this patient population. • There was no correlation between IL-6 and VFD as predictive biomarkers for use of bevacizumab. [ABSTRACT FROM AUTHOR]

To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days −2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA- associated tumors. Patients with BRCA- associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA- associated and wild type cancers (HR 0.96, CI 0.65–1.42), though this study's primary aim was not to evaluate outcomes. Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA- associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed. • BRCA status does not affect hematologic AEs experienced by women receiving cytotoxic therapy with bevacizumab and veliparib. • Rates of non-hematologic and hematologic AEs were similar between all 3 regimens. • Rates of hematologic AEs were similar between continuous and intermittent veliparib dosing. • Median progression free survival was not significantly different between BRCA associated and wild type cancers. [ABSTRACT FROM AUTHOR]

Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-cancer gene therapy, in combination with paclitaxel in patients with platinum resistant ovarian cancer (PROC). The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity. The median age of the evaluable patients was 62 years (range 41–82); 97% had high-grade serous cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%. At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified. • OVAL is a Phase III trial using paclitaxel and VB-111 in recurrent ovarian cancer • VB-111 has a dual mechanism targeting tumor vasculature and anti-tumor immunity • CA-125 response in the VB-111 treated arm met the pre-specified interim criterion • Assuming balanced randomization, the response in the VB-111 arm was at least 58% • The OVAL study has been recommended to continue enrollment as planned [ABSTRACT FROM AUTHOR]

• Cemiplimab treatment is efficacious in patients with recurrent or metastatic cervical cancer (cvx ca). • Pembrolizumab with chemotherapy is active and FDA approved in first line treatment of recurrent/metastatic PDL-1 + cvx ca. • Tisotumab Vedotin (TV) received FDA accelerated approval for treatment of recurrent/metastatic cvx ca after chemotherapy. • Transformative advances in cvx ca result from collaborations with GOG-P, ENGOT, other global partners and industry sponsors. • Sequencing includes:1) pembrolizumab with first line chemotherapy 2) TV in second line or pembrolizumab if checkpoint naïve. [ABSTRACT FROM AUTHOR]

To evaluate the safety and preliminary efficacy of demcizumab (DLL4 targeted IgG2 humanized monoclonal antibody; potent inhibitor of the Notch pathway) in combination with weekly paclitaxel in platinum-resistant epithelial ovarian cancer (EOC); and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD). We conducted a 3 + 3 dose-escalation trial in patients with recurrent, platinum-resistant EOC with RECIST v. 1.1 measurable disease and ≤4 prior chemotherapy regimens. Two dosing cohorts (2.5 mg/kg and 5 mg/kg) were targeted; however, an intermediate dose level (3.5 mg/kg) was to be evaluated if the 5 mg/kg dose was not tolerable. Demcizumab was administered on days 1 and 15 and paclitaxel, weekly on days 1, 8, and 15 for each of three 28-day cycles: the 3-cycle doublet could be repeated once if safe. Thereafter, paclitaxel was administered until unacceptable toxicity or disease progression. Nineteen patients were enrolled. No dose-limiting toxicities (DLT) were observed; however, the intermediate dose level (3.5 mg/kg) was enrolled and expanded based on emerging safety data from other trials in the demcizumab program. The MTD was not reached. The most common treatment emergent adverse events (TEAE) were diarrhea (68%), fatigue (58%), peripheral edema (53%), and nausea (53%). Pulmonary hypertension, grade 2 (n = 2) and grade 1 (n = 1), was observed. Overall response rate (ORR) was 21% (95% CI: 6–45%); clinical benefit rate (CBR) was 42% (95% CI: 20–66%). Demcizumab in combination with paclitaxel has a manageable toxicity profile and showed activity in patients with heavily pretreated platinum-resistant ovarian cancer. • The most common demcizumab-related adverse events were fatigue, hypertension, diarrhea, and headache • Grade 1 and 2 pulmonary hypertension were observed • The recommended phase 2 dose of demcizumab in combination with paclitaxel is 3.5mg/kg • Overall response rate was 21% (95% CI: 6-45%); clinical benefit rate was 42% (95% CI: 20-66%) in heavily pretreated women • Of the five patients with prior bevacizumab treatment, two had a partial response and two had stable disease [ABSTRACT FROM AUTHOR]

