bluuebunny/crossref_metadata_2025_split huggingface dataset:
HERO phase III trial: Results comparing relugolix, an oral GnRH receptor antagonist, versus leuprolide acetate for advanced prostate cancer.
Authors: Shore Neal D. , George Daniel J. , Saad Fred , Cookson Michael , Saltzstein Daniel R. , Tutrone Ronald F. , Akaza Hideyuki , Bossi Alberto , van Veenhuyzen David , Selby Bryan , Fan Xiaolin , Kang Vicky , Walling Jacqueline M. , Tombal Bertrand F. ,   Test Abstract Group
Published: May 2020

5602 Background: LHRH agonists are the mainstay for medical castration in advanced prostate cancer; however, they cause an initial testosterone (T) surge with a delayed onset of castration and require depot injection. Relugolix is the first oral GnRH receptor antagonist, which was previously shown to rapidly suppress T levels. The HERO trial compared the safety and efficacy of relugolix with leuprolide acetate in advanced prostate cancer patients. Methods: HERO is a 48-week, global, pivotal phase III trial that randomized 934 patients with androgen-sensitive advanced prostate cancer in a 2:1 ratio to receive relugolix 120 mg orally QD after a single l or leuprolide acetate 3-month depot injection. The primary endpoint was to achieve and maintain serum T suppression to castrate levels (< 50 ng/dL) through 48 weeks. Key secondary endpoints included castration rates at Day 4, profound castration (< 20 ng/dL) rates at Days 4 and 15, PSA response rate at Day 15 and FSH levels at Week 25. Testosterone recovery was evaluated in a subset of 184 patients. Results: A total of 96.7% (95% CI: 94.9%, 97.9%) of men on relugolix achieved and maintained castration through 48 weeks compared to 88.8% on leuprolide. The difference of 7.9% (95% CI: 4.1%, 11.8%) demonstrated non-inferiority (margin -10%) and superiority (P < 0.0001) of relugolix to leuprolide. All key secondary efficacy endpoints tested demonstrated superiority over leuprolide (P < 0.0001) (Table). In the testosterone recovery subset, median T levels were 270.76 ng/dL in the relugolix compared to 12.26 ng/dL in the leuprolide group 90 days after discontinuation of therapy. In a prespecified analysis, the incidence of major adverse cardiovascular events (MACE) was lower in the relugolix group than in the leuprolide group (2.9% vs. 6.2%, respectively); otherwise the safety and tolerability profiles were generally similar. Conclusion: Relugolix achieved castration as early as Day 4 and demonstrated superiority over leuprolide in sustained T suppression through 48 weeks, faster T recovery after discontinuation and a 50% reduction in MACE. Relugolix has the potential to become a new standard for T suppression for patients with advanced prostate cancer. Clinical trial information: NCT03085095 . [Table: see text]
Radioparp: A phase I of olaparib with radiation therapy (RT) in patients with inflammatory, locoregionally advanced or metastatic triple-negative breast cancer (TNBC) or patient with operated TNBC with residual disease—Preliminary results.
Authors: Kirova Youlia M. , Loirat Delphine , Berger Frederique , Rodrigues Manuel , Bazire Louis , Pierga Jean-Yves , Ricci Francesco , Cao Kim , Vincent -Salomon Anne , Laki Fatima , Ezzili Cyrine , Raizonville Laurence , Mosseri Veronique , Neffati Souhir , Ezzalfani Mounia , Fourquet Alain 
Published: May 2020

571 Background: Preclinical studies have shown that cell lines and murine models of TNBC phenotype are more sensitive to PARP1 inhibitors. This evidence provides strong rationale for developing a new therapeutic approach to TNBC based on targeting the DNA-repair defects via PARP inhibition. Methods: The purpose of this study was to report the Maximal Tolerated Dose (MTD) of Olaparib (O) administered concurrently with locoregional RT and evaluate the Dose-Limiting Toxicity (DLT). Results: Twenty-four pts with performance status 0-1 were enrolled between 09/2017 and 11/2019. Of them, 21 underwent adjuvant RT-O because poor response to NAC, and 3 received preoperative RT+O because of progression after NAC. The patients’ profile is given in table. All patients received full course RT-O, as following: 4 pts at dose 50mg bid; 8 at 100x2; 7 at 150x2, and 5 at 200x2. No DLT was observed. Two pts (8.7%) experienced acute grade 3 dermatitis no grade 4 toxicities related to the RT were observed. The O-related toxicity was acceptable with mostly grade 1-2 symptoms. The only grade 3-4 hematological toxicity was lymphopenia in 11 cases. Conclusions: Dose of O was escalated to the target dose of 200 mgx2, without DLT. Further follow up is needed to evaluate the late toxicities. Clinical trial information: NCT03109080 . [Table: see text]
Neoadjuvant chemotherapy (NACT) and HER2 double inhibition including biosimilar trastuzumab (ONTRUZANT) for HER2-positive early breast cancer (EBC): Population-based real world data from the Danish Breast Cancer Group (DBCG).
