tbuckley/cabot-search huggingface dataset:
LOOP: An observational, prospective, multicenter study of patients with non-small cell lung cancer in the US receiving standard-of-care and initiating an approved therapy with risk of pneumonitis/ILD.
Authors: Elisabeth C Piault-Louis, Melissa Marvel, Michael David Newton, Vincent Haddad, Emmette R Hutchison, Joseph T Hughes, Alicyn K Campbell, Ethan Basch
Journal: Journal of Clinical Oncology (2024)

TPS12157 Background: A wide range of oncology treatments are associated with a risk of pneumonitis or ILD, which is an uncommon but serious side effect with potential for significant morbidity and mortality (Conte et al 2022). The development of pneumonitis/ILD remains unpredictable and relatively uncommon in a single practice or hospital setting. Risk of drug-induced pneumonitis/ILD remains a limiting factor to prescribing life-saving treatments. A non-invasive, patient-centric multimodal solution for remote data capture could support recognition and tracking of pulmonary symptoms in addition to providing insight for the clinical team to personalize the monitoring of patients according to their medical history or specific physiological markers. Methods: LOOP is an observational, prospective, multicenter study conducted in the US. Stage III and IV NSCLC patients receiving SoC and initiating treatment with an FDA-approved ICI (alone or in combination with other agents), ADC, or small molecule EGFR inhibitor are eligible to participate. The primary objective is to enable the development and refinement of an algorithm including documentation of its performance (specificity, sensitivity and odd ratio to inform risk of pulmonary/respiratory/thoracic-related events including ILD). A secondary objective proposes to characterize the risk factors, signs, and symptoms leading to onset, diagnosis, and treatment of pneumonitis/ILD in patients receiving SoC. The study will collect patient-generated data outside of point-of-care for six months, using questionnaires and a medical pulse-oximeter device . Clinical data available per SoC in the medical records will be collected. Approximately 600 patients will be enrolled over 13 months to accrue approximately 100 pneumonitis/ILD events. Events will include all grades of pneumonitis, including ILD and radiation pneumonitis, as determined by the Investigator. Qualitative interviews will be conducted to inform a more granular understanding of the patient specific experience of developing ILD. Logistic regression, area under curve, descriptive statistics and relevant visualizations will map the relationship between pneumonitis/ILD and patient’s health status. The study is currently enrolling; the protocol was approved by a central IRB. Clinical trial information: NCT06192004 .
Quantifying the risk of hypocalcemia in individuals treated with cabozantinib.
Authors: Anirudh Murthy
Journal: Journal of Clinical Oncology (2024)

e24110 Background: Cabozantinib, a potent inhibitor for multiple receptor-tyrosine kinases, has been approved for the treatment of various advanced cancers. The risks of all-grade and high-grade hypocalcemia have been noted in many clinical trials. We have conducted an up-to-date systematic review and meta-analysis of clinical trials using single agent cabozantinib to assess the overall risk of hypocalcemia. Methods: We systematically identified relevant English-language studies primarily from PubMed and Clinicaltrials.gov (up to March 2023), covering phase I to phase III trials using cabozantinib in cancer patients. Studies with patients assigned to single agent cabozantinib with available data on hypocalcemia were included. We employed fixed-effects or random-effect models depending on study heterogeneity to calculate the incidence and relative risk of hypocalcemia. Results: A total of nineteen studies were included for analysis. The overall incidence of all-grade hypocalcemia with cabozantinib was 15.0% (95% CI: 9.0-21.0%), with a high-grade (grade 3 or 4) incidence of 2.0% (95% CI: 1.0-3.0%). Significant variability was observed among different tumor types (p &lt; 0.001), ranging from 45.0% in multiple myeloma to 2.0% in hepatocellular carcinoma and colorectal cancer. In comparison with placebo, cabozantinib significantly increased the risk of hypocalcemia with an RR of 1.75 (95% CI: 0.96-2.53, p &lt; 0.001). However, when compared to prednisone, cabozantinib showed a non-significant risk reduction of 0.30 (95% CI: -0.20-0.79, p = 0.24). Furthermore, cabozantinib did not elevate the risk of hypocalcemia compared to other chemotherapeutic agents (everolimus, paclitaxel, and sunitinib). Conclusions: Patients undergoing cabozantinib treatment face an increased risk of hypocalcemia, with variations observed across different tumor types. Proactive measures can be implemented to prevent or mitigate hypocalcemia during cabozantinib therapy. Additionally, monitoring vulnerable patient populations is essential to optimize clinical care and enhance overall outcomes.
