bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-related quality of life in the Swedish PREDIX HER2 trial, evaluating docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer.
Authors: Brandberg Yvonne , Andersson Anne , Bjohle Judith , Bosch Ana , Carlsson Lena , Dreifaldt Ann Charlotte , Einbeigi Zakaria , Fredholm Hanna , Isaksson-Friman Erika , Foukakis Theodoros , Elinder Ellinor , Hellstrom Mats , Johansson Hemming , Lekberg Tobias , Lindman Henrik , Bergh Jonas C. S. , Hatschek Thomas 
Published: May 2019

583 Background: Neoadjuvant therapy combining docetaxel, trastuzumab and pertuzumab (DTP) was compared to trastuzumab emtansine (T-DM1) in the randomized phase 2 PREDIX HER2 trial. Patients, ≥18 years with HER2 positive breast cancer, ≥20mm or with verified lymph node metastases, were randomized to six courses of DTP (Standard arm) or T-DM1 (Experimental arm). Primary endpoint was pathological objective response to primary medical therapy at post-treatment surgery. Health related quality of life (HRQoL) was a secondary outcome, and is of specific interest as there was no difference between the randomization groups regarding the main endpoint (results presented in a separate abstract sent to ASCO 2019, Bergh et al.). Methods: Of 202 randomized patients, 190 are available for evaluation at this point. HRQoL was measured, using EORTC QLQ-C30 + EORTC QLQ-BR23, at baseline before randomization and after six courses. Results: No differences between the randomization arms were found at baseline. Results after six courses, based on 163 patients (86%) and adjusted to baseline values, revealed statistical significant differences (p≤0.01), favoring the experimental T-DM1 arm on 7 out of 15 of the EORTC QLQ-C30 variables (Physical functioning, Role functioning, Social functioning, Global quality of Life, Fatigue, Dyspnea, and Diarrhea). For the breast cancer specific questionnaire (EORTC-BR23), the experimental arm scored statistically significantly better on 5 out of 7 subscales (Body image, Sexual functioning, Sexual enjoyment, Systemic therapy side effects and Upset by hair loss). All of the statistical significant differences were of moderate or large clinical significance (≥10 scale scores). No differences between the randomization arms were found for the remaining HRQoL variables. Conclusions: The experimental arm reported better HRQoL than the control arm after six courses. Trastuzumab emtansine may be a useful treatment alternative due to better HRQoL and lower toxicity. Clinical trial information: NCT02568839.
Development and external validation of a deep learning model for predicting response to HER2-targeted neoadjuvant therapy from pretreatment breast MRI.
Authors: Vulchi Manasa , El Adoui Mohammed , Braman Nathaniel , Turk Paulette , Etesami Maryam , Drisis Stylianos , Plecha Donna , Benjelloun Mohammed , Madabhushi Anant , Abraham Jame 
Published: May 2019

593 Background: HER2-targeted neoadjuvant chemotherapy (NAC) possesses heterogeneous outcomes and currently lacks clinically-accepted markers of response. A means of predicting which patients will benefit prior to the treatment could reduce toxicity and the delay to effective intervention. Computational analysis of MRI via a deep neural network has shown promise in identifying NAC responders among mixed receptor subtype and treatment regimen cohorts, but faces challenges due to reproducibility across institutions and has not yet been explored in the context of HER2-targeted therapy. Here we present a deep learning approach for predicting response to HER2-targeted NAC from pre-treatment MRI. Methods: 100 HER2+ breast cancer patients who received NAC with docetaxel, carboplatin, trastuzumab, and pertuzumab at Cleveland Clinic (CCF) and had pre-treatment contrast-enhanced MRI’s were included in this analysis. 49 patients achieved pathological complete response (pCR, ypT0/is), while 51 patients retained presence of residual disease following NAC (non-pCR). 85 patients were used to train a convolutional neural network to predict pCR based on pre- and post-contrast MRI images, and the model design was optimized based on performance within a 15 patient internal validation cohort. An external, held-out testing dataset consisting of 28 patients (16 pCR, 12 non-pCR) imaged and treated at University Hospitals (UH) Cleveland Medical Center was used to validate the performance of the model. Performance was assessed by area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. A multivariable model incorporating age, hormone receptor status, stage, and tumor size was developed and similarly evaluated. Results: The neural network was able to predict the response to HER2-targeted NAC in the internal validation cohort (AUC = 0.93) as well as in an independent cohort from a separate institution (AUC = 0.85). This model offered superior performance compared to a multivariate clinical model, which achieved AUC = 0.67 and AUC = 0.52, in internal validation and external held-out testing cohorts, respectively. Conclusions: Deep learning analysis of contrast-enhanced MRI could be used to better target anti-HER2 therapy by pre-treatment prediction of response.[Table: see text]
Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicenter randomized controlled trial.
Authors: Chen Ming-Yuan , Yang Qi , Hong Minghuang , Hong Ming-Huang 
Published: May 2019