Authors: Andersson Michael , Jensen Maj-Britt 
Published: May 2020

577 Background: Increasingly, HER2-positive early breast cancer (EBC) is treated by NACT combined with trastuzumab and pertuzumab followed by surgery. Ontruzant is registered as a biosimilar trastuzumab based on the totality of evidence including a randomized phase III study of NACT+Herceptin versus NACT+Ontruzant demonstrating similar pCR-rates (Pivot et al. J Clin Oncol 2018;36:968). However, no data exist for the efficacy of the combination of NACT with pertuzumab+Ontruzant (p+O). This investigator-initiated study was conducted to assess real world efficacy in HER2-positive EBC patients treated with NACT+p+O based on data from DBCG. DBCG has since 1977 provided guidelines for treatment of breast cancer and collected data from Danish hospital departments of surgery, pathology, and oncology prospectively on NACT, date and type of surgery and patho-anatomic findings. Methods: From the DBCG database, information was extracted for consecutive patients with unilateral early HER2-positive breast cancer registered to have received NACT+p+O from September 1, 2018 to August 31, 2019. pCR was defined as absence of residual invasive tumor in the breast and axillary lymph nodes (ypT0/Tis ypN0(i-)). Results: 215 patients received NACT+p+O. Median age was 54.8 years (range 24-81). NACT used, in combination with concurrent p+O, was cyclophosphamide+epirubicin followed by paclitaxel (62% on 6 cycles and 35% on 8 cycles) or other chemotherapy followed by paclitaxel (3%). Overall, 56% of patients achieved a pCR (Table). 68% of node-positive patients before receiving NACT+p+O had tumor-free axillary nodes after completing NACT+p+O. Conclusions: Real-world data from a nationwide population based study demonstrated a pCR-rate with NACT+p+O comparable to that seen in clinical studies with NACT+p+Herceptin (Chen et al. BMC Cancer 2019;19:973). pCR-rate was highly dependent on estrogen receptor (ER)-status and malignancy grade but not on clinical nodal status and tumor size. 68% of patients with cN+ converted to ypN0(i-). [Table: see text]
Influence of denosumab on disseminated tumor cells (DTC) in the bone marrow of breast cancer (BC) patients with neoadjuvant treatment: A GeparX translational substudy.
Authors: Wimberger Pauline , Blohmer Jens U. , Krabisch Petra , Link Theresa , Just Marianne , Sinn Bruno Valentin , Simon Eike , Solbach Christine , Fehm Tanja N. , Denkert Carsten , Kühn Cristin , Rhiem Kerstin , Tesch Hans , Kümmel Sherko , Petzold Andrea , Stoetzer Oliver J. , Meisel Cornelia , Kuhlmann Jan Dominik , Nekljudova Valentina , Loibl Sibylle 
Published: May 2020

580 Background: DTCs in the bone marrow are observed in up to 30% at primary diagnosis of BC and their presence is an independent prognostic factor for reduced survival. It was shown that antiresorptive therapy eradicates DTCs and improves prognosis in DTC-positive BC patients (pts). In the GeparX phase III prospective randomized trial, denosumab (a monoclonal IgG2-anti-RANKL-antibody) was investigated as add-on treatment to neoadjuvant chemotherapy (NACT) with two different nab-paclitaxel schedules in early high-risk primary BC. In a translational substudy, we analyzed for the first time the influence of short-term denosumab treatment (24 weeks) on the presence of DTCs. Methods: A total of 167 pts from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive pts were re-analyzed for DTCs after NACT±Denosumab. Results: Overall, 60/167 pts (35.9%) treated with NACT±Denosumab had a pathological complete response (pCR; 55.4% in TNBC, 43.3% in HER2+, 15.3% in HR+/HER2-). At baseline, 43/167 pts (25.7%) were DTC-positive and 41 of those were available for re-analysis of DTCs after NACT±Denosumab. DTC eradication was observed in 77.8% after NACT+Denosumab and in 69.6% after NACT alone (p = 0.726). Due to the limited number of pts eligible for DTC-re-analysis after NACT, a subtype specific analysis for the effect of denosumab was not possible. There was no significant association between pCR and i) the presence of DTCs at baseline (37.1% DTC-negative vs 32.6% positive, p = 0.71) or ii) the eradication of DTCs after NACT±Denosumab (36.7% vs 27.3%, p = 0.72). Notably, in TNBC, we observed a tendency that DTC-positivity at baseline or DTC-persistence after NACT could be associated with reduced pCR rate (40.0% in DTC-positive vs. 66.7% in DTC-negative pts, p = 0.16; 25% in DTC-persistent pts vs. 50% in DTC-eradicated pts, p = 0.59). Conclusions: Denosumab in addition to NACT does not improve pCR, but the suspected effect of denosumab on DTC eradication should be further analyzed in TNBC. Key words: GeparX trial, denosumab, disseminated tumor cells, bone marrow, neoadjuvant chemotherapy. Funding: GeparX and DTC substudy were financially supported by Amgen and Celgene. Clinical trial information: NCT02682693 .
