bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 3 trial of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer.
Authors: Van Driel Willemien , Sikorska Karolina , Schagen van Leeuwen Jules , Schreuder Henk , Hermans Ralph , de Hingh Ignace , Van Der Velden Jacobus , Arts Henriëtte J.G. , Leon Massuger , Aalbers Arend , Victor J. Verwaal , van der Vijver Koen , Aaronson Neil K , Sonke Gabe S. 
Published: September 2018

5519 Background: Cytoreductive surgery and systemic therapy are essential for newly diagnosed ovarian cancer. We conducted a multicenter phase 3 trial to study whether the addition of intraperitoneal chemotherapy under hyperthermic conditions (HIPEC) to interval cytoreductive surgery would improve outcome among patients receiving neo-adjuvant chemotherapy for stage III epithelial ovarian cancer. Methods: We randomly assigned patients who showed at least stable disease after three cycles of carboplatin (area under the curve 6) and paclitaxel (175 mg/m2) to receive interval cytoreductive surgery with or without HIPEC using cisplatin (100 mg/m2). Randomization was performed per-operatively and eligible patients had no residual mass greater than 2.5 mm. Three additional cycles of carboplatin and paclitaxel were given post-operatively. The primary endpoint was recurrence-free survival. Overall survival, toxicity, and quality-of-life were key secondary endpoints. Results: A total of 245 patients were randomly assigned to one of the two treatment strategies. In an intention-to-treat analysis, interval cytoreductive surgery with HIPEC was associated with longer recurrence-free survival than interval cytoreductive surgery alone (15 vs. 11 months, respectively; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49 to 0.86; P=0.003). At the time of analysis, 49% of patients were alive, with a significant improvement in overall survival favoring HIPEC (48 vs. 34 months; HR, 0.64; 95% CI, 0.45 to 0.91, P=0.01). The number of patients with grade 3-4 adverse events was similar in both treatment arms (28% vs. 24%, p=0.61). Quality-of-life analysis will follow. Conclusions: The addition of HIPEC to interval cytoreductive surgery is well tolerated and improves recurrence free and overall survival in patients with stage III epithelial ovarian cancer. Clinical trial information: NCT00426257.
A randomized phase III trial of cisplatin with or without S-1 in patients with FIGO IVB, recurrent, or persistent cervical cancer: An Asian study.
Authors: Lim Soyi , Ochiai Kazunori , Aoki Yoichi , Aoki Daisuke , Kamiura Shoji , Lin Hao , Fujiwara Yasuhiro , Cha Soon Do , Kim Jae Hoon , Kim Byoung , Hirashima Yasuyuki , Fujiwara Keiichi , Kim Young Tak , Kim Seok-Mo , Chung Hyun Hoon , Chang Ting-Chang , Kamura Toshiharu , Takizawa Ken , Takeuchi Masahiro , Kang Soon-Beom 
Published: September 2018

5527 Background: A combination of S-1, an oral fluoropyrimidine, plus cisplatin has been used for advanced gastric cancer in Asia and EU, and lung cancer in Japan. It also evaluated in advanced or recurrent cervical cancer in a phase II setting. We conducted a randomized phase III trial to compare the efficacy and safety of S-1 plus cisplatin with those of cisplatin alone in recurrent or persistent after treatment and FIGO IVB cervical cancer patients. Methods: Stage IVB, recurrent or persistent cervical cancer patients aged ≥ 20 years, ECOG PS 0–1 and adequate organ function were randomly assigned (1:1) to receive S-1 (80–120 mg daily, according to BSA, day 1–14) plus cisplatin (50 mg/m2 on day 1) (study group) or cisplatin alone (50 mg/m2 on day 1) (control group) every 3 weeks. Treatment was continued until disease progression. In all, 360 patients (at least 296 events) with a hazard ratio (HR) for death of 0.72 were required for a two-sided alpha of 5% and power of 80% under 2 years of recruitment and 1.5 years of follow-up. Stratification factors included recurrence in previously irradiated field, previous platinum-based therapy, and institution. Primary endpoint was OS based on intent-to-treat principle, and secondary endpoints were PFS, overall response rate (ORR), and safety. Results: In all, 375 patients were assigned to the study (n = 189) and control (n = 186) groups. Rate of previous platinum-based therapy was 64%. The median survival time was 21.9 and 19.5 months (95% CI, 18.6–25.8 and 17.0–24.3) with the use of unstratified log-rank test in the study and control groups, respectively (log-rank P = 0.125; HR, 0.84; 95% CI, 0.67–1.05). Significant increases in median PFS (7.3 vs. 4.9 months; log-rank P < 0.001; HR, 0.62) and ORR (43.8 vs. 20.1%, P < 0.001) were observed in the study group. Adverse events (grade≥3) were frequent in the study group (80.9 vs. 41.7%) with neutropenia (52.7%), anemia (34.6%), and leukopenia (32.4%) being the most common events. Conclusions: Compared with cisplatin alone, S-1 plus cisplatin did not significantly improve OS but increased ORR, prolonged PFS, and had tolerable safety of patients with stage IVB, recurrent or persistent cervical cancer. Clinical trial information: NCT00770874.
Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).
Authors: Gourley Charlie , Friedlander Michael , Matulonis Ursula A. , Shirinkin Vadim , Selle Frédéric , Scott Clare L. , Safra Tamar , Fielding Anitra , Rowe Philip , Ledermann Jonathan A. 
Published: September 2018