To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FRα) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FRα-positive, platinum-resistant ovarian cancer. Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were administered mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) and bevacizumab (15 mg/kg) once every 3 weeks. Eligibility included FRα positivity by immunochemistry and prior bevacizumab exposure was permitted. Adverse events, tumor response, and progression-free survival (PFS) were determined. Sixty-six patients, with a median of 3 prior lines of therapy (range, 1–8), received the combination of mirvetuximab soravtansine and bevacizumab at full dosing during the escalation and expansion stages of the study. Adverse events were generally mild-to-moderate (≤grade 2) with diarrhea, blurred vision, nausea, and fatigue being the most common treatment-related toxicities. Six cases of pneumonitis (9%; all grade 1 or 2), an adverse event of special interest, were observed. The confirmed objective response rate (ORR) was 39%, including 5 complete responses and 21 partial responses, and the median PFS was 6.9 months. The combination was particularly active in the subset of patients (n = 16) who were bevacizumab-naïve, less heavily pretreated (1–2 prior lines), and whose tumors exhibited medium/high FRα expression (ORR, 56% with a median duration of response of 12 months; PFS, 9.9 months). The combination of mirvetuximab soravtansine with bevacizumab is well tolerated in patients with platinum-resistant, recurrent ovarian cancer. The encouraging efficacy measures compare favorably to reported outcomes for bevacizumab combined with standard chemotherapy in similar patient populations. • Combining mirvetuximab soravtansine and bevacizumab is a promising approach for platinum-resistant ovarian cancer. • The combination is well tolerated, with a differentiated safety profile compared to bevacizumab with chemotherapy. • The efficacy measures compare favorably to reported outcomes for bevacizumab/chemotherapy in similar patient populations. [ABSTRACT FROM AUTHOR]

This phase 1b/2 clinical trial (NCT01663857) evaluated the efficacy of ralimetinib in combination with gemcitabine (G) and carboplatin (C), followed by maintenance ralimetinib, for patients with recurrent platinum-sensitive epithelial ovarian cancer. Phase 1b was to determine the recommended phase 2 dose (RP2D) of ralimetinib administered Q12H on Days 1–10 (q21d) in combination with G (1000 mg/m2, Days 3 and 10) and C (AUC 4, Day 3) for six cycles. In phase 2, patients were randomized double-blind 1:1 to ralimetinib (R)+GC or placebo (P)+GC, for six cycles, followed by ralimetinib 300 mg Q12H or placebo on Days 1–14, q28d. 118 patients received at least one dose of ralimetinib or placebo; eight in phase 1b and 110 in phase 2 (R+GC, N = 58; P+GC, N = 52). The RP2D for R+GC was 200 mg Q12H. The study met its primary objective of a statistically significant difference in PFS (median: R+GC, 10.3 mo vs. P+GC, 7.9 mo; hazard ratio [HR] = 0.773, P = 0.2464, against a two-sided false positive rate of 0.4). Secondary objectives were not statistically significant for median overall survival (R+GC, 29.2 mo vs. P+GC, 25.1 mo; HR = 0.827, P = 0.4686) or overall response rate (R+GC 46.6% vs. P+GC, 46.2%; P = 0.9667). The safety profile of R+GC therapy was mainly consistent with safety of the chemotherapy backbone alone. Grade 3/4 elevated alanine aminotransferase was more common in the ralimetinib arm. Addition of ralimetinib to GC resulted in a modest improvement in PFS. • This is the first study to combine ralimetinib with gemcitabine and carboplatin. • Modest improvement in PFS was seen with ralimetinib combination and maintenance therapy versus standard-of-care. • The safety profile of ralimetinib combination therapy was mainly consistent with safety of the chemotherapy backbone alone. • Grade 3/4 elevated alanine aminotransferase was more common in the ralimetinib arm. [ABSTRACT FROM AUTHOR]