6004 Background: Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil (PF) resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival (LRRFS) and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. Methods: Our trial was a randomized, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² d1-5) every three weeks for two cycles before CCRT. Both groups were treated with 80 mg/m² cisplatin every three weeks concurrently with radiotherapy. The primary endpoints were DFS and DMFS. We did efficacy analyses in the 476 randomized patients (intention-to-treat population). Results: After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval (CI) 67.7-79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8-69.4) in the CCRT alone group (P = 0.005). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9-87.7) than in the CCRT alone group (73.1%, 95% CI 67.2-79.0, P = 0.013). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (P = 0.045). There were no significant differences in the rate of grade 3–4 late adverse events during follow-up between the two groups. Conclusions: IC followed by CCRT provides long-term DFS, DMFS, and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients. Clinical trial information: NCT00705627.
Palbociclib plus cetuximab versus placebo plus cetuximab in platinum-resistant, cetuximab-naive, HPV-unrelated head and neck cancer: A double-blind randomized phase II trial (PALATINUS).
Authors: Adkins Douglas , Lin Jin-Ching , Sacco Assuntina Gesualda , Ley Jessica C. , Oppelt Peter , Shen Qi , Kern Kenneth Alan , Thurm Holger C. , Wang Shaw-Ling , Martini Jean-Francois , Hoffman Justin , Melichar Bohuslav , Tahara Makoto 
Published: May 2019

6013 Background: Cetuximab monotherapy results in a median overall survival (OS) of approximately 6 months (mo) in platinum-resistant recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). HNSCC unrelated to human papillomavirus (HPV) is driven by hyperactivation of the CDK4/6 and cyclin D1 (CD1) regulatory complex, resulting in cell cycle progression and tumor growth, suggesting that CDK4/6 inhibition can be a rational therapeutic strategy in this setting. Palbociclib (PAL) is a selective CDK4/6 inhibitor that may reverse cetuximab resistance by countering the actions of deregulated CD1. PAL plus an epidermal growth factor receptor inhibitor synergistically reduced cell viability of HPV-unrelated HNSCC cell lines. In a single-arm, multicenter trial of platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC, PAL in combination with cetuximab resulted in a median OS of 9.5 mo. Methods: In a double-blind randomized phase II trial, patients (pts) with platinum-resistant, cetuximab-naïve, HPV-unrelated HNSCC were treated with cetuximab plus either PAL (arm A) or placebo (arm B). Pts were stratified by performance status (PS) and prior immunotherapy (IT). 120 pts were required for 1:1 randomization to have ≥ 80% power to detect a hazard ratio (HR) of 0.6 (corresponding to a median OS of 10 mo in arm A and 6 mo in arm B) using a 1-sided log-rank test P=0.10). Key secondary endpoints included progression-free survival (PFS), adverse events (AEs), and p16 status. Results: Pts (n=125) were randomized (arm A, 65; arm B, 60). PS and prior IT were balanced between the arms. Median (95% CI) follow-up for OS was 15.9 (15.0–19.4) mo. Median OS was 9.7 (7.3–13.9) mo in arm A and 7.8 (6.7–10.6) mo in Arm B (stratified by PS: HR=0.82 [95% CI, 0.54–1.25], P=0.18). Median PFS was 3.9 mo in arm A and 4.6 mo in arm B (stratified by PS: HR=1.00 [0.7–1.5], P=0.5). Hematologic AEs were more common in arm A. Only 11 pts (9%) received IT after being treated on the trial. Conclusions: Among pts with platinum-resistant, HPV-unrelated HNSCC, PAL plus cetuximab resulted in a trend of prolongation of median OS compared with cetuximab. Clinical trial information: NCT02499120.
Results of a phase 2a, multicenter, open-label, study of RM-1929 photoimmunotherapy (PIT) in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).
Authors: Cognetti David M. , Johnson Jennifer Maria , Curry Joseph M. , Mott Frank , Kochuparambil Samith Thomas , McDonald Darren , Fidler Mary J. , Stenson Kerstin , Vasan Nilesh R. , Razaq Mohammad , Campana John P. , Biel Merrill A. , Gillenwater Ann M. 
Published: May 2019

