bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant giredestrant + palbociclib (P) vs. anastrozole (A) + P in postmenopausal women with estrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+, HER2– eBC): Patient (pt)-reported outcomes (PROs) in the randomized, open-label, international phase II coopERA BC study.
Authors: Park Yeon Hee , Quiroga Vanesa , Fasching Peter A. , Bardia Aditya , López-Valverde Vanesa , Badovinac Crnjevic Tanja , Steinseifer Jutta , Devine Jacob , Hurvitz Sara A. 
Published: June 2023

591 Background: Endocrine therapies (ETs) are the therapeutic mainstay for ER+ BC but persistent adverse events (AEs; eg joint pain, especially with aromatase inhibitors) negatively impact quality of life, and resistance impacts efficacy. Giredestrant, a highly potent, nonsteroidal, oral selective ER antagonist and degrader (PO SERD), may help address these issues. coopERA BC (NCT04436744) evaluated giredestrant in eBC and met its primary endpoint, demonstrating a greater reduction of Ki67 with giredestrant vs. A after 2 weeks. Giredestrant was well tolerated as a single agent and with P. We report exploratory PRO analyses. Methods: Pts with cT1c-cT4a-c (≥ 1.5 cm within cT1c) ER+, HER2– untreated eBC and baseline Ki67 score ≥ 5% were randomized 1:1 to 30 mg PO daily (QD) giredestrant or 1 mg PO QD A on days (D)1–14 of a window-of-opportunity phase. A 16-week neoadjuvant phase added 125 mg PO QD P on D1–21 of four 28-D cycles. Presence/frequency/severity/interference of relevant symptomatic AEs were assessed at Cycles 1–4 via NCI PRO-CTCAE library items; overall burden due to AEs, via FACT-G item GP5. Results: PRO completion rates were > 80% at all time points. PRO-CTCAE postbaseline frequency scores were comparable between arms and mostly 0/1 (never/rare; reported for: Diarrhea > 80% of pts; hot flash > 60%; joint pain > 65%; nausea > 90%; vomiting > 90%). No rash was reported by > 90% of pts; fatigue at 0/1 severity (none/mild) by > 75% and at 0/1 interference (none at all/a little bit) by 80%. Hot flash frequency scores of 2–4 (occasionally/frequently/almost constantly) were reported by 30% of pts in the giredestrant + P arm and 37% in the A + P arm; joint pain frequency scores of 2–4, by 25% and 35%. Worst postbaseline scores of 3–4 are shown in the table. FACT-G GP5 showed greater proportions of “improved/no change” responses in the giredestrant + P than the A + P arm at Cycles 2–4 (Cycle 2 75%; Cycle 3 71%; Cycle 4 68% vs. 62%; 66%; 53%), and smaller proportions of “worsened” responses (25%; 29%; 32% vs. 38%; 34%; 47%). Conclusions: This is the first analysis to our knowledge of PROs with a PO SERD in eBC; it showed that most pts reported minimal symptomatic AEs at frequency and severity levels that were generally numerically lower in the giredestrant + P than the A + P arm (particularly joint pain). Furthermore, there were numeric trends towards greater stability and improvement and less worsening of treatment burden in the giredestrant + P arm. Studies to further assess giredestrant’s clinical benefit are ongoing in the adjuvant setting. Clinical trial information: NCT04436744 . [Table: see text]
Taxane combined with lobaplatin or anthracycline for neoadjuvant treatment of triple-negative breast cancer: A single-center, randomized, controlled, phase-II clinical study.