We sought to determine safety and efficacy of the AKT inhibitor, GSK2141795, combined with the MEK inhibitor, trametinib, in endometrial cancer. Patients with measurable recurrent endometrial cancer were eligible. One to two prior cytotoxic regimens were allowed; prior use of a MEK or PI3K pathway inhibitor was excluded. Initial trial design consisted of a KRAS mutation stratified randomized phase II with a safety lead-in evaluating the combination. For the safety lead in, the previously recommended phase 2 dose (RP2D; trametinib 1.5 mg, GSK2141795 50 mg) was chosen for Dose Level 1 (DL1). Of 26 enrolled patients, 14 were treated on DL1 and 12 were treated on DL-1 (trametinib 1.5 mg, GSK2141795 25 mg). Most common histologies were endometrioid (58%) and serous (27%). Four of 25 (16%) patients were KRAS mutant. Dose limiting toxicities (DLTs) were assessed during cycle 1. DL1 had 8 DLTs (hypertension (n = 2), mucositis (2), rash (2), dehydration, stroke/acute kidney injury). DL1 was deemed non-tolerable so DL-1 was explored. DL-1 had no DLTs. Sixty-five percent of patients had ≥ grade 3 toxicity. There were no responses in DL1 (0%, 90%CI 0–15%) and 1 response in DL-1 (8.3%, 90%CI 0.4–33.9%). Proportion PFS at 6 months for DL1 is 14%, and 25% for DL-1. The combination of trametinib and GSK2141795 had high levels of toxicity in endometrial cancer at the previously RP2D but was tolerable at a reduced dose. Due to insufficient preliminary efficacy at a tolerable dose, the Phase II study was not initiated. • The combination of trametinib (MEK inhibitor) and GSK2141795 (AKT inhibitor) led to high levels of adverse events. • Clinical activity of the combination of trametinib and GSK2141795 was low in patients with recurrent endometrial cancer. • Use of serial biopsies in early phase trials is feasible and may yield information regarding therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Patients with epithelial ovarian cancer (EOC) recurring between 6 and 12 months after primary platinum chemotherapy have worse prognosis than those recurring in >12 months. Artificially prolonging the platinum-free interval (PFI) with cytotoxic chemotherapy was tested in MITO-8 with poor outcomes. This study aimed to determine the impact of using non-platinum or targeted therapy in 2nd line treatment of EOC patients recurring 6–12 months after completion of primary platinum-based chemotherapy. A multi-institutional retrospective review of 177 patients with recurrent EOC and PFI of 6–12 months following primary chemotherapy was performed comparing platinum versus non-platinum chemotherapy or targeted therapy for 2nd line treatment. PFI1 was defined as the date of last chemotherapy to date of recurrence. PFS2/3 were defined as start of 2nd or 3rd line chemotherapy to start of subsequent line. Of 177 patients, the majority of patients were Caucasian, had serous histology, and underwent primary cytoreductive surgery. Median PFI1 was 8.2 months (95% CI 8–9 months). Second line platinum was omitted in 28% of patients. Bevacizumab was used in 2nd line in 16% of patients; 19% received other targeted therapies. Median PFS2 for platinum chemotherapy was longer than non-platinum (7.1 vs 3 months, p = 0.0114). Median PFS2 was significantly longer for platinum vs. targeted therapy (7.1 vs. 3 months p = 0.0431). Median OS for platinum in 2nd line vs. no platinum was 43.6 vs. 37.6 months (p = 0.0174). Use of non-platinum chemotherapy and even targeted therapy to prolong PFI in patients with EOC recurring between 6 and 12 months leads to worse survival. • Non-platinum chemo or targeted therapy to prolong PFI in platinum intermediate recurrent ovarian cancer worsens survival. • This confirms existing prospective data from the MITO-8 study. • Even with targeted therapies, attempts to artificially prolong the PFI are not likely beneficial. [ABSTRACT FROM AUTHOR]

Ovarian cancer has a high mortality to case ratio. To improve the initial response to therapy, trials of biologic agents in combination with primary chemotherapy and as maintenance after completing chemotherapy are being conducted. Multiple trials are ongoing and this strategy has great promise. However, the changing landscape of primary treatment will make designing future trials in ovarian cancer difficult as there may not be a consensus on the optimal primary therapy. We reviewed clinicaltrials.gov for recent and ongoing phase III clinical trials that are likely to impact primary therapy in ovarian cancer. We summarized the objectives and the available data from these trials. A total of 12 potentially practice-changing, randomized phase III trials in front line ovarian cancer were identified in which a biologic therapy was added to primary chemotherapy and/or was used in the maintenance setting. These trials included PARP inhibitors (PARPi), anti-angiogenic agents, immuno-oncology agents, and combinations of these agents. Of the 12 trials, 10 are ongoing, one was terminated for futility, and one has been recently reported. All of these trials emphasize the use of maintenance targeted therapy. In addition, 7 randomized phase III trials utilizing hyperthermic intraperitoneal chemotherapy (HIPEC) were identified in the setting of upfront ovarian cancer treatment. There are multiple ongoing trials in primary ovarian cancer. These trials investigate PARPi, anti-angiogenic agents, immuno-oncology agents, combinations of these agents, and HIPEC. Many of these trials will mature within the next several years and are likely to change the primary treatment of women with ovarian cancer. • There are many trials underway with biologic agents in combination and after primary chemotherapy for ovarian cancer. • SOLO 1 has changed the standard primary therapy for women with BRCA mutated ovarian cancer. • Other trials are likely to change the standard of care for the primary treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Chemo-radiation (chemoRT) has improved the overall survival for locally advanced cervical cancer (LACC) though women whose disease involves the para-aortic nodes (PAN) experience recurrence rates and worse survival outcomes compared to those without PAN involvement. This Phase I study determined if additional cycles of systemic chemotherapy could be safely added to extended field chemoRT in this population of patients. Methods Women with LACC and documented positive PAN were eligible for treatment. All women were treated with extended field radiation and brachytherapy and concurrent cisplatin 40 mg/m2 weekly for six weeks. Four to six weeks after completion of chemoRT, patients were treated with four cycles of paclitaxel 135 mg/m2 and escalating doses of carboplatin (Dose Level (DL) 1 = AUC 4, DL2 = AUC 5). Results Eleven women were entered on study and 9 were evaluable for dose limiting toxicities (DLT). Two women (1 in each of 2 DLs) did not complete chemoRT and so were not evaluable for DLT. Three women completed all 10 cycles at DL 1 with no DLTs. Six women were then treated at DL 2. For the 10 patients evaluable for response, the ORR was 60% (CR + PR). PFS and OS at 12 months were 60% and 90%, respectively. The predominant grade 3 or 4 acute toxicities were hematologic. There were no grade 5 events. Conclusion Extended field chemoRT followed by paclitaxel 135 mg/m2 and carboplatin AUC 5 is feasible in women with LACC and positive PAN. Highlights • Phase I study of sequential extended field ChemoRT and combination chemotherapy • Phase I study for primary therapy of para-aortic node positive cervical cancer • Adjuvant chemotherapy in the primary management of advanced cervical cancer • Safety and feasibility of paclitaxel and carboplatin after extended field RT [ABSTRACT FROM AUTHOR]

