bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC).
Authors: Wainberg Zev A. , Han Sae-Won , Lee Soohyeon , Lee Keun-Wook , Kopetz Scott , Mizrahi Jonathan , Hong Yong Sang , Ghiringhelli François , Italiano Antoine , Tougeron David , Beagle Brandon , Boakye Mathew , Zhao Tingting , Rhee Joon , Nuyten Dimitry S. A. , Cecchini Michael 
Published: June 2024

3508 Background: Adenosine mediated signaling via A2a and A2b receptors impairs activation, proliferation, and cytotoxic activity of effector T cells resulting in inhibition of antitumor activity. Adenosine receptor blockade may therefore enhance therapeutic efficacy of chemo/immunotherapy regimens. Etrumadenant (E) is an orally bioavailable, selective, A2a and A2b receptor antagonist that has demonstrated safety and clinical activity in solid tumors when combined with chemo/immunotherapy. ARC-9 (NCT04660812), a Phase Ib/II trial evaluating the safety and efficacy of E combined with zimberelimab (Z) (anti-PD-1 antibody), and FOLFOX/bevacizumab (bev) regimens or novel therapies in 3 cohorts of patients (pts) with mCRC. While FOLFOX rechallenge is frequently used in the management of mCRC, no prospective trials have been performed to date. Methods: Cohort B enrolled pts who previously progressed on both oxaliplatin and irinotecan containing regimens.Pts were randomized 2:1 to EZFB: E (150 mg orally [PO] once daily [QD]) + Z (240 mg intravenous [IV] once every 2 weeks [Q2W]) + mFOLFOX-6 + bev (5 mg/kg IV Q2W), or regorafenib (rego) (160 mg PO QD [days 1-21 every 4 weeks]). Pts who progressed on rego were allowed to crossover to EZFB. The primary endpoint is progression-free survival (PFS) per RECIST 1.1 and overall survival (OS) is a key secondary endpoint. Results: In Cohort B, 112 pts were randomized. Baseline characteristics are comparable between arms. As of 13 Nov 2023, with median follow-up of 20.4 months (mo), EZFB demonstrated statistically significant improvement in PFS (HR 0.27, 95% CI 0.17-0.43, p < 0.0001) and OS (HR 0.37, 95% CI 0.22-0.63, p = 0.0003) vs rego (Table). EZFB had an acceptable safety profile, consistent with the known FOLFOX/bev toxicity profile with no deaths related to study treatment in either arm. Conclusions: In this randomized phase II clinical trial, EZFBsignificantlyimproved efficacy outcomes compared to rego in refractory mCRC pts previously treated with 5-FU, oxaliplatin and irinotecan regimens with no unexpected toxicities. Further investigation of this promising regimen is warranted given the clinically meaningful PFS and OS improvement. Table Clinical trial information: NCT04660812 . [Table: see text]
First-in-human study of ABBV-400, a novel c-Met–targeting antibody-drug conjugate, in advanced solid tumors: Results in colorectal cancer.
Authors: Sharma Manish , Strickler John H , Sommerhalder David , Kuboki Yasutoshi , Perets Ruth , Cohen Jonathan , Raimbourg Judith , Nakajima Takako Eguchi , Yamamoto Noboru , Cruz-Correa Marcia , O'Neil Bert , Ghiringhelli François , Raghav Kanwal Pratap Singh , Li Rui , Morrison Thiele Gladys , Neagu Aristide Martha Raluca , Freise Kevin Jay , Biesdorf de Almeida Carla , Vasilopoulos Athanasios , Powderly John D. 