5533 Background: In Study 19 (NCT00753545), a RCT in 265 pts with PSR SOC, the oral PARP inhibitor olaparib significantly improved progression-free survival (PFS) vs placebo (PBO), with the greatest benefit seen in pts with a BRCA1/2 mutation ( BRCAm); an interim overall survival (OS) analysis suggested an advantage for olaparib-treated pts (DCO: Sep 30, 2015; Ledermann et al, 2016). We report a planned final analysis of the long-term benefit of olaparib in pts with PSR SOC in Study 19. Methods: Pts who had received ≥2 prior regimens of platinum-based chemotherapy and were in response to their most recent regimen received olaparib (400 mg bid; capsules) or PBO until disease progression. Retrospective germline or tumor testing resulted in a known BRCAm status for 254/265 pts (96%). Results: At final DCO (May 9, 2016) median OS follow-up was 78.0 months. A long-term treatment benefit and the final hazard ratio (HR) for OS vs PBO (unadjusted for crossover: 13% of PBO pts – full analysis set [FAS]; 23% of PBO pts – BRCAm subgroup) is shown (Table). Details of BRCAwt pts on treatment for ≥6 years will be presented. No new safety signals or changes in olaparib tolerability profile were seen. Conclusions: The Study 19 final analysis shows that olaparib provides clinically significant, long-term treatment benefit in pts with PSR SOC. A durable benefit was seen in ≥10% of BRCAm and BRCAwt pts, who continued to receive and benefit from olaparib for ≥6 years–unprecedented in the relapsed ovarian cancer setting. Olaparib is well tolerated in this pt population and the analysis suggests olaparib confers an OS benefit in BRCAm pts. Clinical trial information: NCT00753545. [Table: see text]
Long-term benefit of niraparib treatment of recurrent ovarian cancer (OC).
Authors: Matulonis Ursula A. , Herrstedt Jorn , Tinker Anna , Marme Frederik , Redondo Andres , Kalbacher Elsa , Ledermann Jonathan A. , Pikiel Joanna , Christensen Rene dePont , Berek Jonathan S. , Juhler-Nøttrup Trine , Oza Amit M. , Meier Werner , Gil-Martin Marta , Hardy-Bessard Anne-Claire , Monk Bradley J. , Rosenberg Per , Wenham Robert Michael , Hazard Sebastien , Mirza Mansoor Raza ,   For the ENGOT-OV16/NOVA Investigators
Published: September 2018