Real world data of safety of immune-checkpoint inhibitors in patient with cancer at tertiary care hospital in Saudi Arabia.
Authors: Ahmed Alanazi, Iman Alzaharani, Mohammed Salman Bashir, Fouad H. AlNajjar
Journal: Journal of Clinical Oncology (2024)

e24104 Background: Immune checkpoint inhibitors (ICIs) become an integral part of many cancer therapies, such as melanoma, esophageal carcinoma, breast cancer and other malignancies. Immune checkpoint inhibitors work by activation the immune system that blocks negative regulators expressed on immune or tumor cells. Accordingly, the mechanism of action of ICI may cause autoimmunity-like symptoms called immune-related adverse events (irAEs) that affect many organs in body like skin, liver, lung, endocrine and gastrointestinal tract. These irAEs may reduce the organ function, quality of life and it may cause death. The present work addressed the knowledge gap in understanding real-world outcomes of irAEs associated with ICIs. Real-world patients are more diverse than clinical trial. Methods: This retrospective cohort study investigated the use of immune checkpoint inhibitor (ICI) therapy in an oncology and hematology patients treated at King Fahad Medical City (KFMC) comprehensive cancer center between February 2021 and February 2023. Adult patients (≥ 18 years old) diagnosed with any malignancy or hematological disorder who received at least one dose of ICI therapy during the study period have been included. Patients younger than 18 years old have been excluded. Demographic, clinical, and treatment data have been extracted from the electronic medical records (EMR). The study protocol has been reviewed and approved by the KFMC Institutional Review Board (IRB). The trial still undergoing not yet finished. Results: A total of 44 patients were included by the time preliminary data analysis was conducted on January 1st, 2024. All Patient included were receiving Pembrolizumab 44 patients. In regards to demographics, 27 (61.4%) of the patients were female. Breast cancer was the most common diagnosis (34.1%), followed by non-small cell lung cancer (22.7%). Among patients undergoing ICI, 34.1% had at least one Emergency Room (ER) visit. Notably, 25% of these patients had 1-2 ER visits. The most common reason for ER visits was patient complaints of GI toxicity related to ICI, including nausea, vomiting, and diarrhea (colitis). 12 (26.8%) patients required hospitalization, and 9 (20.5%) stayed for more than seven days.The time to first adverse event of ICI therapy was most commonly seen after nine weeks in 8 (18.2%) patients. Hypothyroidism was the most common adverse event (11.4%), followed by gastrointestinal toxicity (6.8%). Skin, grade 2 hepatotoxicity, and renal toxicity were also reported in 1 (2.3%) patient respectively. Conclusions: Overall, this initial analysis suggests that while ICI known to offers promising potential, it also carries the risk of various adverse events, including a significant rate of ER visits and hospitalizations. Further investigation with larger patient cohorts is warranted to confirm these findings and optimize IO therapy management.
Comparison of prophylactic effects for chemotherapy-induced neutropenia between same-day vs next-day administration of pegteograstim in chemotherapy regimen composed of day 1 intensive myelosuppressive agent: A randomized phase III trial (CONCISE, KCSG PC22-11).