6014 Background: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces selective and rapid necrosis of the cancer cells, with minimal damage to surrounding tissue. Methods: A phase 2a, multicenter, open-label, study of RM-1929 PIT in patients with locoregional, rHNSCC who could not be satisfactorily treated with surgery, radiation, or platinum chemotherapy was conducted to evaluate the safety and efficacy of the drug, RM-1929. For each treatment, nonthermal red light (690 nm) was applied to the tumors 24 hours post IV infusion of the drug. Surface illumination was administered for superficial tumors and interstitial illumination via intratumoral placement of fiber optic diffusers for deep tumors. Therapeutic response was assessed using CT RECIST 1.1 by an independent blinded radiologist. Results: Thirty rHNSCC patients were enrolled. There were no dose-limiting toxicities and one Grade 1 photosensitivity reaction. Most reported AEs were mild to moderate in severity with 96.7% (29/30) of patients with Grade 1 and 83.3% (25/30) with Grade 2, respectively. There were 13 (43.3%) patients who had at least one SAE. 86% (19/22) of SAEs were deemed unlikely related to treatment, including all 3 fatal SAEs. Three SAEs were reported to be possibly/probably related to treatment (site/oral pain, tumor hemorrhage, and airway obstruction). ORR was 50% (15/30) with 16.7% (5/30) CR and 86.7% (26/30) DCR. Median PFS and OS results will be forthcoming. Conclusions: These data indicate that RM-1929 PIT treatment was generally well tolerated with majority of AEs as mild to moderate in severity. Preliminary data showed favorable response rates in a heavily pre-treated population. A global phase 3 clinical trial is currently underway. Clinical trial information: NCT02422979.
Primary analysis of phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with locally advanced cutaneous squamous cell carcinoma (laCSCC).
Authors: Migden Michael Robert , Khushalani Nikhil I. , Chang Anne Lynn S. , Rischin Danny , Schmults Chrysalyne D. , Hernandez-Aya Leonel Fernando , Meier Friedegund Elke , Schadendorf Dirk , Guminski Alexander David , Hauschild Axel , Wong Deborah J.L. , Daniels Gregory A. , Berking Carola , Jankovic Vladimir , Stankevich Elizabeth , Booth Jocelyn , Li Siyu , Lowy Israel , Fury Matthew G. , Lewis Karl D. 
Published: May 2019

6015 Background: Cemiplimab (REGN2810) produced substantial antitumor activity with durable responses in Phase 1 CSCC expansion cohorts and Phase 2 metastatic (m) CSCC cohort. We now present the primary analysis of the Phase 2 laCSCC cohort (NCT02760498; data cutoff date: Oct 10, 2018). Methods: Pts with laCSCC received cemiplimab 3 mg/kg IV every 2 weeks (Q2W). Tumor measurements were performed Q8W. The primary objective was to evaluate objective response rate (ORR; complete response [CR] + partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified WHO criteria for photos). Results: 78 pts were enrolled (59 M/ 19 F; median age: 74 years; ECOG PS: 0 in 38 pts, 1 in 40 pts; primary CSCC site: head/neck in 79.5%; prior systemic therapy: 15.4%; prior radiotherapy: 55.1%). Median duration of follow-up was 9.3 months (range: 0.8–27.9). ORR by central review was 43.6% (95% CI: 32.4–55.3; 10 CRs and 24 PRs); investigator-assessed (INV) ORR was 52.6% (95% CI: 40.9–64.0; 13 CRs and 28 PRs). Median duration of response (DOR) has not been reached. The longest DOR at data cut-off was 24.2 months and was still ongoing. Durable disease control rate (stable disease or response for ≥16 weeks) was 62.8% (95% CI: 51.1–73.5). Median observed time to response was 1.9 months (range: 1.8–8.8). Median progression-free and overall survival have not been reached. Tumor PD-L1 status is available for 48/78 pts, tumor mutational burden analysis (from targeted exome panel) is ongoing for ≥40/78 pts; response correlation analyses are planned. The most common treatment-emergent adverse events (AEs; all grades, Grade ≥3) were fatigue (42.3%, 1.3%), diarrhea and pruritus (both 26.9%, 0%), and nausea (21.8%, 0%). INV grade ≥3 immune-related AEs occurred in 10.3% of pts. One pt died due to an unknown cause that was assessed as treatment-related. Conclusions: Cemiplimab 3 mg/kg Q2W showed substantial antitumor activity, durable responses, and acceptable safety profile in pts with laCSCC. These data strongly support the recent FDA approval of cemiplimab-rwlc for pts with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation. Clinical trial information: NCT02760498.
Recombinant humanized anti-PD-1 monoclonal antibody (JS001) in patients with refractory/metastatic nasopharyngeal carcinoma: Interim results of an open-label phase II clinical study.
Authors: Wang Fenghua , Wei Xiao-Li , Feng Ji Feng , Li Qi , Xu Nong , Hu Xi-Chun , Jiang Yi , Liao Wangjun , Zhang Qingyuan , Yuan Xianglin , Huang Haixin , Chen Ye , Dai Guanghai , Shi Jianhua , Shen Lin , Yang Shujun , Shu Yongqian , Liu Yunpeng , Xu Rui-hua ,   Shanghai Junshi Biosciences Co., Ltd.
Published: May 2019