Background Performing clinical trials in rare gynecologic cancers presents specific challenges. Strategies for improving accrual and modifications in clinical trial design are outlined. Methods The literature was reviewed in order to present statistical designs pertinent to the study of rare gynecologic cancers. The experience of the Gynecologic Oncology Group/NRG Oncology is outlined as it relates to rare gynecologic cancer clinical trial development. Results Significant progress has been made in studying rare tumors, both nationally and in gynecologic oncology, but challenges inherent to the study of uncommon diseases remain. Important components of these trials include establishing the standard of care, utilizing the appropriate clinical trial design to effectively answer the question in the trial, accurately estimating sample size, choosing modified and realistic endpoints, and avoiding pitfalls specific to rare tumors. Adaptive trial design and statistical modifications are important components of clinical trial design in rare tumors. Conclusion Strategies for effective study of rare gynecologic cancers must be implemented when designing clinical trials for these patients. [ABSTRACT FROM AUTHOR]

The incidence of endometrial cancer (EC) is steadily increasing due in large part to an aging world population and rise in rates of obesity. Patients with obesity and advancing age can be seen as vulnerable populations, as they are both often subject to physician bias regarding surgical choices and assumptions regarding long-term outcomes. As we operate on an older and/or obese patient population, it is increasingly important that we adopt peri-operative management strategies and surgical techniques to best serve this complex patient population. Careful orchestration pre-, intra- and postoperatively is key to successful outcomes in robotic and laparoscopic surgery. Here, we review existing literature regarding EC in women with older age and/or obesity, outline recommendations for peri-operative management and common intra-operative issues—specifically common anesthetic issues surrounding cardiovascular, respiratory and neuromuscular systems—that are of heightened importance in women with older age and/or obesity. The goal of this review is to help define and mitigate common complications for these vulnerable patients with an EC diagnosis who, in accordance with carefully assessed health risks, can and should be offered standard of care surgery and treatment. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to determine the overall tolerability and toxicity of olaparib capsules among older (≥ 65 years) patients with recurrent ovarian cancer treated on 8 completed prospective trials of olaparib. Methods An ancillary data analysis of 398 patients with recurrent ovarian cancer enrolled on eight prospective trials of olaparib capsules was performed. Patients aged 65 years and older were stratified into age groups by 5 year increments (ages 65–69, 70–74, ≥ 75 years) and compared to those < 65. Analysis was restricted to those patients receiving the recommended treatment dose of 400 mg PO b.i.d. Results Of the 398 patients included, 78 were ≥ 65 (age 65–69 n = 38, age 70–74 n = 23, age ≥ 75 n = 17). The majority of elderly patients were Caucasian (n = 2 Asian) and had received ≥ 5 prior lines of chemotherapy. In patients < 65, 46.9% required dose reduction as compared to 44.7% of patients 65–69 years, 47.8% of patients 70–74 years, and 64.7% of patients ≥ 75 years ( p = 0.62). In patients < 65 years 41.2% required dose interruption, as compared to 50%, 43.5%, and 64.7% of patients aged 65–69, 70–74, and ≥ 75, respectively ( p = 0.11). There were no occurrences of myelodysplastic syndrome or acute myeloid leukemia in any of the older cohorts. Toxicities, including grade 3/4 nausea, were similar across age groups. Conclusions Tolerability and toxicity of olaparib capsules is similar between women ≥ 65 years and < 65 years of age treated for advanced recurrent ovarian cancer. Use of olaparib should be considered in this patient population. [ABSTRACT FROM AUTHOR]