Authors: Kwonoh Park, Sang-Bo Oh, Yun Jeong Hong, Seok Jae Huh, Il-Hwan Kim, Seong-Hoon Shin
Journal: Journal of Clinical Oncology (2024)

TPS12149 Background: Administration of peg-GCSF 24 to 72 hours after chemotherapy is usually recommended. Next-day administration (after 24 hours) resulted in fewer duration of Gr4 chemotherapy-induced neutropenia (CIN) and decreased severity of CIN than same-day (within 4 hours). However, patients sometimes receive same-day Peg-GCSF for the sake of convenience. In addition, a few prior studies showed that the same-day method is comparable or superior to the next-day in preventing CIN, especially in regimens that include day 1 myelosuppressive agents. Thus, we aim to test hypothesis that same-day administration of pegteograstim, a new formulation of peg-GCSF, is non-inferior to next-day administration in terms of Gr4 CIN duration. Methods: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients with adjuvant/neoadjuvant or 1st palliative chemotherapy comprising intensively myleosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled. The patients are assigned to the same-day arm or the next-day arm in a 1:1 ratio. Randomizations are stratified according to number of CIN risk (1 vs ≥2), setting (perioperative vs palliative), and interval (2- vs 3-week). In the same-day, pegteograstim 6 mg is SC injected within 4 hrs after chemotherapy, while 24-36 hrs in the next-day. CBC test is performed daily from day 5 to 9 during the cycle 1. From cycle 2 to 4, treatments are performed in accordance with general practice, including checking for febrile neutropenia (FN), dose intensity, and safety. The primary endpoint is duration of Gr4 CIN (during cycle 1), and secondary endpoints include incidence of Gr 3-4 CIN (cycle 1), severity of CIN (cycle 1), time to recovery ANC 1000/㎕ (cycle 1), incidence of FN, CIN-related dose delay, and dose intensity. In order to verify non-inferiority of 0.6 days of Gr4 CIN duration, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each arm. We are currently recruiting patients (since Nov 2022). Clinical trial information: KCT0007694 .
Acupuncture for preventing progression of taxane-induced peripheral neuropathy (ATP): A phase II randomized, placebo-controlled trial.
Authors: Iris Zhi, Katherine Han, Danne Kim, Lauren Piluson, Matthew Weitzman, Raymond E Baser, Qing Susan Li, Ting Bao, Jun J. Mao
Journal: Journal of Clinical Oncology (2024)

TPS12154 Background: Chemotherapy-induced peripheral neuropathy (CIPN) from chemotherapy drugs such as taxanes can be detrimental to cancer survival, increasing the risk of falls and worsening physical functions. The current management of worsening and persistent CIPN during chemotherapy is dose reduction or discontinuation of chemotherapy. There is no effective treatment or preventative measure for CIPN. Methods: Trial design: The ATP trial is a two-arm, parallel, randomized controlled trial comparing weekly real acupuncture (RA) versus sham acupuncture (SA) during preplanned curative intent taxane containing regimens in patients with breast cancer. Eligibility criteria: English or Spanish-proficient; aged ≥18 years; histological diagnoses of invasive carcinoma of the breast; and plan to receive curative intent chemotherapy regimen containing paclitaxel or nab-paclitaxel weekly or biweekly as standard of care, developed CIPN grade ≥1 based on the NCI-CTCAE version 5.0, while receiving taxane; ≥ four weeks of paclitaxel or nab-paclitaxel weekly or biweekly planned, as standard of care and at treating physician’s discretion; willing to adhere to requirement that no new pain medication or dose changes be taken throughout the first 12 weeks of the study period; and willing to adhere to all study-related procedures. Specific aims: The primary aim is to evaluate the effectiveness of RA versus SA in preventing taxane-induced peripheral neuropathy progression as measured by Neuropathic Pain Scale (NPS) in patients with early-stage breast cancer who are receiving curative intent neurotoxic chemotherapy. The secondary aim is to evaluate the effectiveness of RA versus SA on chemotherapy relative dose intensity (RDI) and CIPN-related chemotherapy discontinuation. Statistical methods: We will randomize 80 patients, 40 to each arm. All randomized patients will be evaluable in the Intent to Treat (ITT) analyses because all will have completed the baseline assessment before randomization. We will use a linear mixed model (LMM) to compare the change in NPS between the arms from baseline to week 4. Based on our pilot data, a difference in CIPN grade from 1 to 2 corresponded to a difference in NPS from 12 to 22, a difference of ten points in 27 patients. The NPS standard deviation (SD) in patients with grade 1 CIPN was 17. With 80 patients we will have 80% power to detect a difference between arms as small as 10 points on the NPS, assuming a one-sided test, type I error of 5%, correlation between baseline and follow-up measurements of 0.5, SD of 17, and 15% attrition at week 4. Present accrual and target accrual: We accrued 43 participants in the intervention phase by the end of January 2024; the target accrual is 80 participants. Clinical trial information: NCT05458284 .