Authors: Wang Cheng , Wang Rui , Zhang Guozhi , Wan Andi , Xiong Siyi , Yuan Long , Tian Hao , Ma Dandan , Jiang Jun , Zhang Yi , Qi Xiaowei 
Published: June 2023

593 Background: Previously, we showed that addition of lobaplatin (L) to taxane combined with anthracycline could improve the pathologic complete response (pCR) rate and lengthen survival significantly if employed as neoadjuvant therapy in patients with triple-negative breast cancer (TNBC). We evaluated the efficacy and safety of neoadjuvant chemotherapy of taxane (T) combined with lobaplatin (L) or anthracycline (E) for patients with TNBC. Methods: Ninety-five patients with TNBC (stage I–III) who had not undergone any type of treatment were divided randomly into two groups: TL (docetaxel at 75 mg/m2 and lobaplatin at 30 mg/m2, D1, one cycle = 21 days, a total of six cycles) or TE (docetaxel at 75 mg/m2 and epirubicin at 80 mg/m2, D1, one cycle = 21 days, a total of 6 weeks or epirubicin at 80 mg/m2 and cyclophosphamide at 600 mg/m2, sequential docetaxel at 75 mg/m2, D1, one cycle = 21 days, a total of eight cycles). Efficacy was evaluated every two cycles. The final surgical procedure was completed after fulfillment of neoadjuvant chemotherapy. The primary endpoint was the total pathologic complete response (tpCR) rate. The secondary endpoints were the objective response rate (ORR), safety, event-free survival (EFS), and overall survival (OS). The exploratory endpoint was biomarker analysis. Results: From June 2019 to November 2022, 97 patients were screened. Finally, 95 patients were enrolled. The median age of the study cohort was 49 years. Nine patients (9.5%) had stage-I disease, 61 patients (64.2%) had stage II, and 25 patients (26.3%) had stage III. Sixty-five patients (68.4%) had Ki67 ≥40% and 30 patients (31.6%) had Ki67 < 40%. Seventy patients (73.7%) were cytokeratin (CK)5/6+ and 25 patients (26.3%) were CK5/6−. Of 95 patients, 47 were in the TL group and 48 in the TE group. The tpCR rate in the TL group was 46.8% (22/47), which was significantly higher than that in the TE group (22.9% (11/48); odds ratio (OR) = 2.960, 95% confidence interval (CI) = 1.223–7.164, P = 0.016). The ORR in the TL group was 95.7% (45/47), which was significantly higher than that in the TE group (75.0% (36/48); OR = 27.500, 95% CI = 1.576–35.683, P = 0.011). The prevalence of grade III/IV neutropenia in the TE group was 41.0% (9/22), which was significantly higher than that in the TL group (7.7% (2/26); OR = 8.308, 95% CI = 1.557–44.320, P = 0.013). There was no significant difference in the prevalence of other adverse reactions between the two groups. Conclusions: In the neoadjuvant treatment of TNBC, the TL regimen had a higher tpCR rate and ORR than those of the TE regimen, and was safer. Clinical trial information: ChiCTR1900023776 .
Longitudinal MRI-based fusion novel model to predict pathological complete response in breast cancer treated with neoadjuvant chemotherapy: A multicenter, retrospective study.
Authors: Wang Kun , Huang Yuhong 
Published: June 2023

599 Background: Accurate identification of pCR to neoadjuvant chemotherapy (NAC) is important for determining appropriate surgery strategy and guiding the resection extent in breast cancer. However, a non-invasive tool to predict pCR accurately is lacking. Our study aims to develop ensemble learning models using longitudinal multiparametric MRI to predict pCR for each molecular subtype of breast cancer. Methods: In this study, all patients underwent pre-NAC and post-NAC MRI examinations, and we collected multiparametric MRI sequences. Post-operation pathologic results were used to determine the pathologic complete response (pCR). We extracted 14676 radiomics and 4096 deep learning features and calculated a set of additional delta-value features. Then in the primary cohort (n = 409), inter-class correlation coefficient test, U-test, Boruta and the least absolute shrinkage and selection operator (LASSO) regression were used to select the most optimal feature set for each subtype of breast cancer. Finally, 20, 15 and 13 features were selected to construct the models based on 5 specific algorithms with cross-validation method for predicting pCR in HR+/HER2-, HER2+ and TNBC subtypes. The ensemble learning strategy was used to integrate the single-modality models outputs and improve the prediction performance. The diagnostic performances of models were evaluated in the three external cohorts with lager sample size of patients (n = 343, 170 and 340, respectively). Results: A total of 1262 patients with breast cancer from four centers were enrolled in this study, and pCR rates were 10.6% (52/491), 54.3% (323/595) and 37.5% (66/176) in HR+/HER2-, HER2+ and TNBC subtype. After model development, the Multi-Layer Perception (MLP) neural network yields the best diagnostic performances in all subtypes and feature sets. In the three subtypes, the stacking model integrating pre-, post- and delta- models yielded the highest AUCs of 0.959, 0.974 and 0.958 in the primary cohort, and AUCs of 0.882-0.908, 0.896-0.929 and 0.837-0.901 in the three external validation cohorts, respectively. In all subtypes, the stacking model had accuracies of 85.0%-88.9%, sensitivities of 80.0%-86.3%, and specificities of 87.4%-91.5% in the external validation cohorts. Conclusions: Our study established a novel tool to predict the responses of breast cancer to NAC and achieve excellent performance. The models could help to determine post-NAC surgery strategy for patients with breast cancer.
Results of the multicenter phase II FRAIL-IMMUNE trial evaluating the efficacy and safety of durvalumab combined with weekly paclitaxel carboplatin in first-line in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) not eligible for cisplatin-based therapies.