Published: June 2024

3515 Background: c-Met (MET protein) is frequently overexpressed in several advanced solid tumors including colorectal cancer (CRC). There are no approved therapies specific for c-Met–overexpressing tumors in CRC. The antibody-drug conjugate ABBV-400 comprises c-Met–targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. A phase 1 study of ABBV-400 was initiated for adults with advanced solid tumors and progression on standard therapies (NCT05029882); results from dose escalation (ESC) at doses 1.6–6.0 mg/kg once every 3 weeks (Q3W) were previously presented and showed preliminary efficacy (Sharma et al. ASCO 2023. Abstract 3015). We present data from dose ESC and expansion (EXP) cohorts in CRC. Methods: During EXP, patients (pts) with CRC were randomized to receive ABBV-400 at 1.6, 2.4, or 3.0 mg/kg Q3W. Primary objectives were to evaluate the safety, tolerability, pharmacokinetics, preliminary efficacy, and the recommended phase 2 dose of ABBV-400. Results: As of Oct 2023, 122 pts (ESC: 29; EXP: 93) were included. Median age: 56 years; 65 (53%) males. Median prior treatments was 4. Follow-up was longer in ESC vs EXP (14.8 vs 3.8 months). Seventy-eight (64%) pts had a grade (G)≥3 treatment-emergent adverse event (TEAE); 41% had a serious TEAE. Most frequent hematologic TEAEs were anemia (52%; G≥3: 30%), neutropenia (37%; G≥3: 25%), leukopenia (25%; G≥3: 12%), and thrombocytopenia (23%; G≥3: 12%); nonhematologic TEAEs were nausea (57%, G≥3: 3%), fatigue (43%; G≥3: 2%), and vomiting (39%, G≥3: 4%). G≥3 diarrhea was < 1%. Unadjudicated interstitial lung disease/pneumonitis rate was 7% (G≥3: 2%). Treatment-related AEs leading to discontinuation occurred in 11 (9%) pts. Preliminary efficacy outcomes are shown in the Table. The majority of tissues expressed c-Met. In pts with higher c-Met expression, an increased ORR of > 30% was observed at efficacious doses (≥2.4 mg/kg). Activity was also seen at lower c-Met expression levels (10–15% ORR). Conclusions: ABBV-400 at 2.4 and 3.0 mg/kg Q3W has a tolerable and manageable safety profile, with promising antitumor activity. Long-term tolerability appears improved at 2.4 relative to 3.0 mg/kg, with higher relative dose intensity and generally lower TEAEs. The study is also evaluating ABBV-400 with bevacizumab in pts with CRC. Clinical trial information: NCT05029882 . [Table: see text]
Three-year disease-free survival after transanal vs. laparoscopic total mesorectal excision for rectal cancer (TaLaR): A randomized clinical trial.
Authors: Kang Liang , Zeng Ziwei , Liu Huashan ,   Chinese Transanal Endoscopic Surgery Collaborative (CTESC) Group
Published: June 2024

3516 Background: Transanal total mesorectal excision (taTME) has gained significant traction as an effective approach for treating rectal cancer. Many previous studies reported positive relevant short-term results, histopathological results and associated complications of taTME compared to laparoscopic total mesorectal excision (laTME). Nonetheless, long-term oncological outcomes of taTME remain controversial. This study aimed to compare the 3-year DFS of taTME with laTME. Methods: We conducted a phase 3, randomized, open-label, noninferiority trial to compare the survival outcomes of taTME versus laTME in patients with rectal cancer located below the peritoneal reflection. This trial encompassed 16 hospitals across 10 provinces in China, with a total enrollment of 1,115 patients. We set the 3-year disease-free survival (DFS) and 5-year overall survival (OS) as the primary endpoints for analysis. The analysis of the 3-year DFS was conducted following a predefined modified intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02966483. Results: The taTME group exhibited a 3-year DFS rate of 83.42%, and the laTME group achieved a 3-year DFS rate of 82.86%. The marginal difference of 0.56% between the DFS rates of the two groups (97.5% CI, −4.83 to 5.95, P < 0.0001 for noninferiority) suggests comparable outcomes. Moreover, the rates of local recurrence were 3.90% in the taTME group and 3.62% in the laTME group, indicating similar degrees of localized tumor control. Regarding overall survival, the taTME group demonstrated a rate of 94.50% compared to 92.01% in the laTME group. In the taTME group, patients who are male or underwent neoadjuvant showed a higher 3-year OS than that in the laTME group. Conclusions: In patients with mid-low rectal cancer, the 3-year DFS of taTME is not inferior to that of laTME. This study provides evidence supporting the clinical effectiveness of taTME in the treatment of rectal cancer. Clinical trial information: NCT02966483 .
Factors associated with benefit of adjuvant chemotherapy in patients with T1b/T1c HR-positive/HER2-negative breast cancer and high multigene recurrence score.
Authors: Herran Maria , Sabbagh Saad , Hijazi Ali , Mohanna Mohamed , Sarna Kaylee , Dominguez Barbara , Nahleh Zeina A. 