DEFENDOR: Real-world evidence of primary prolonged G-CSF prophylaxis by empegfilgrastim for relative dose intensity compliance in patients with solid tumors—The final analysis.
Authors: Anton Snegovoy, Inessa Kononenko, Irina Radyukova, Svetlana Orlova, Tatiyana Starostina, Alexander Valerievich Sultanbaev, Daria Dubovichenko, Alexander Dergunov, Alexandra Saydullaeva, Nadezhda Repina, Yulia Gronskaya, Elena Rossokha, Irina Sorokina, Oksana Prosianikova
Journal: Journal of Clinical Oncology (2024)

e24109 Background: Myelosuppression management under chemotherapy (CT) is crucial for maintaining the relative dose intensity (RDI) of therapy and ensuring effective treatment of patients with solid tumors (ST). RDI &gt; 85% is associated with better overall survival for the most ST. Granulocyte colony stimulating factors (G-CSF) have been the standard of care for the prevention of chemotherapy-induced neutropenia (CIN). Here we present the final results of a multicenter prospective observational post-marketing study of safety and efficacy of pegylated G-CSF Extimia (INN: empegfilgrastim, JSC BIOCAD) in pts with ST who receive cytotoxic therapy. Methods: The primary endpoint was the RDI of CT courses (4-8 cycles per course are allowed) with empegfilgrastim support. RDI was calculated for each single agent in the chemotherapy-based (CTb) regimen and for the CTb regimen in total. Extimia (7,5 mg) was administered subcutaneously once per chemotherapy cycle. Results: The study included 3218 pts with various tumor types across 41 centers in Russia. 3217 (99.97%) pts received at least one dose of the study drug. 2663 (82.8%) pts were included in the RDI assessment population per protocol. The average age of pts was 56.9 (18–84) y.o. Individuals aged ≥65 y.o accounted for almost one third of all pts. RDI ≥ 85% was achieved in 2415 (90.7%) pts (Table 1). 1447 (54.3%) pts have at least one FN risk factor whereas age ≥ 65 years is the most common (763/2663 (28.6%) pts). 91.5% RDI was registered in pts &lt; 65 y.o and 88.7% RDI - in pts ≥ 65 y.o. Neutropenia was reported in 19 (0.7%) cases as a reason of RDI decrease. Grade 3-4 AEs were recorded in 74 (1.8%) cases in 59 pts whereas neutropenia (n = 22), anemia (n = 8) and diarrhea (n = 6) were the most common (CTCAE (v. 5.0)). Conclusions: Primary prolonged G-CSF prophylaxis by empegfilgrastim allows effectively maintaining RDI across various tumor types (TT) and treatment groups in pts with ST in routine clinical practice. Clinical trial information: NCT0481144 . [Table: see text]
A single-center retrospective review of the impact of cryotherapy on peripheral neuropathy scores in patients with breast cancer who received chemotherapy with a taxane-based treatment regimen.