Authors: Fayette Jerome , Cropet Claire , Gautier Julien , Toullec Clemence , Burgy Mickael , Bruyas Amandine , Sire Christian , Lagrange Aurelie , Clatot Florian , Calderon Benoit , Vinches Marie , Iacob Mariana , Martin Laurent , Neidhardt Berard Eve Marie , Kaminsky Marie-Christine , Vansteene Damien , Salas Sébastien , Champagnac Anne , Pérol David , Bourhis Jean 
Published: June 2023

6003 Background: For pts with R/M SCCHN, new standard of care (SoC) has been recently established with pembrolizumab either alone or combined with platin-5FU (KN 048 – median Overall Survival (OS): 13 months when combined). For pts who need chemotherapy, platinum-5FU-pembrolizumab as first-line treatment appears associated with substantial toxicity that precludes its use in fragile patients. In this context, we investigated the efficacy and tolerance of PDL-1 inhibition with durvalumab combined with weekly carboplatin-paclitaxel as first-line treatment in frail R/M SCCHN pts. Methods: This single-arm phase II study enrolled pts in first-line of their R/M SCCHN and not eligible to standard cisplatin-based CT with an ECOG PS of 0 or 1. Pts received 4 cycles of CT (carboplatin AUC2; paclitaxel 80mg/m² both at D1, D8, D15) and durvalumab (D) 1500mg repeated every 4 weeks for a maximum of 12 months. The primary endpoint was OS Rate at 12 months (m). The study used a Fleming A’Hern design (inefficacy boundary: 47% and target efficacy: 65%), requiring 38 successes among 64 pts. Secondary endpoints were Progression-Free Survival (PFS), Time to Treatment Failure (TTF), objective response rate (ORR) and tolerance. Results: 64 pts (median age 69.5y; 90.6% males, 62.5% PS1) were included, regardless of their PDL-L1 status. Primary tumors were mainly located in oropharynx (37.5%) and larynx (28.1%) with 37.3% PD-L1 CPS≥20. 54.9% were metastatic. The efficacy rule for OS was met with 40 pts (62.5%, unilateral 95%CI: [51.5% - ]) alive at 12m. With a median follow-up of 27.1 m, median OS was 18.0 m (95% CI [11.9-NR]) and the 24m-OS rate was 45% [32%-57%]. Median PFS was 7.0 m (95% CI [5.4-9.9]) and median TTF was 6.0 m (95% CI [4.7-9]). 44/62 pts (71%) achieved an OR (11.3% complete response and 59.7% partial response). Median duration of response was 5.9 m (95% CI [3.4-9.6]). 20.3% of pts experienced G≥3 adverse events related to D, Toxicity led to permanent discontinuation of D in 3.1% of pts. No D-related death was reported. Conclusions: This study performed in fragile patients not amenable to cisplatin-based CT met its primary endpoint on OS and showed a 18 months median OS rate. This combination of durvalumab with weekly carboplatin/paclitaxel was associated with a favorable toxicity profile. Clinical trial information: NCT0372967 .
NEOSPACE trial: Neoadjuvant pembrolizumab-gemcitabine-cisplatin followed by concurrent pembrolizumab-chemoradiation and maintenance pembrolizumab for stage IVA nasopharyngeal cancer (NPC).
Authors: Hui Edwin P , Ma Brigette , Lim Darren Wan-Teck , Lam WK Jacky , Soong Yoke Lim , Li Leung , Wong Kenneth C.W. , Lam Daisy , Mok Florence , Tong Macy , Poon Darren MC , Wong Chi Hang , Mo Frankie , King Ann Dorothy , Lo Kwok-Wai , Chan Jason Y.K. , Chan KC Allen , Chan Anthony T. C. 