One-year follow-up of health-related quality of life in the Swedish PREDIX HER 2 trial, evaluating docetaxel, trastuzumab sc, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2 positive breast cancer.
Authors: Brandberg Yvonne , Foukakis Theodoros , Andersson Anne , Bjohle Judith , Bosch Ana , Carlsson Lena , Einbeigi Zakaria , Fredholm Hanna , Isaksson-Friman Erika , Hellstrom Mats , Johansson Hemming , Lekberg Tobias , Lindman Henrik , Bergh Jonas C. S. , Hatschek Thomas 
Published: May 2020

590 Background: Neoadjuvant therapy combining docetaxel, trastuzumab and pertuzumab (DTP) was compared to trastuzumab emtansine (T-DM1) in the randomised phase II PREDIX HER2 trial. Patients, ≥18 years with HER2 positive breast cancer, ≥20mm or with verified lymph node metastases, were randomised to six courses of DTP (Standard group) or T-DM1 (Experimental group) before surgery. After operation patients in the Standard arm received two, and those in the Experimental arm four courses of EC. Since there were no differences in proportions of complete response at surgery and in the event-free survival between the groups, health-related quality of life (HRQoL) is of special interest. Methods: HRQoL was measured, using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 + EORTC QLQ-BR23, before randomisation, after six courses before surgery, at three months and one year after surgery. Results: Response rate for the questionnaires varied between 87% and 99% for the 198 included patients. There were no between-group differences at baseline. Results after six courses revealed statistically significant differences (p≤0.01), favouring the Experimental group on 12 out of 21 of the EORTC QLQ-C30 and BR23 variables (Physical-, Role-, and Social- functioning, Global quality of Life, Fatigue, Dyspnea, and Diarrhea, Body image, Sexual functioning, Sexual enjoyment, Systemic therapy side effects and Upset by hair loss). Three months after surgery, however, statistically significant differences in favour of the Standard group were found for six variables (Physical functioning, Nausea/vomiting, Dyspnea, Constipation, Systemic therapy side effects, Upset by hair loss). No other between group differences were found with one exception: lower levels of Breast symptoms in the Experimental group. One possible explanation is that patients in the Experimental group were still on chemotherapy at that assessment point, whereas the majority in the Standard group had terminated their treatment. No differences were found between the groups at the one-year after surgery follow-up, where the levels on most variables had returned to baseline values. Conclusions: HRQoL was better in the Experimental group during neoadjuvant treatment. Three months after surgery, however, HRQoL was in favour or the Standard arm. HRQoL returned to baseline levels for most variables at the one-year follow-up and no between-group differences were found. Clinical trial information: NCT02568839 .
A randomized phase II trial of secondary cytoreductive surgery (SCS) +/- carboplatin hyperthermic intraperitoneal chemotherapy (HIPEC) in patients (pts) with recurrent platinum-sensitive ovarian cancer (EOC).