5534 Background: Current therapies for recurrent OC include chemotherapy (C) or bevacizumab (B) in combination with C followed by continuous B, which showed improved progression-free survival (PFS) compared with C followed by placebo (P) over 3.4 months (GOG-0213) or 4.0 months (OCEANS). Potential impact of B on effectiveness of subsequent therapies has not been described. Niraparib (N) is a highly selective PARP 1/2 inhibitor (PARPi). In preclinical studies, N concentrates in the tumor; N showed significantly longer PFS vs P in patients (pts) with recurrent OC following complete/partial response (CR/PR) to platinum based chemotherapy (Plat) in the randomized, controlled, double-blind phase 3 ENGOT-OV16/NOVA trial. We report the long term effect of treatment with N and its impact on subsequent therapy. Methods: Eligibility for NOVA included recurrent OC, fallopian tube or peritoneal cancer, no prior PARPi use, and completion of ≥2 prior courses of Plat, with a CR or PR following the most recent Plat. Pts were enrolled into g BRCAmut or non-g BRCAmut cohorts based on BRCA mutation test results and randomized 2:1 to receive N 300 mg qd or P until progression of disease or death (PD). Tumors were tested for homologous recombination deficiency (HRD). Estimated probability of PD in each cohort at 12, 18 and 24 months post randomization, representing ~18, 24 and 30 months post chemotherapy initiation, was determined; the difference between PFS2 and PFS (PFS2-PFS) was evaluated in all randomized pts. Results: 203 pts were randomized in the g BRCAmut cohort. Of 350 pts randomized in the non-g BRCAmut cohort, 162 had HRD+ and 134 HRD− tumors. Estimated probability (product-limit method) of PFS at 12, 18 and 24 months was greater in the niraparib arm than in the placebo arm in each cohort and subgroup at each time interval. Probabilities (95% CI) at 24 months for niraparib vs control were 0.42 (0.30, 0.55) vs 0.16 (0.07, 0.28) (gBRCAmut) and 0.27 (0.19, 0.35) vs 0.12 (0.06, 0.21) (non-gBRCAmut). PFS2-PFS was similar in the 2 treatment arms in the combined cohorts (HR 1.02, 95% CI 0.765, 1.349). Conclusions: Niraparib provided long term benefit in pts with recurrent OC irrespective of g BRCAmut or HRD status, and no decrement in the benefit of subsequent therapy was observed. Clinical trial information: NCT01847274.
Management of platinum-sensitive recurrent ovarian cancer (PSROC) in the era of biologics: Can ASCO’s net health benefits (NHB) inform our decisions?
Authors: Foote Jonathan , Havrilesky Laura Jean , Jewell Elizabeth Lin , Gamble Charlotte , Ehrisman Jessie , Broadwater Gloria , Coleman Robert L. , Cohn David E. , Secord Angeles Alvarez 
Published: September 2018

5544 Background: The ASCO value framework allows assessment of novel cancer therapies based on NHB. We assessed novel biologic therapies in the management of PSROC. Methods: ASCO’s revised value framework NHBs were constructed for key therapies based on randomized clinical trials for PSROC. BRCA-germline and HRD status were included. Additionally, patient-centered NHB calculations were weighted based on results from a prospective patient preferences study (n=54) and compared to ASCO-based NHB. Results: ASCO-centered NHB calculations were: platinum + taxane-based chemotherapy (ICON4) = 35; carboplatin + liposomal doxorubicin (CALYPSO) = 22; platinum-based chemotherapy + bevacizumab (OCEANS = 35; GOG 213 = 26). NHB scores based on germline-BRCA alterations were maintenance niraparib (NOVA) = 50 and maintenance olaparib (Study 19) = 62; wild-type BRCA, maintenance niraparib = 36 and maintenance olaparib = 33; and HRD-positive status, maintenance niraparib = 42. Patients valued clinical benefit as the most important component of NHB. Patients valued OS as the most important component of clinical benefit, followed by response rate (RR), then PFS. Patient-weighted NHB were significantly lower than ASCO-weighted scores (mean NHB 37.8 versus 23.5; p=0.009) due to decreased preference for PFS compared to other clinical benefit measures (Table). Conclusions: NHB scores for treatment of PSROC were highest in women with germline-BRCA and HRD tumor alterations who were treated with maintenance PARPi. Our data suggest that a patient-centered NHBs can be used to inform treatment decisions. [Table: see text]
Randomized surgical multicenter trial to evaluate the usefulness of lymphoscintigraphy (LSG) prior to sentinel node biopsy (SLNB) in early breast cancer: SenSzi (GBG80) trial.
Authors: Kummel Sherko , Holtschmidt Johannes , Gerber Bernd , Von der Assen Albert , Heil Joerg , Thill Marc , Krug David , Schem Christian , Denkert Carsten , Lubitz Juliane , Blohmer Jens Uwe , Hötzeld Michael , Seither Fenja , Nekljudova Valentina , Schwidde Ilka , Uhrhan Klara , Von Minckwitz Gunter , Rezai Mahdi , Loibl Sibylle , Kuehn Thorsten 
Published: September 2018