Published: June 2024

e12540 Background: Patients diagnosed with early-stage HR-positive/HER2-negative Breast Cancer (BC) and high Oncotype DX Recurrence Score (RS ≥26) are offered adjuvant chemotherapy and endocrine therapy compared (CET) to endocrine therapy alone (ET). We sought to investigate if additional clinical factors that could further determine benefit from chemotherapy in patients with T1b/T1c and N0 tumors with high Oncotype DX to help deescalate treatment by avoiding chemotherapy induced toxicity. Methods: The purpose of this study is to determine the clinical factors associated with a survival difference from CET compared to ET alone in T1b/T1c and N0 BC. We analyzed the record of patients diagnosed with T1b/T1cN0M0 HR-positive/HER2-negativeBC and RS ≥26 between 2006 and 2020 from the National Cancer Database. Patients were separated into two groups based on their treatment: CET or ET and the following characteristics were assessed: age, grade, histology, and RS (26-30, 31-40, 41-100) to determine overall survival differences among the two groups. Chi-square was performed to evaluate the association between baseline categorical characteristic variable and chemotherapy treatment. Survival analysis of treatment modalities using Kaplan Meier curves and univariate Cox regression. Multivariate Cox regression with backwards elimination was performed for subgroup analyses. Results: A total of N=19,373 eligible patients were identified, n=14,422 (74.4%) received CET and the rest ET alone. The mean age at diagnosis was 59.6 years (SD=10.3); 86.6% presented with invasive ductal carcinoma and 83.3% had a Charlson-Deyo Comorbidity Score of 0. In the overall group, patients who received CET had a higher median overall survival than endocrine therapy alone (65.7 versus 52.1 months, log-rank p-value<.0001). However, further analysis noted that treatment with CET showed better outcome compared to ET alone in the following subgroups of patients: invasive ductal histology (95% OS 65.5 versus 52.7 months, log-rank p-value<.0001) and RS >30 (95% OS 63.6 versus 40.5 months, log-rank p-value<.0001). Importantly, multivariable cox regression subgroup analysis revealed no significant overall survival difference among the subgroup of patients with T1b/T1c and low grade (p=0.286) or RS 26-30 (p=0.200) with CET compared to ET alone. Conclusions: This large database confirms the heterogeneity of BC in patients with low burden disease despite high Oncotype.While patients diagnosed with T1b/T1cN0M0 and high RS (>30) could benefit from CET compared to ET alone as per standard practice, additional criteria could be considered in this group including low grade or RS 26-30 to better determine which population of patients do not benefit from the addition of chemotherapy and accordingly individualized chemotherapy decision might be made to minimize toxicity.
PRE-ISPY phase I/Ib oncology platform program (PRE-I-SPY-P1).
Authors: Pohlmann Paula R , Potter David Alexander , Chen Nan , Mouabbi Jason A , Rampurwala Murtuza , Rayani Shayan , Tan Antoinette R. , Leon-Ferre Roberto Antonio , Giridhar Karthik , Boughey Judy Caroline , Han Hyo S. , Kennedy Laura Carpin , Walsh Elaine M. , Tripathy Debashish , Jafari Shabnam , Eklund Martin , Nanda Rita , Meric-Bernstam Funda , Yee Douglas , Esserman Laura 
Published: June 2024

e12641 Background: Many promising agents or combinations regimens relevant to breast cancer lack sufficient clinical information for use in the neoadjuvant setting. To enable acceleration of drug development by reducing time and cost of clinical trial planning and conduct, the Phase I initiative PRE-ISPY Program was created. Methods: The PRE-ISPY Program is built within the I-SPY network, with the overall aim to streamline the regulatory pathway and the processes of trial design, contracting, activation, enrollment, execution, data gathering and analysis, as well as reporting of new therapeutic agents or combinations of relevance to breast cancer. Results: The PRE-ISPY trial is an open-label platform phase IB study designed to evaluate compelling single agent or combination regimens with the overall goal of moving promising drug regimens into I-SPY2 Trial and/or into other oncology-based trials in a timely manner. Graduation of a PRE-ISPY regimen to I-SPY2 is not mandatory. The primary objectives in each study Arm are to determine safety and to obtain preliminary efficacy data of the new regimen in patients with metastatic cancer, including a cohort of breast cancer patients. Each Arm may contain a Part 1 (dose finding) and a Part 2 (dose expansion). The new treatment can be tested also in patients with other solid malignancies than breast cancer, in which the treatment may be applicable, as specified in the design of the Arm. A breast cancer specific cohort is required in Part 2. Candidate treatment regimens are selected with advice from the I-SPY2 Agent Selection Working Group. The PRE-ISPY/Phase IB trial has multiple ongoing drug regimen Arms subsequently added as new protocol appendices through amendments to a Master protocol. There is no randomization; participants are enrolled, and treatment selected according to the relevance of therapy to their disease. Prospective companion biomarkers are evaluated. The current arms under study are PRE1: ALX-148 combined with trastuzumab deruxtecan; PRE2: tucatinib combined with zanidatamab; and PRE3: vidutolimod combined with cemiplimab. Selected agents or therapeutic combinations are tested through this protocol in the I-SPY Network Centers that participate in the PRE-ISPY Program. Toxicities are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Clinical responses are evaluated based on RECIST v1.1 criteria. Conclusions: Once safety is established, promising regimens can be rapidly transitioned to I-SPY 2.2 or other phase 2/3 trials. The first patient was enrolled on 2/1/2023. Clinical trial information: NCT05868226 .
