bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOLLO: A phase I study of adaptive memory natural killer (NK) cells in recurrent ovarian cancer.
Authors: Geller Melissa Ann , Cooley Sarah A. , Wallet Mark , Valamehr Bahram , Teoh Deanna Gek Koon , DeFor Todd E. , Felices Martin , Miller Jeffrey 
Published: May 2020

6044 Background: Human cytomegalovirus (CMV) infection induces a subset of long-lived CD57+NKG2C+ adaptive NK cells that exhibit enhanced antibody-dependent cellular cytotoxicity and resistance to tumor-suppressive mechanisms. We developed a 7-day culture process using a GSK3 inhibitor and IL-15 to manufacture modulated adaptive NK cells (FATE-NK100) from CMV+ haploidentical donors for adoptive transfer. The phase I Apollo trial tests the maximum tolerated dose/maximum feasible dose (MTD/MFD) of FATE-NK100 administered intraperitoneally (IP) to treat platinum-sensitive or -resistant recurrent ovarian, fallopian tube, and primary peritoneal cancer. Methods: FATE-NK100 via IP port was tested using 3 dose cohorts ([DC]; 1 × 107 cells/kg; >1 × 107 cells/kg to ≤3 × 107 cells/kg; or >3 × 107 to ≤10 × 107 cells/kg) after lympho-conditioning with fludarabine 25 mg/m2 IV and cyclophosphamide 300 mg/m2 IV on days −6 and −5. After FATE-NK100 infusion on day 0, rhIL-2 at 6 million IU was given IP 3 times a week for 6 doses for in vivo NK activation. IP fluid and peripheral blood were collected regularly until response assessment (day 28). Patients with stable disease or better were eligible for retreatment. Pre- and post-treatment tumor biopsies were collected. Results: Nine patients were treated with no dose-limiting toxicities (DLTs) to date. Retreatment based on clinical benefit was performed on 3 patients (33%), 2 following stable disease (DC 2) and 1 with partial remission (48% tumor reduction, DC 3). IP samples were collected for PK and functional analysis. FATE-NK100 product was detected by flow cytometry in 5 of 6 patients with evaluable samples (range 4.8%–91.2% donor NK cells at day +5-7). Retreatment samples were available in 1 patient, where FATE-NK100 persisted to day +21, demonstrating that repeated IP dosing did not accelerate clearance of the donor NK cells. In that same patient, measurement of NK cell CD107a degranulation or IFNg production in response to K562 targets demonstrated sustained enhanced in vivo function of FATE-NK100 compared to endogenous patient NK cells (e.g. at Day +12 CD107a+ NK were 39.0% vs. 22.5% cycle 1, and 40.3% vs. 18.2% retreatment cycle 2, and IFNg+ NK were 12.3% vs. 5.9% cycle 1, and 2.4% vs. 0.2% retreatment cycle 2). Conclusions: IP delivery of FATE-NK100 is safe, with clinical benefit in 3/9 patients treated. The allogeneic product cells persist and have enhanced function compared to patient NK cells for up to 21 days, even after retreatment. This phase I study in recurrent/refractory ovarian cancer shows promise for IP NK cell delivery. Clinical trial information: NCT00652899.
Long-term survival outcomes of intravenous versus intraperitoneal chemotherapy in the treatment of advanced ovarian cancer.
Authors: Kim Rachel Soyoun , Maganti Manjula , Bernardini Marcus , Laframboise Stephane , Ferguson Sarah E. , May Taymaa 
Published: May 2020