Authors: Zivanovic Oliver , Chi Dennis , Zhou Qin , Iasonos Alexia , Makker Vicky , Grisham Rachel N. , Konner Jason A. , Diaz John Paul , Brown Amy K. , Langstraat Carrie L , Paroder Viktoriya , Soldan Krysten , Su Katy , Gardner Ginger J. , Jewell Elizabeth Lin , Long Kara , Tew William P. , Lichtman Stuart M. , Sonoda Yukio , O'Cearbhaill Roisin Eilish 
Published: May 2020

6016 Background: The role of HIPEC for recurrent EOC is not well defined. The aim of this phase II study was to determine the proportion of pts without evidence of disease progression at 24 months post SCS +/- intraoperative carboplatin HIPEC. Methods: After SCS to ≤ 0.5 cm residual visible disease pts were intraoperatively randomized to carboplatin HIPEC (800mg/m2 for 90 minutes) or no HIPEC. The HIPEC arm received 5 additional and the standard arm received 6 postoperative cycles of IV platinum-based chemotherapy without maintenance treatment. Based on an exact binomial single stage “pick the winner” design, each arm is considered “winner” if ≥ 17/49 pts are without evidence of disease progression at 24 months post SCS. Secondary objectives include postoperative grade ≥ 3 toxicity and complications within 4 weeks post SCS, and pharmacokinetics of carboplatin HIPEC. Results: Of 98 pts, 49 (50%) were randomized to the HIPEC arm. The arms were well balanced for age, stage, histology, BRCA mutation status, prior chemotherapy, and disease-free interval. Complete gross SCS was achieved in 94% of the standard and 82% of the HIPEC arm (p = 0.12). Bowel resection was performed more frequently in the standard (65%) compared to the HIPEC arm (37%; p = 0.008). Median operative time was shorter in the standard (296 minutes) compared to the HIPEC arm (475 minutes; p < 0.001). There was no perioperative mortality and no difference in use of ostomies, length of stay or postoperative toxicity. At a median follow-up of 27.7 months (range: 8.8-81.8 months) 70 of 98 pts progressed and 26 died with a median progression free survival (PFS) of 14.3 months (12.1-16 months) and a median overall survival (OS) of 55.2 months (47.7-not reached). At 24 months post SCS 32 pts progressed within 24 months in the standard versus 35 in the HIPEC arm. There was no statistically significant difference in median PFS (15.4 vs 12.3 months, p = 0.173) or median OS (69.2 vs 53.1 months, p = 0.317) between arms. These are preliminary efficacy estimates as 83/98 pts have a minimum of 24 months follow-up. Conclusions: The HIPEC arm did not reach the predefined “winner” endpoint; the standard arm is still undetermined as 6 pts did not reach 24 months follow-up. No perioperative mortality, and no increased perioperative morbidity or toxicity was seen with HIPEC. SCS with carboplatin HIPEC followed by 5 cycles of platinum-based chemotherapy was not superior to SCS without HIPEC followed by 6 cycles of platinum-based chemotherapy. Clinical trial information: NCT01767675.
Randomized double-blind placebo-controlled trial of primary maintenance vigil immunotherapy (VITAL study) in stage III/IV ovarian cancer: Efficacy assessment in BRCA1/2-wt patients.
Authors: Rocconi Rodney Paul , Grosen Elizabeth A. , Ghamande Sharad A. , Chan John K. , Barve Minal A. , Oh Jonathan , Tewari Devansu , Morris Peter C. , Stevens Erin E. , Bottsford-Miller Justin N. , Tang Min , Aaron Phylicia , Wallraven Gladice , Bognar Ernest , Manning Luisa , Nemunaitis John J. , Slomovitz Brian M. , Herzog Thomas J , Monk Bradley J. , Coleman Robert L. ,   Vigil Team
Published: May 2020

6017 Background: Vigil is an autologous tumor cell vaccine constructed from autologous harvested tumor tissue transfected with a DNA plasmid encoding GMCSF and bi-shRNA-furin thereby creating TGFβ expression control. Methods: A randomized double-blind placebo-controlled trial of Vigil vs. placebo was performed in advanced stage frontline OC patients. Relapse-free survival (RFS) and safety were endpoints. Patients who achieved complete clinical response were randomized [1:1 to placebo (control group, CG) or Vigil (Vigil group, VG)] after completion of frontline surgery and chemotherapy. All patients received 1 x 10e7 cells/ml of Vigil or placebo intradermally once a month for up to 12 doses. Results: Ninety-two patients were randomized with 91 patients in the per-protocol population (PP), (VG n=46; CG n=45). 62 patients were tested for BRCA1/2 status. VG showed no added overall toxicity compared to CG and no grade 4/5 toxicities were observed. Grade 2/3 toxic events were observed in 18% of CG patients (most common bone pain, fatigue) compared to 8% of VG patients (most common nausea, musculoskeletal pain). From time of randomization median RFS for all 91 patients was favorable in the VG (HR 0.69, one-sided p 0.088).Stratified by BRCA status, an advantage in RFS was seen in the BRCA1/2-wt patients in VG (19.4 mo) compared to CG (8 mo) (HR 0.51, 90% CI 0.26 – 1.01, one-sided p 0.050) from time of randomization and HR of 0.49 (90% CI 0.25 – 0.97, one-sided p 0.038) from time of surgery. Median time from surgery to randomization was 208.5 days (6.9 mo) in VG vs. 200 days (6.6 mo) in CG. 37.5% BRCA1/2-wt Vigil treated patients relapsed compared to 71% of placebo at time of data snap for analysis (HR 0.51, one-sided p 0.05), (median follow-up of 34.3 mo for all n=91 subjects). Germline and somatic BRCA1/2 molecular testing via central third party is underway on all 91 patients under continued blinded conditions to validate activity in BRCA1/2-wt. Conclusions: Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed RFS clinical benefit, particularly in BRCA1/2-wt disease. Clinical trial information: NCT02346747. [Table: see text]
Gastric-type adenocarcinoma of the cervix: Genomic drivers and clinical outcomes.