6017 Background: Metastatic nasopharyngeal cancer (NPC) patients progressed afterstandardtherapy have limited treatment options. Toripalimab, also known as JS001, a humanized IgG4 antibody specific for human PD-1, has been approved for 2nd line treatment of metastatic melanoma in China. Here we report the results from a phase IIstudy in metastatic NPC patients treated with toripalimab.(Clinical trial ID: NCT02915432). Methods: This multi-center, open-label, phase II registration study is designed to evaluate the safety and efficacy of toripalimab in metastaticNPC patients who have failed systemic treatment. Toripalimabis given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity.Tumor PD-L1 expression, plasma EBV DNA level and other biomarkerswill be correlatedwith clinical response. Results: Enrollment of 190chemo-refractory metastatic NPCpatients was completed by Feb 2019 from 17 participating centers. The median age was 46 years, with 89.5% patients received at least 2 lines of prior systemic therapies. Treatment related adverse events (TRAE)occurred in 92% patients, which were mostly grade 1 or 2.Common TRAE includedanemia, hypothyroidism, AST increased, proteinuria, pyrexia, cough, constipation, ALT increased, hypoalbuminemia and pruritus.Grade 3 or higherTRAEoccurred in 25% patients.By the cut-off date of Jan 7 2019, among 135 evaluable patients, 3 complete responses, 31 partial responses and 40 stable diseaseswere observed for an objective response rate (ORR) of 25.2% and a disease control rate of 54.8%. PD-L1 expression results were obtained from 125 patients and 45.6% (57/125) were PD-L1+.PD-L1+ patientsachieved slightly higherORR than PD-L1- patients, 29.8% versus 22.1%. In addition, an average drop of 47-fold plasma EBV DNA copy number was observed in responding patients, which typically proceeded the radiographic identification of clinical benefit. Conclusions: Toripalimab has demonstrated a manageable safety profileand encouraging clinical activity in the largest check-point blockade study in NPC to date. A change in plasma EBV DNA copy number might serve as a predictive marker for favorable clinical response. Patients will be continuously monitored for additional safety and survival readouts. Clinical trial information: NCT02915432.
Alliance A091404: A phase II study of enzalutamide (NSC# 766085) for patients with androgen receptor-positive salivary cancers.
Authors: Ho Alan Loh , Foster Nathan R. , Zoroufy Alexander J. , Worden Francis P. , Price Katharine Andress Rowe , Adkins Douglas , Bowles Daniel W. , Kang Hyunseok , Burtness Barbara , Sherman Eric Jeffrey , Morton Roscoe F. , Katabi Nora , Munster Pamela N. , Schwartz Gary K. 
Published: May 2019