6046 Background: The role of intraperitoneal (IP) chemotherapy in the management of advanced ovarian cancer has been questioned given emerging evidence showing lack of survival benefits. The objective of this study was to compare the long-term survival associated with IP chemotherapy at a tertiary cancer center. Methods: We reviewed the long-term survival records of 271 women with stage IIIC or IV high-grade serous ovarian cancer treated with primary cytoreductive surgery (PCS) followed by IP or intravenous (IV) chemotherapy between 2001-2015 with a minimum follow-up of 4 years. 5-year progression free (PFS) and overall survival (OS) rates were compared using Kaplan-Meier survival analysis and covariates were evaluated using Cox regression analysis. Results: Women who received IP chemotherapy after PCS (n = 91) were more likely to have undergone aggressive surgery (p < 0.001), longer surgery (p < 0.001), and had no residual disease (p < 0.001) compared to the IV arm (n = 180). Median follow-up was 51.6 months. Five-year PFS was 19% vs. 18% (p = 0.63) and OS was 73% vs. 44% (p = 0.00016) in the IP vs. IV arms, respectively. After controlling for covariates in a multivariable model, the use of IP was no longer a significant predictor of OS in the entire cohort (p = 0.12). In patients with 0mm residual disease, PFS was 28% vs. 26% (p = 0.67) and OS was 81% vs. 60% (p = 0.059) in IP (n = 61) vs. IV (n = 69), respectively. In patients with residual of 1-9mm, PFS was 30% vs. 48% (p = 0.076) and OS was 60% vs. 43% (p = 0.74) in IP (n = 29) vs. IV (n = 31), respectively. Conclusions: IP chemotherapy showed a trend towards improved survival over conventional IV chemotherapy, especially in patients with no residual disease. Given the retrospective nature and small numbers in this study, prospective non-randomized cohort studies are warranted to evaluate the role of IP chemotherapy in advanced ovarian cancer.
Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION interim analysis.
Authors: Poveda Andres , Lheureux Stephanie , Colombo Nicoletta , Cibula David , Lindemann Kristina , Weberpals Johanne I , Bjurberg Maria , Oaknin Ana , Sikorska Magdalena , Gonzalez Martin Antonio , Madry Radoslaw , Rubio Pérez Maria Jesus , Davidson Richard , Blakeley Christopher , Bennett James , Barnicle Alan , Skof Erik 
Published: May 2020

6057 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al. Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including those in the non-BRCAm subgroup. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al. Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 previous lines of platinum-based chemotherapy, we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and had responded to platinum-based chemotherapy. Pts initiated maintenance olaparib tablets (300 mg bid) until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed PFS (modified RECIST 1.1). Secondary endpoints included PFS by homologous recombination repair deficiency (HRD; assessed with the Myriad myChoice HRD plus test; HRD+ve: score ≥42) and somatic BRCA mutation (sBRCAm) status. An interim analysis was planned after ~135 PFS events. Results: 279 pts were enrolled from 17 countries (mean age: 64 yrs); 94.3% were confirmed non-gBRCAm by local testing. At data cut-off (Nov 15, 2019), the median PFS was 9.2 months (95% confidence interval [CI]: 7.6–10.9 months), with 152 PFS events (54.5% maturity). The Table presents PFS outcomes by key subgroups. The median exposure to olaparib was 8.1 months. Grade ≥3 adverse events (AEs) occurred in 72 (26%) pts. 19% of pts reported serious AEs. No deaths related to AEs were reported. AEs led to dose interruption, dose reduction and treatment discontinuation in 39%, 15% and 7% of pts, respectively. Conclusions: Maintenance olaparib demonstrated activity in non-gBRCAm PSR OC pts. There were no new safety signals. Clinical trial information: NCT03402841. [Table: see text]
Are symptoms distinguishable in ovarian cancer? A nested case control study of insurance claims.
Authors: Langabeer Denise Manon , Krause Trudy , Ganduglia Cazaban Cecilia M , Swartz Michael D , Lopez David S , Bodurka Diane C. 
Published: May 2020