Authors: Deanna Huffman, Austin Primeaux, Elizabeth Reilly Helm, Lily Zhiying Chen, Joseph Mason, Rafael Guzman-Arevalo, Andrew G Chapple, Michelle Marie Loch
Journal: Journal of Clinical Oncology (2024)

e24106 Background: Taxanes are a class of chemotherapy frequently used for neoadjuvant and adjuvant treatment of breast cancer. While effective, taxane use is not without adverse effects, the most well-known being chemotherapy-induced peripheral neuropathy (CIPN). As CIPN is dose-related, it can lead to dose reductions and interruptions in therapy that may be detrimental to the patient. Cryotherapy has been used as a prevention strategy, but its efficacy remains unclear. Methods: We performed a retrospective review of the cryotherapy program in our center. Included patients had breast cancer of any stage treated with a taxane in the neoadjuvant or adjuvant setting. All patients were offered cryotherapy at the time of their treatment and were separated into cohorts whether they opted in or out (“cryotherapy” and “non cryotherapy,” respectively). Neuropathy scores were collected by nursing staff via survey and scaled from 0-4. Patient demographics and neuropathy scoring were compared between the “cryotherapy” and “non cryotherapy” cohorts. Results: In total, 41 patients were included. Nearly half of patients in each cohort experienced neuropathy, 10 patients (41.7%) treated with cryotherapy and 8 patients (47.1%) without cryotherapy use. Younger age (46.5 years vs 57 years, p = 0.060), and patients using Medicaid (35.3% vs 75.0%, when compared to all other insurance types, p = 0.023) predicted cryotherapy use. Use of paclitaxel also predicted cryotherapy used when compared to docetaxel (76.0% and 31.2%, respectively, p = 0.009). There was not a significant difference in predicted neuropathy score between the cohorts (Adjusted Multiplicative Effect = .81, 95% CI = .34-1.96, p = .645). Conclusions: Our data did not suggest that the use of cryotherapy could predict lower neuropathy scores, but our study suffered from small sample size and short-duration of follow-up. Additional large, randomized trials with standard neuropathy scoring scales are needed to better evaluate the efficacy of cryotherapy in prevention of CIPN for breast cancer patients receiving taxane-based therapy.
Response by van Doorn et al to Letters Regarding Article, “Safety of Switching From a Vitamin K Antagonist to a Non–Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial”
Authors: Sander van Doorn, Frans H. Rutten, Geert-Jan Geersing
Journal: Circulation (2024)
The CROWN study: Cardiac outcomes with near-complete estrogen deprivation.
Authors: Rani Bansal, Emily H. Douglas, Katherine C. Ansley, Carolyn J. Park, Karl M. Richardson, Susan Faye Dent, Carey K. Anders, Kelly E. Westbrook, Mary Helen Helen Hackney, Hetal Ravikumar Vachhani, Elizabeth Barrows, Sarah Hatcher, Ralph D'Agostino, Jennifer Jordan, Alexandra Thomas
Journal: Journal of Clinical Oncology (2024)

TPS12146 Background: Treatment for premenopausal women with high/intermediate risk hormone receptor (HR)-positive breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near-complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV morbidity. Given the overall CV injury associated with BC treatment and the future life-years of these women, the CV impact of NCED warrants further study. The CROWN study uses sophisticated imaging assessments of cardiac dysfunction and biomarker and demographic correlates to understand the evolution of CV injury with the goal of developing tools to assess and mitigate CV risk. Methods: This is an NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Duke University, Wake Forest University and Virginia Commonwealth University) that includes premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-2. HR-positive BC patients are receiving an AI and OFS. Women with HR-negative BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table). These assessments include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. Correlation of CMR imaging with CCTA detail of coronary plaque changes is planned. The relevance of pre-existing risk factors on study outcomes, including an emphasis on race and dynamic change in modifiable and treatment related risk factors will also be assessed. We plan to enroll 90 women,65 in the NCED group and 25 in the HR-negative group, allowing for a 10% drop out rate. The first primary statistical analyses will include testing hypotheses between group (NCED vs HR-negative) and within group (longitudinal changes within the NCED group). Secondary analyses involve developing predictive equations to determine if patient demographics, clinical parameters and serum biomarkers are associated with CV changes over time. We have currently enrolled 34 women (31 NCED and 3 HR-negative). 2 out of 3 patients entering the 2 nd year of the study have returned for their year 1 imaging. Retention will be a key component of this study as analysis of the primary and secondary endpoints are dependent on completion of imaging. Clinical trial information: NCT05309655 . [Table: see text]
Letter by Ko et al Regarding Article, “Safety of Switching From a Vitamin K Antagonist to a Non–Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial”
Authors: Darae Ko, Dae Hyun Kim, Daniel E. Singer
Journal: Circulation (2024)