555 Background: It is not clear whether SLNB performed with LSG is necessary to reliably detect sentinel lymph nodes (SLN) in breast cancer. The omission of LSG might offer an accelerated preoperative workflow, cost reduction, and the opportunity for developing innovative, safe detection strategies. Methods: Patients with cN0 early breast cancer or extensive/high grade DCIS received standard radiolabeled colloid LSG and SLNB. Patients were randomized 1:1 to either conducting SLNB with the performing surgeon knowing the preoperative LSG pictures and results or without knowledge of the LSG results. Since the false negative rate (FNR) of SLNB correlates with the number of harvested SLN, our primary endpoint was the average number of histologically detected SLN per patient in both treatment arms in a non-inferiority design. An average number of 2.7 SLN with a standard deviation of 1.8 was assumed. LSG of all patients were collected postoperatively for central review. Results: Between May 2014 and October 2015 n = 1198 patients were randomized in 23 participating breast centers. Baseline characteristics were well-balanced between the treatment arms. Modified intention-to-treat analysis (n = 1163) confirmed the omission of LSG. The average number of histologically detected SLN was 2.207 with LSG and 2.258 without. The range for the one-sided 95% CI for the difference between the arms was (-0.18, +infinity), i.e. above the pre-specified non-inferiority margin of -0.27. Secondary endpoints were analyzed to rule out differences in reliable detection of nodal metastases. Rates of nodal positive disease as identified by SLNB (Odds ratio (OR) 1.005, 95%CI (0.759, 1.33), p = 0.972) and rates of completion axillary dissection (OR 0.984, 95% CI (0.567, 1.71), p = 0.954) in the two treatment arms and in specific subgroups showed no statistically significant differences. Conclusions: Our results support the hypothesis that SLNB is equally effective irrespective of the knowledge of preoperative LSG results. We therefore suggest performing SLNB without LSG to accelerate the preoperative workflow, reduce costs, and improve the comfort for the patients. Clinical trial information: NCT02481128.
Should MMMT of the endometrium/ovary be treated with anthracycline instead of taxane based chemotherapy?
Authors: Heinzelmann-Schwarz Viola A. , Russell Kenneth , Omar Siti , Schoetzau Andreas , Hoeck Kerstin , Vetter Marcus , Fink Daniel A. , Friedlander Michael , Hacker Neville F. 
Published: September 2018

5563 Background: Carcinosarcomas of endometrial (MMMT-E) and ovarian (MMMT-O) origin are rare biphasic tumors, associated with poor prognosis and thought to be epithelial in origin. In view of this, there has been a shift towards carboplatin and paclitaxel rather than anthracycline based chemotherapy regimens which were used when they were treated as “sarcomas”. The purpose of this large retrospective study is to determine whether this change in chemotherapy is associated with better outcomes. Methods: Firstly, clinicopathological features of patients with all stages of MMMT-E (n=103) and -O (n=17) were compared to patients with adenocarcinoma of the endometrium (n=172) and ovary (n=189) in a case-controlled study. Clinicopathological characteristics, FIGO stage, first-line regimens and patient outcomes were analyzed. Secondly, primary tumor specimens of high grade serous ovarian cancers (HGSOC, n=1290) and MMMT-O (n=450) from an independent cohort were analyzed using immunohistochemistry and next generation sequencing to predict response to chemotherapeutic agents. Results: MMMT have a poor prognosis, however, there was a plateau in survival of MMMT-E after 2.5 years in patients with FIGO stage I/II disease, with no recurrence/cancer deaths observed beyond this. There was a statistically significant worse relapse-free survival in patients with MMMT-E treated with carboplatin and paclitaxel compared to carboplatin and anthracyclines (p=0.0011). In the second independent prospective cohort comparing HGSOC versus MMMT-O, both were driven predominantly by p53 mutations. MMMT-O expressed statistically more commonly PI3KCA and KRAS (p=0.015 and 0.018), respectively. Of particular interest, both HGSOC and MMMT-O showed a higher percentage of probability of responding to a combination of carboplatin/anthracyclins (71.2 vs. 73.9%) than carboplatin/taxanes (58.4 vs 39.4%). Conclusions: Patients with MMMT-E and stage I/II have an excellent prognosis if there is no recurrence by 2.5 years. Platinum/anthracyclines regimens appear to be associated with a better outcome than platinum/taxane in MMMT-E and MMMT-O. This could be tested in an international prospective randomized controlled trial.
Predictors of stopping chemotherapy early and short survival in patients with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) who have had ≥3 lines of prior chemotherapy: The GCIG symptom benefit study (SBS).
Authors: Roncolato Felicia , Joly Florence , O'Connell Rachel , Lanceley Anne , Heitz Florian , Buizen Luke , Okamoto Aikou , Aotani Eriko , Salutari Vanda , Donnellan Paul P. , Oza Amit M. , Avall-Lundqvist Elisabeth , Berek Jonathan S. , Hilpert Felix , Feeney Amanda , Roemer-Becuwe Celia , Stockler Martin R. , King Madeleine Trudy , Friedlander Michael ,   GCIG Symptom Benefit Study Group
Published: September 2018