Published: June 2023

6010 Background: Stage IVA NPC had the worst prognosis despite the current standard of neoadjuvant chemotherapy and concurrent chemoradiation (CRT). There is no safety and efficacy data combining immune checkpoint inhibitor (ICI) and CRT in NPC. Methods: We conducted an open label, single arm, multi-site, phase 2 clinical trial in AJCC 8th Edition Stage IVA (T4 and/or N3, M0) WHO type 2/3 Epstein Barr virus (EBV) +ve NPC (Clinical trial register NCT03734809). The experimental treatment consisted of neoadjuvant pembrolizumab (200 mg D1), gemcitabine (1000 mg/m2 D1+8) and cisplatin (80 mg/m2 D1) q3w x2 followed by concurrent pembrolizumab (200 mg x3 week 1, 4 and 7) and cisplatin (40 mg/m2 weekly x7) during intensity-modulated radiation (IMRT), and maintenance pembrolizumab 200 mg q3w x12 from 4 weeks post-RT. By Fleming one-stage design (type I error 0.05, power 0.80, 10% drop out), planned sample size is 46. Primary endpoint is 2-year (yr) progression free survival (PFS). Secondary endpoints include safety and tolerability. Plasma EBV DNA (pEBV DNA) was monitored. Results: Accrual was completed with 46 subjects recruited at two study sites from May 2019 to June 2022 in Hong Kong (n=31) and Singapore (n=15). This protocol specified analysis included 37 subjects with >12 months post-treatment follow up (median 26.8 months, 95% CI 21.3-32.9). Patient demographics: mean age 52 (range 27 - 84); M:F 31:6; ECOG 0=23, 1=14; stages: T4N1-2 (16), T1-3N3 (18), T4N3 (3). Overall compliance rate: neoadjuvant cisplatin 98.6%, gemcitabine 97.7%, concurrent cisplatin 73.7%, pembrolizumab 100% (neoadjuvant), 77.5% (concurrent), 77% (maintenance), IMRT 99.7% (69.96 Gy). Treatment related adverse events (≥ grade 3, >10%): dysphagia (32.4%), mucositis (29.7%), neutropenia (29.7%), radiation dermatitis (24.3%), anemia (18.9%), hyponatremia (13.5%), thrombocytopenia (10.8%). No ≥ grade 4 mucositis/dermatitis. The 2-yr PFS was 69.6% (95% CI 53.8 - 88.5%). At the end of neoadjuvant, CRT and maintenance phases, molecular remission (pEBV DNA = 0) was achieved in 24.3%, 70.3% and 70.3% of patients respectively, which strongly correlated with PFS (p=0.0253, 0.0007 and <0.0001 respectively, Table). Conclusions: Pembrolizumab incorporated into neoadjuvant, CRT and maintenance protocol is safe with promising results. This strategy of combining ICI with neoadjuvant chemotherapy and CRT is being tested in several ongoing phase 3 trials in advanced NPC. Clinical trial information: NCT03734809 . [Table: see text]
Phase II trial of adjuvant de-escalated radiation + adjuvant nivolumab for intermediate-high risk P16+ oropharynx cancer.
Authors: Skinner Heath Devin , Zandberg Dan Paul , Raben Adam , Sridharan Shaum , Kubik Mark , Zevallos Jose , Kim Seungwon , Duvvuri Umamaheswar , Ohr James , Gooding William E. , Ferris Robert L. 
Published: June 2023

6014 Background: Treatment de-intensification for resected, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is an area of active investigation, with a goal of providing a less toxic adjuvant regimen compared to the current standard of care 66 Gy of radiation (RT) combined with concurrent cisplatin defined in recently reported as Arm D of the ECOG3311 trial. Here, the programmed death 1 (PD-1) antibody nivolumab was added to de-intensified RT in high risk, resected HPV+ OPC. Methods: Eligible patients included transorally resected pathologic stage III or IVA HPV+ OPSCC using p16 immunohistochemistry, featuring high-risk neck disease factors (gross extracapsular extension >1mm or ≥5 positive lymph nodes) to mirror ECOG3311 Arm D patients accrued. Positive margin status was excluded except by PI approval. Postoperative treatment consisted of accelerated fractionation RT (50 Gy over 4 weeks) concurrent with nivolumab at 240 mg every 2 weeks, followed by 6 months of adjuvant nivolumab biweekly or monthly. The primary endpoint was progression-free survival (PFS). Swallowing and quality of life patient reported outcome (PRO) measures were collected at baseline and defined intervals after treatment. Results: Forty-one patients (n=41) were accrued and were analyzed. Forty of 41 patients remain alive with a median follow-up of 30 months (range 1 – 49 months). The probability of 3-year overall survival is 97% (95% CI = 90% - 100%) and the probability of 3-year PFS is 86% (95% CI = 68% - 100%). Two patients developed recurrent disease, one of whom died. One patient developed isolated metastasis while a second developed local, regional, and distant metastasis. The most common adverse grade ≥3 adverse events were lymphocytopenia (n=24), dysphagia (n=2) and oral mucositis (n=2). One grade 4 sepsis/multi-organ failure was reported. Comparison of PRO results with those observed in ECOG3311 trial are underway and will be reported. Conclusions: De-intensification of adjuvant treatment adding nivolumab to RT is tolerable and demonstrates favorable clinical outcome for high-risk, resected, HPV+ HNSCC patients. Further targeted immunotherapy combinations are warranted. Clinical trial information: NCT03715946 .