Authors: Sassine Dib , Straubhar Alli M. , Aghajanian Carol , Alektiar Kaled M. , Broach Vance , Cadoo Karen Anne , Jewell Elizabeth Lin , Kyi Chrisann , Leitao Mario M. , Mueller Jennifer Jean , Murali Rajmohan , O'Cearbhaill Roisin Eilish , Park Kay J. , Sonoda Yukio , Weigelt Britta , Zamarin Dmitriy , Abu-Rustum Nadeem , Friedman Claire Frances 
Published: May 2020

6030 Background: Cervical Gastric-type adenocarcinoma (CGA) is a non-HPV-associated adenocarcinoma, comprising 10% of all cervical adenocarcinomas (Park et al, 2019). The optimal management approach is unclear, given that most data in advanced cervical cancer is driven by HPV-positive disease. We summarize our experience with this rare tumor type at a large cancer center. Methods: A retrospective review was performed for all women diagnosed with CGA 6/1/2002- 7/1/2019. Patients who did not follow up after a single visit were excluded. Kaplan-Meier survival analysis was performed to determine progression-free survival (PFS) and overall survival (OS) from date of diagnosis. Tumors from a subset of patients were subjected to MSK-IMPACT targeted sequencing and analysis (Zehir et al, 2017). Results: A total of 68 women were identified; 47 met inclusion criteria. The median age at diagnosis was 52 years (range 27-83). The majority of patients were white (70%), an additional 19% were Asian. The majority of patients (60%, n=28) presented with advanced disease (FIGO 2018, stage II-IV), while 40% (n=19) were Stage I. Of note, 26% (n=12) had positive pelvic lymph nodes and 13% (n=6) had ovarian metastases at time of surgical resection. For upfront treatment: 13% (n=6) had surgery alone of whom 83% had stage 1 disease, 36% (n=17) had surgery followed by adjuvant therapy, 30% (n =14) received definitive chemo-radiation (CRT). All patients with stage IV disease 15% (n=7) received chemotherapy alone. At completion of primary treatment, 19% (n=9) of patients had persistent disease. In patients who received CCRT, 65% (n=22) recurred, the majority (64%) within 12 months of completion of upfront therapy. Pelvic recurrence was the most common site (n=14, 64%). With a median follow up time of 30 months (range 1-159), the median PFS for Stage I was 34.4 months, compared to 17.5 months in patients with Stage II-IV disease (p= 0.29). Of the 24 patients that had MSK-IMPACT, the most common mutation was TP53 (n=16, 64%) followed by mutations in the RAS pathway (n=8, 33%), PIK3CA (n=3, 12.5%), STK11 (n=3, 12.5%), and ERBB2 alterations (n=2, 8.3 %). 2 (8.3%) women enrolled on a clinical trial based on their NGS results, one targeting ERBB2 and one targeting PIK3CA. Conclusions: Consistent with prior published literature, CGA is an aggressive form of cervical cancer with poor median OS in the advanced setting. With universal HPV vaccination, HPV negative cervical cancer will represent a larger percentage of newly diagnosed cancers and further research is needed to identify the optimal management approach.