5575 Background: PPS ROC is defined by a platinum free interval > 6 months. Women starting ≥3 lines of chemotherapy for PPS ROC are however a heterogeneous group with variable response to chemotherapy and OS. We sought to identify baseline characteristics (health related quality of life [HRQL] and clinical features) that were associated with stopping chemotherapy early and shorter OS to improve patient selection for palliative chemotherapy. Methods: 378 women with PPS ROC starting ≥3 lines chemotherapy enrolled in GCIG SBS. HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with stopping chemotherapy early (by 8 weeks) were assessed with logistic regression. Associations with OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis (p < 0.05) were included as candidates for multivariable analyses using backward elimination to select those independently significant at p < 0.05. Results: Median age was 64 years. The line of chemotherapy was third in 40%, fourth in 29%, and ≥ fifth in 31%. Chemotherapy was stopped early in 45/378 (12%) and their median OS was 3.4 months. Poor physical function (PF) and global health status (GHS) at baseline were significant univariable predictors of stopping chemotherapy early (p < 0.008); PF remained significant in a multivariable model adjusting for clinical factors (haemoglobin [Hb], ascites, abdominal cramps, neutrophil: lymphocyte≥5, platelets, log CA125); p = 0.03. Median OS in the whole group was 16.6 months. PF, role function, GHS and abdominal/GI symptoms were significant univariable predictors of OS (p < 0.001); PF and GHS remained significant predictors of OS in multivariable models including Hb, ascites, neutrophil: lymphocyte≥5, platelets, log CA125, ECOG and BMI (p < 0.007). Conclusions: In women with PPS ROC ≥3 lines chemotherapy, baseline PF and GHS are independent significant predictors of stopping chemotherapy early and short OS. HRQOL is easily measured, prognostic and may improve clinical trial stratification, patient-doctor communication and support clinical decision making. Clinical trial information: 12607000603415.
Open label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: The Greko II study.
Authors: García-Donas Jesús , Garrigos Laia , Lainez Nuria , Santaballa Ana , Redondo Andres , Cueva Juan Fernando , Rubio M Jesus , Prieto Mario , Lopez-Guerrero Jose Antonio , Garcia-Casado Zaida , Grande Enrique , Guerra Alia Eva , Bover Isabel , Hernando Polo Susana , Sanchez-escribano Ricardo , Hurtado Alicia , Navarro Paloma , Rodriguez-Moreno Juan Francisco ,   GETHI (Spanish Group for Orphan and Unfrequent Tumors)
Published: September 2018

5577 Background: Granulosa-cell tumors (GCT) of the ovary are a rare entity characterized by presenting a punctual mutation at the FOXL2 gene 402C→G (C134W). Such mutation leads to a disregulation and overstimulation of the steroidogenic pathway and, ultimately, hormone overproduction. A prior trial by our group (GREKO I trial-GETHI 2011-03; NCT01584297) showed promising activity of ketoconazole, a CYP17 inhibitor used to control steroidogenesis in several conditions. Thus, we aimed to assess the activity of Orteronel (TAK700), a selective inhibitor of 17, 20-lyase, in GCT. Methods: An open-label phase II single arm clinical trial was designed for women with metastatic or locally advanced non-resectable GCT who harbored the somatic mutation FOXL2 402C→G (C134W) and who had not received prior treatment with any CYP17 inhibitor. Treatment consisted on Orteronel 300mg BID, given orally, continuously in a 28-day treatment cycle. The primary objective was clinical benefit rate; secondary objectives were response rate, progression free and overall survival, assessment of the impact of Orteronel in reducing hormonal overproduction and toxicity. Sample size calculation was based on a two stage Simon´s design. A power of 80% was set to differentiate between a 5% and a 25% clinical benefit rate. 20% of losses had been assumed thus 20 patients were scheduled to be enrolled. Results: Since 30/06/2014 to 11/01/2017 10 patients have been included in 9 participating institutions members of Spanish Group for Research in Orphan and Unfrequent Tumors (GETHI). Due to a low recrutiment rate the study was terminated early. Median PFS was 3 months 95%CI (0-12) with 3 patients achieving disease stabilization longer than 12 months. 2 patients remain on treatment after 16 and 14 months. Clinical benefit rate (CR + PR + SD) was 50%, 95%CI (19%-81%). Seven patients have progressed and 2 have died. Only 6 suspected unresected adverse reactions (SUSARs) have been communicated so far (chest pain, fever, febrile neutropenia, eosinophila, neutropenia and anemia). Conclusions: Orteronel achieved a significant clinical benefit in advanced GCT with an favorable toxicity profile. Clinical trial information: NCT02101684.