Nanoparticle albumin-bound (nab) paclitaxel in combination with nivolumab as treatment of recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) that progressed on a PD-1 inhibitor: A single-arm, phase 2 trial.
Authors: Cohen Jared , Oppelt Peter John , Pennock Sarah , Liu Jingxia , Ley Jessica C. , Adkins Douglas 
Published: June 2023

6023 Background: Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, an endocytic nutrient-scavenging process driven by constitutive hyper-activation of the EGFR, RAS, PIK3CA and Syndecan1 signaling pathways that frequently occur in HNSCC. nab-paclitaxel is an active drug in HNSCC and has immunologic effects that can prime an immune response to PD-1 inhibitors, potentially reversing resistance to these agents. These effects include decreased TREGs, increased pro-inflammatory macrophages and differentiation of MDSC to dendritic cells, increased HLA class I expression and antigen presentation, and recruitment of CD8+ CTLs into tumor. Methods: In a single-arm phase 2 trial, patients with RM-HNSCC that progressed on a PD-1 inhibitor received 28-day cycles of nab-paclitaxel (125 mg/m2 IV days 1, 8, and 15) and nivolumab (480 mg IV day 1). Treatment continued until discontinuation criteria were met. The primary endpoint was objective response, assessed with RECIST1.1 by an independent radiologist. The primary hypothesis was that this regimen would result in a higher objective response rate (ORR) than historically reported with standard chemotherapy or cetuximab in similar patients. A Simon optimal two-stage design tested the null hypothesis (H0: ORR≤30%) versus the alternative hypothesis (H1: ORR=50%) at the type I error rate of 5% and power 0.80. In the first stage, 15 patients were to be accrued. If ≥6 responses occurred, 31 additional patients were to be accrued. The null hypothesis will be rejected if ≥19 responses are observed in these 46 patients. We report the results of the primary endpoint for the first stage of the trial. Results: 15 evaluable patients enrolled into the first stage of the trial. Key tumor characteristics and prior treatment history included HPV status (positive: 8; negative: 7), PD-L1 status (CPS 1-19: 7; ≥20: 8), # of lines of prior systemic treatment for RM disease (1-2: 12; ≥3: 3), interval (months) from prior PD-1 inhibitor (<6: 11; ≥6: 4), duration (months) on prior PD-1 inhibitor (median: 6, range: 1-16), and best response to prior PD-1 inhibitor (PR: 4; SD: 6; PD: 5). Tumor response to nab-paclitaxel and nivolumab occurred in 7 of 15 patients (ORR 47%). The best tumor response was PR (7), SD (5) and PD (3). Conclusions: Among patients with RM-HNSCC that progressed on a PD-1 inhibitor, the ORR with nab-paclitaxel and nivolumab was 47% during the first stage of the phase 2 trial. Enrollment to the second stage is ongoing. Clinical trial information: NCT04831320 .
Prognostic value of circulating Epstein-Barr virus DNA level post-induction chemotherapy for patients with nasopharyngeal carcinoma: A recursive partitioning risk stratification analysis.
Authors: Kong Fang-Fang , Pan Guang-Sen , Ni Meng-Shan , Du Cheng-Run , Zhang Zhen , Hu Chaosu , Ying Hong-Mei 
Published: June 2023

6024 Background: To evaluate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level post-induction chemotherapy (IC) for patients with nasopharyngeal carcinoma (NPC). Methods: A total of 893 newly diagnosed NPC patients treated with IC were retrospectively reviewed. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. The receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off value of EBV DNA and compare the predictive validity. Results: Post-IC EBV DNA levels and overall stage were independent predictors for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). The RPA model base on post-IC EBV DNA and overall stage categorized the patients into three distinct risk groups: RPA I (low-risk: stage II-III and post-IC EBV DNA < 200 copies/mL), RPA II (median-risk: stage II-III and post-IC EBV DNA≥200 copies/mL, or stage IVa and post-IC EBV DNA < 200 copies/mL), and RPA III (high-risk: stage IVa and post-IC EBV DNA≥200 copies/mL), with 3-year PFS of 91.1%, 82.6%, and 60.2%, respectively (p < 0.001). The DMFS and OS rates in different RPA groups were also distinct. ROC analysis showed that the RPA model had superior predictive efficacy than the overall stage. Conclusions: Plasma EBV DNA level post-IC was a robust prognostic biomarker for NPC. We developed a risk stratification model that provides improved DMFS, OS, and PFS prediction over the 8th edition of the TNM staging system by integrating the post-IC EBV DNA level and the overall stage.