Efficacy and safety of dalpiciclib, fulvestrant, and pyrotinib in HR+ HER2-low advanced breast cancer following cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors and aromatase inhibitors (AIs): A Bayesian optimal phase II trial.
Authors: Hao Chunfang , Shi Jing , Zhang Jie , Meng Wenjing 
Published: June 2024

e13056 Background: Cross-line treatment with CDK4/6 inhibitors is a challenging topic. Currently, the MAINTAIN study, which involves switching CDK4/6 inhibitors and endocrine therapy, is the only one with positive results. Additionally, in vitro studies have demonstrated that the combination of anti-HER2 agents with CDK4/6 inhibitors, along with fulvestrant, can synergistically enhance inhibition in cell lines with low HER2 expression. The present study aims to assess the efficacy and safety of dalpiciclib, fulvestrant, and pyrotinib in patients with HR-positive and HER2-low advanced breast cancer (BC), who have experienced disease progression after treatment with CDK4/6 inhibitors and AIs. Methods: We propose a single-arm Bayesian optimal phase II design with a time-to-event endpoint. Key eligibility criteria include patients over 18 years of age with HR+, HER2-low advanced BC, disease progression following treatment with CDK4/6 inhibitors and AIs, no more than one line of chemotherapy. Patients who meet these criteria will receive oral dalpiciclib at a dose of 125 mg/day (three weeks on and one week off), intramuscular fulvestrant at a dose of 500 mg every four weeks, and oral pyrotinib at a dose of 320 mg/day until intolerance or disease progression. The primary endpoint of the study is progression-free survival (PFS), and the secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival, safety, and biomarker analysis. The study aims to enroll up to 30 patients, and an interim analysis will be conducted after the enrollment of 15 patients to make a go/no-go decision based on the stopping boundaries of the total observation time (TOT). Results: From May 2023 to November 2023, a total of 15 patients were enrolled in the study. The median age of the patients was 50 years (range: 36-72). Among these patients, 7 (46.7%) had visceral metastasis, 11 (73.3%) had undergone previous chemotherapy, 12 (80.0%) received abemaciclib, and 3 (20%) received palbociclib. The median duration of prior treatment with CDK4/6 inhibitors was 14 months (range: 5-33). As of January 24, 2024, a total of 9 patients underwent efficacy evaluation, revealing an ORR of 44.44% (4/9) and a DCR of 66.67% (6/9), 4 patients experienced disease progression. The TOT was 49.50 months, exceeding the predetermined stopping boundary of 22.54 months. Currently, the survival data are immature. The median follow-up period is 3.20 months (95% CI: 2.33-NA), and the median PFS has not been reached. Grade 3 and above treatment-related adverse events were reported in 40% (6/15) of the patients. Conclusions: The preliminary results indicate a certain level of efficacy and manageable safety. Based on these findings, the study will continue to enroll up to 30 participants. Clinical trial information: NCT05806671 .
Results of a retrospective study on the efficacy and safety of alpelisib in patients with HR+/HER2- metastatic breast cancer in real-world clinical practice.