6020 Background: A subset of salivary gland cancer (SGCs) express the androgen receptor (AR). This phase II trial evaluated the anti-androgen enzalumatide (Astellas) for patients with AR+ SGCs. Methods: Locally advanced/unresectable or metastatic AR+ SGCs were enrolled (AR status was centrally confirmed). Prior therapy with AR-targeted drugs was allowed. Enzalutamide 160 mg orally once daily was given (1 cycle= 28 days). The primary endpoint was confirmed response (RR) according to RECIST v1.1 within the first 8 cycles. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. A Simon-Optimal two-stage design was used to detect a 20% RR (vs. 5%) (alpha = 5%; beta = 90%). > 1 response(s) in the first 21 would trigger accrual to 41; > 4 responses would be considered promising. Results: 46 eligible patients (pts) were enrolled (40 M, 6 F; median age 65) in 22 months. In the first 21 pts, we initially had 2 confirmed PRs allowing for full study accrual, though one was later changed to stable disease. Among the 46 pts, 7 had PR as best response, though only 2 were confirmed within the first 8 cycles (4% (95% CI: 0.5-15%). Two other PRs did not count towards the primary endpoint due to 1) development beyond 8 cycles (cycles 12-18) and 2) a confirmatory scan completed <4 weeks apart. The other 3 pts with unconfirmed PR developed progression of disease (PD) after the first PR scan. 24 pts had stable disease; 15 pts PD as best response. Among 11 pts previously treated with AR-targeted therapy, best responses were 1 confirmed PR, 7 SD, 3 PD. With a median follow-up of 11.7 months (mo), OS at 12 mo was 66% (95% CI: 52-83%), PFS at 12 mo was 24% (95% CI: 14-42%), and median PFS was 5.5 mo (95% CI: 3.7-7.3). Conclusions: This is the first prospective trial evaluating an antiandrogen alone for AR+ SGCs. The failure to meet the protocol-defined measure of success was due in part to the lack of durability of initial responses. The clinical activity observed suggests the AR-dependence of AR+ SGCs, even among those previously treated with other hormonal therapies. Support: U10CA180821, U10CA180882; Astellas; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02749903.
CDX3379-04: Phase II evaluation of CDX-3379 in combination with cetuximab in patients with advanced head and neck squamous cell carcinoma (HNSCC).
Authors: Bauman Julie E. , Saba Nabil F. , Wise-Draper Trisha Michel , Adkins Douglas , O'Brien Paul E. , Heath-Chiozzi Margo , Golden Philip , Drescher Jennifer , Alvarado Diego , Gedrich Richard , Cohen Roger B. 
Published: May 2019

6025 Background: CDX-3379, an anti-ErbB3 monoclonal antibody with a half-life-extending YTE modification in its Fc region, binds a unique epitope that locks ErbB3 in an inactive form and inhibits ErbB3 signaling, the latter implicated in tumor growth/resistance to anticancer therapies. CDX-3379 enhances antitumor activity of targeted therapies in preclinical models. In a Phase 1 clinical study, CDX-3379 was well-tolerated alone and in combination with cetuximab. A durable complete response (CR) to CDX-3379 + cetuximab was observed (8.3 months) in a patient (pt) with cetuximab-refractory HNSCC (Falchook ASCO 2016). Methods: This open-label phase 2 study (NCT03254927) was designed to enroll up to 30 pts with advanced, HPV-, HNSCC, previously treated with cisplatin, anti-PD-1 antibodies, and cetuximab-resistant (progression within 6 months), according to a Simon’s 2-stage design (13 evaluable pts in Stage 1 with ≥1 objective response allows enrollment of 14 more pts in 2nd stage). Pts receive CDX-3379 (initial dose 12 mg/kg IV every 21 days) + cetuximab (loading dose 400 mg/m2; 250 mg/m2 IV weekly) until disease progression/toxicity. Endpoints include objective response rate (primary), progression-free and overall survival, safety, pharmacokinetics, immunogenicity, and exploratory biomarkers. Results: Stage 1 accrual is complete with 14 evaluable pts treated. All pts were heavily pretreated; prior therapies included surgery (10/14) and chemotherapy (13/14). All pts had prior radiation, cetuximab and PD-1 targeted therapy. One confirmed ongoing CR (8.1+ months) was observed. 7/14 pts experienced stable disease (SD), including 4 with tumor shrinkage (8-27.5% reduction). Three pts continue treatment. Treatment-related adverse events were generally grade 1-2 and included diarrhea (53%), hypokalemia (20%), prolonged QT interval (13%) and rash (13%). Conclusions: CDX-3379 in combination with cetuximab is well tolerated with the primary toxicity of diarrhea. Signs of antitumor activity were observed in these cetuximab-resistant HNSCC pts, including an ongoing, durable CR. Complete stage 1 results will be presented. Clinical trial information: NCT03254927.