6063 Background: Over 60% of ovarian cancer cases are diagnosed with Stage III and IV disease. The US healthcare system does not support a standard screening method for ovarian cancer. Our goal was to determine whether certain symptoms based on ICD-9 categories are distinguishable among women diagnosed with ovarian cancer and women without ovarian cancer. Methods: Women diagnosed with ovarian cancer were randomly matched 1:1 to women without cancer to support a nested case-control analysis of health insurance claims between 2008 through 2013 from a commercial payer. The following eligibility criteria were applied: 1) 24 years of age or older; 2) continuously enrolled in healthcare plan for a minimum period of 6 months; 3) experienced more than 1 symptom over the observation period; and 4) an observation period of a minimum of 6 months. Symptoms were based on 47 ICD-9 diagnosis codes and categorized specific to pain, abdominal and pelvic, digestive, and bladder. The analysis was based on 1,578 women (789 cases; 789 controls). Results: Overall, 90% (n = 1,421) of the women experienced abdominal and pelvic symptoms, and 92% (n = 725) of the women with ovarian cancer visited their physician for this complaint 6-70 months prior to diagnosis, OR 1.66 (CI 1.14 to 2.41; p = .008). Pain was reported as a complaint by cases at nearly 60% (n = 464) and controls at 48% (n = 376); OR 1.75 (CI 1.39 to 2.19; p < .001). Symptoms for bladder and digestive combined represented 68% of complaints for both cases (n = 507) and controls (n = 555), p = .024 and p = .298, respectively. Of the 1,578 women, 77% (cases = 621; controls = 595) experienced more than one category of symptoms. Both cases (n = 206) and controls (n = 153) complained of abdomen and pelvic symptoms along with pain; OR 1.54 (CI 1.19 to 1.99; p = .001). A second combination included abdomen and pelvic symptoms with pain and digestive symptoms in 14% of women (cases n = 99; controls n = 67); OR 1.58 (CI 1.13 to 2.22; p = .008). Sixty percent (n = 473) of women with ovarian cancer experienced the majority of associated pre-diagnosed symptoms analyzed for the study. Conclusions: Certain recurring symptoms associated with abdomen and pelvic as well as pain appear to indicate an association with ovarian cancer, signifying that symptom awareness remains relevant to this disease that is diagnosed at a late stage and currently does not have routine screening methods to support early detection.
Risk of venous thromboembolism in patients receiving neoadjuvant chemotherapy for ovarian cancer.
Authors: Basaran Derman , Suhner Jessa , Sassine Dib , Boerner Thomas , Liu Ying L , Grisham Rachel N. , Tew William P. , Gardner Ginger J. , Zivanovic Oliver , Sonoda Yukio , Long-Roche Kara C. , Chi Dennis , Soff Gerald A. , Jewell Elizabeth Lin 
Published: May 2020

6073 Background: To identify the incidence of newly occurring venous thromboembolism (VTE) in patients with ovarian cancer receiving neoadjuvant chemotherapy (NACT). Methods: Using our prospectively maintained ovarian cancer database, we identified all ovarian cancer patients who received NACT at our institution from 4/15-9/18. VTE events included clinically diagnosed deep venous thrombosis (DVT) or pulmonary embolism (PE). Patients who presented with VTE prior to induction of NACT or patients on anticoagulation therapy prior to diagnosis were excluded. The incidence of newly occurring thrombotic events were categorized according to treatment phases, defined as 1) NACT prior to interval debulking surgery (IDS); 2) intraoperative and 30-day post-IDS; and 3) adjuvant chemotherapy. Results: 290 patients underwent NACT during the study period. Thirty-eight patients (13%) who presented with VTE, 12 (4%) on anticoagulation at presentation, and 4 (1.4%) seeking only a second opinion were excluded from analysis. Of the 236 evaluable patients, the overall rate of VTE during all treatment phases was 15% (35/236). In treatment phase I, 11% (27/236) of patients experienced VTE during NACT. In phase II, an additional 2.5% (6/236) developed VTE in the intraoperative and 30-day postoperative period. In phase III, an additional 0.8% (2/236) experienced a thrombotic event >30 days postoperatively. Sevety-seven percent (27/35) of VTE events occured during phase I. Conclusions: Patients receiving NACT for advanced ovarian cancer are at high risk for the development of clinically detectable thromboembolic events. The highest rate of new VTE events was seen during induction of NACT, a phase of treatment traditionally without any prophylactic anticoagulation. Further research regarding the timing of thromboprophylaxis for this patient population is warranted. [Table: see text]
Influence of BRCA pathogenic variants in the benefit of secondary cytoreductive surgery.
Authors: Estati Felipe Leonardo , Alencar Viviane , Pirolli Rafaela , Ribeiro Adriana Regina Goncalves , Torrezan Giovana Tardin , Carraro Dirce Maria , Formiga Maria Nirvana , Guimaraes Andrea Paiva , Baiocchi Glauco , Da Costa Alexandre Andre B. A. 
Published: May 2020