Authors: Sultanbaev Alexander Valerievich , Kolyadina Irina Vladimirovna , Menshikov Konstantin , Musin Shamil , Sultanbaeva Nadezda , Lipatov Danila 
Published: June 2024

e13058 Background: The combination of alpelisib and fulvestrant is an optimal therapy option for patients with hormone receptor-positive (HR+), HER2-negative (HER2–) metastatic breast cancer with PIK3CA gene mutations. The aim of this work to retrospectively analyze the efficacy and safety of alpelisib in real-world clinical practice in patients with pre-treated luminal HER2– negative metastatic breast cancer. Methods: The study included an analysis of 33 patients with widespread luminal HER2- negative breast cancer with detected PIK3CA gene mutation. The median age was 57 ± 13 months (95% CI 52-62). In 12 (36.4%) patients, the PIK3CA gene mutation was detected in exon 9, and in 21 (63.6%) – in exon 20. Alpelisib was prescribed to pre-treated patients in different lines. Most women (32/33; 97%) had received ET combined regimens with CDK4/6 inhibitors before starting alpelisib therapy: 14 (42.4%) patients underwent palbociclib therapy in combination with fulvestrant; 4 (12.1%) – palbociclib with aromatase inhibitors; 13 (39.5%) – ribociclib in combination with fulvestrant; 1 (3.0%) – ribociclib with aromatase inhibitors. It is important to note that 63.6% of patients had previous progression on fulvestrant monotherapy and 72.7% on aromatase inhibitor therapy. Patients with luminal B-subtype of breast cancer dominated - 72.7% (24/33). Results: The median overall survival (OS) in this study was 14 ± 2.5 months (95% CI: 9-18.9), and the median progression-free survival (PFS) was 6 ± 2.7 months (95% CI: 0.7-11.3). The rate of objective response was 30.3%, and prolonged disease stabilization was observed in 24.2% of cases. Prognostic factors were brain metastases (increasing the risk of death by 18 times) and discontinuation of the drug for any reason (increasing the risk of death by 8 times). It should be noted that the main reason for discontinuation or disruption of the drug's timing was unmanageable toxicity. All patients registered adverse events of varying degrees, with 21 (63.6%) patients experiencing hyperglycemia (grade 3-4 – 30.3%) and 14 (42.4%) patients experiencing skin toxicity (grade 3-4 – 15.2%). In the SOLAR-1 study, the frequency of hyperglycemia was comparable (64.8%), and rash was noted in a third of all patients, which is comparable to our data. Conclusions: The results of using alpelisib with fulvestrant confirm its effectiveness in real-world clinical practice in patients with pre-treated HR+HER2- negative widespread breast cancer with the presence of somatic PIK3CA gene mutation. Brain involvement is an unfavorable prognostic factor in patients with PIK3CA mutation and increases the risk of death by 18 times, requiring the need to optimize the therapeutic algorithm, including through radiation methods. Discontinuation of the drug, which increases the risk of death by 8 times.
Acceptance and usability testing of a visual care-navigation tool for patients, survivors, caregivers, nurses, and oncologists.
Authors: Daswani Samira , Blayney Douglas W. , Lindquist Molly , Dasgupta Arko , Finley Stephanie , Leung Celeste 
Published: June 2024

e13064 Background: Breast cancer patients (BCP) and family caregivers (CG) describe their experience as a difficult hike, without access to a map, relevant gear, or a guide. The shrinking oncologist workforce has ~24 minutes per patient to communicate the condition, treatment plan and answer questions. Many use hand-drawn visuals – analogous to a map or process flow diagrams. 97% of BCP use Dr. Google™, which results in “Cancer Information Overload” and non-evidence-based activities. A team of survivors, cartographers, and oncologists developed an interactive cancer map and self-management platform to coach BCP to navigate treatment. Using equitable design, features include: (a) 7th grade reading level; (b) written content and audio/video assets; (c) supporting the user from diagnosis through survivorship to make the platform accessible to a diverse population. After acceptance testing showed high willingness to use & recommend (ASCO Quality 2023;552), we tested the platform’s usability through observed use and task-analysis. Methods: A convenience sample of BCP, CG and oncology HCP [including advanced practice providers (APP)] underwent a usability test in two waves. We defined a set of tasks the users should be able to accomplish. We observed the users during a 30-minute virtual session and recorded the session, noted the task accomplishments, and any issues. Issues from wave 1 were addressed and incorporated into the test for wave 2. Results: We tested two waves of users between November 30, 2023 and February 1, 2024. The results are shown in the table. After wave 1, we modified the platform and tested the maps with wave 2 users. Two core usability features were added between waves: (a) user drill down to access a more detailed level of the map; (b) a product tour guiding the user through the tool, which addressed qualitative user observations that showed initial confusion as to how to begin navigation. Conclusions: Cartographically represented maps of the cancer journey and the self-management tools are acceptable to BCP, survivors, and CG and are usable. Per the ASCO Quality 2023;552 poster, the platform is acceptable to HCPs and not perceived to increase work, and APPs found value in the platform to enable education. Features have been added to ensure a diverse population can easily use the platform including guided walk through and welcome videos. [Table: see text]