6076 Background: Germline BRCA pathogenic variants are present in 15% to 25% of ovarian carcinoma patients. These tumors are more sensitive to platinum and PARP inhibitor therapy and have a better prognosis. Two retrospective studies with limited number of patients have shown conflicting results regarding the benefit of secondary cytoreductive surgery (SCS) in patients with BRCA mutations. Our aim was to evaluate the impact of SCS in recurrent ovarian cancer according to BRCA status. Methods: All patients with ovarian carcinoma with recurrent disease and who were tested for BRCA pathogenic variants treated at a tertiary Cancer Center in Brazil were included. Patients characteristics were compared between patients treated with SCS and not treated with SCS. Cox regression analysis was used to evaluate the impact of SCS on progression free survival (PFS) and the influence of BRCA pathogenic variants on the effect of SCS. Results: One hundred and forty patients were included, 49.6% were treated with SCS and chemotherapy and 50.4% treated with chemotherapy only. Patients treated with SCS were younger, presented better performance status, lower CA 125 and longer platinum free interval. After adjusting for relevant covariables SCS was associated with longer PFS (HR 0.53, 95%CI 0.29-0.97, p = 0.039). Germline BRCA pathogenic variants were found in 37 patients (26.4%). No patient was treated with PARP inhibitors. Among non-carriers of pathogenic variants in BRCA, SCS lead to a longer PFS (HR 0.48, 95%CI 0.28-0.81, p = 0.006) but among carriers there was no benefit of SCS (HR 0.84, 95%CI 0.30-2.34, p = 0.735). Test for interaction was not statistically significant (p = 0.359). Conclusions: Our study is the second to demonstrate no benefit of SCS among patients with BRCA pathogenic variants and not treated with PARP inhibitor. The only other study to show a benefit of SCS in this group of patients included a limited number of patients and all of them were treated with PARP inhibitors. BRCA germline status might influence the efficacy of SCS, and should be evaluated as a potential biomarker to be assessed together with clinical factors to better select patients for SCS.
An open-label, multicenter, phase Ib/II study of rebastinib in combination with paclitaxel in a dose-expansion cohort to assess safety and preliminary efficacy in patients with advanced or metastatic endometrial cancer.
Authors: Janku Filip , Hamilton Erika Paige , Chu Christina , Richardson Debra L. , Arend Rebecca Christian , Kuida Keisuke , Achour Haroun , Ruiz-Soto Rodrigo , Hays John L. 
Published: May 2020

6085 Background: Rebastinib is a switch control inhibitor targeting tunica interna endothelial cell kinase (TIE2). TIE2 is primarily expressed in endothelial cells playing a role in angiogenesis. TIE2 is also expressed in a subset of macrophages with pro-metastatic and immunosuppressive properties and linked to chemo-resistance. This study is a 2-part open-label, phase Ib/II, multicenter study of rebastinib orally administered, in combination with paclitaxel. In Part 1, we observed encouraging antitumor activity of rebastinib with 5 PRs in 24 patients (pts) at 50 mg BID and 3 PRs in 19 pts at 100 mg BID from a heavily pretreated heterogeneous patient population. Here we summarize preliminary results from the endometrial cancer (EC) cohort of Part 2. Methods: Part 2 of this study has four disease-specific cohorts (TNBC, inflammatory breast cancer, ovarian cancer and EC). Pts were evaluated for safety (CTCAE v5.0) and efficacy (RECIST v1.1). According to the Simon 2-stage design of this study, for each cohort, 15 additional pts will be enrolled if more than 4 PRs are observed. Results: As of Jan 21, 2020, 19 EC pts were enrolled with a median age of 66 years. All pts received at least one prior line of paclitaxel and 12 (63%) pts received >3 prior anti-cancer therapies. Sixteen pts were treated with rebastinib starting dose 100 mg BID (reduced to 50 mg BID due to a higher frequency of muscular weakness) and 3 pts with 50 mg BID, in combination with 80 mg/m2 weekly paclitaxel with a median duration of treatment 85 days (6, 225). In 15 evaluable pts, there were 5 PRs (4 confirmed) and 6 SD8 weeks for an ORR of 33% and clinical benefit rate of 73%. Treatment-emergent AEs (>20%) were mostly ≤ grade 2: constipation, fatigue (each n=9); alopecia, peripheral edema (each n=8); dysgeusia, peripheral sensory neuropathy, arthralgia (each n=6); diarrhea, hypomagnesaemia, vomiting, dry mouth (each n=5); anemia, decreased appetite, dyspnea, nausea, and muscular weakness (each n=4). Serious AEs possibly related or related to rebastinib included muscular weakness (n=2, at 100 mg BID), head discomfort (n=1) and increase troponin (n=1) which resolved after dose interruption. Conclusions: Preliminary activity of rebastinib in combination with paclitaxel was encouraging in heavily pretreated EC pts, all of whom received prior paclitaxel. The safety profile of rebastinib at 50 mg BID was generally well tolerated. The EC cohort is enrolling at 50 mg BID in stage 2 of the study. Clinical trial information: NCT03601897.
Efficacy and safety of laterally extended endopelvic resection for the pelvic side wall gynecologic tumors: A four-year prospective cohort study with historical comparison.
Authors: Paik Haerin , Park Soo Jin , Kim Hee Seung , Kim Jae-Weon 
Published: May 2020

6092 Background: Although laterally extended endopelvic resection (LEER) has been introduced to control the pelvic sidewall tumors, there is a lack of evidence about its efficacy and safety despite high skillful procedure, compared with the other treatments. Thus, we performed a prospective cohort study with historical comparison for four years. Methods: One gynecologic oncologist performed LEER consecutively for patients with the pelvic sidewall tumors between March 2014 and July 2018. We compared clinicopathologic characteristics and survival between patients who received primary LEER and with those treated with other treatments. Results: We enrolled 37 patients treated with LEER. Among them, 22 (59.5%) and 15 (40.5%) had recurrent and primary disease. Among perioperative outcomes, there was more estimated blood loss, and hospitalization was longer in recurrent disease and previous surgery (p < 0.05). In recurrent disease, previous progression-free survival < 8 months was related to poor recurrence-free survival after LEER (median, 5.4 vs. 10.2 months; p < 0.05). When LEER was applied for the first recurrence of cervical cancer, recurrence-free survival and overall survival after treatment seemed to be longer in LEER (n = 9) than in palliative chemotherapy (n = 27) without statistical significance (median, 12.2 vs. 4.7 months and 23.2 vs. 12.4 months; p = 0.13 and p = 0.63). In 15 patients with primary locally advanced cervical cancer, LEER after partial response to neoadjuvant chemotherapy showed longer progression-free survival than LEER after stable or progressive disease to neoadjuvant chemotherapy and primary radiotherapy (p = 0.012). After LEER, grade 3 and 4 complications developed in 15 (23.1%) and 2 (3.1%) patients. Conclusions: Compared with palliative chemotherapy, LEER followed by palliative chemotherapy may improve progression-free survival in patients with recurrent cervical cancer located in the pelvic sidewall. If possible, it is more effective to apply LEER without preceding palliative chemotherapy for recurrent cervical cancer located in the pelvic sidewall.
GEM20110714: Final overall survival results of the phase III study of first-line gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma.
Authors: Hong Shaodong , Huang Yan , Yang Yunpeng , Yu Gengsheng , Jia Jun , Peng Jiewen , Lin Qing , Xi Xuping , Peng Peijian , Chen Dongping , Xu Mingjun , Lu Xiaojun , Zhang Li 
Published: May 2020

6521 Background: GEM20110714, the first randomized, phase III study (NCT01528618) of systemic chemotherapy in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC), reported significant reduction of disease progression with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio [HR], 0.55; 95% CI, 0·44–0·68; P < .001). This study establishes GP as the standard-of-care for first-line treatment of R/M NPC. We present the final overall survival (OS) analysis here. Methods: In this multicenter, open-label study conducted in China, patients who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and R/M NPC were randomly assigned (1:1) to receive up to six cycles of either GP or FP once every 3 weeks. The primary endpoint was PFS, which has been previously reported; OS was a secondary endpoint. The final OS analysis was conducted with the data cutoff date of December 17, 2019. Results: After a median follow-up time of 64.4 months (95% CI, 61.1-67.6), 148 (81.8%) and 165 (91.2%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.723 (95% CI, 0.578 to 0.904; two-sided P = .004). The median OS was 22.1 months with GP versus 18.6 months with FP. The OS probabilities at 1, 3, and 5 years were 79.9% vs. 71.8%, 31.0% vs. 20.4%, and 18.5% vs. 7.6%, respectively. Un-predefined subgroup analyses based on baseline characteristics were consistent with the primary OS analysis. Postdiscontinuation systemic therapy use was similar: GP, 52%; FP, 57%. No new safety signals emerged. Conclusions: In patients with R/M NPC, GP is the first regimen to show significant improvement in OS in a phase III randomized study compared with a traditional chemotherapy regimen (i.e. FP). GP should be considered the standard treatment option for these patients. Clinical trial information: NCT01528618 .