tbuckley/cabot-search huggingface dataset:
Anlotinib plus sintilimab in patients with recurrent advanced cervical cancer: A prospective, multicenter, single-arm, phase II clinical trial.
Authors: Qin Xu, Chuanben Chen, Yang Sun, Zhangzhou Huang, Yibin Lin, Jing Liu, Li Li, Zirong Li, Junping Pan, Ying Chen
Journal: Journal of Clinical Oncology (2021)

5524 Background: It is difficult for patients with recurrent advanced cervical cancer to obtain clinical benefits after the failure of standard chemotherapy. However, antiangiogenic therapy combined with immune checkpoint inhibitors have become a promising strategy for advanced cervical cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. Sintilimab is a fully humanized, high-affinity monoclonal antibody against programmed cell death-1 (PD-1). This phase II, single-arm study (ChiCTR1900023015) aims to evaluate the efficacy and safety of anlotinib plus sintilimab in patients with recurrent advanced cervical cancer. Methods: Patients who have received at least once platinum-based chemotherapy, histopathologically confirmed recurrent advanced cervical cancer (including squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma), more than 1% PD-L1 expression, ECOG 0-1 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and sintilimab was administered intravenously (200mg once every 3 weeks). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2019 and February 2021, 42 patients with a median age of 52 years (range:47-58), FIGO histopathological stage I (11.9%), II (31.0%), III (33.3%), IV (9.5%) and undiagnosed (14.3%) were enrolled. 39 of these patients were evaluable. In the efficacy-evaluable population (n = 39), the therapeutic evaluation showed that 2 and 20 patients achieved complete response and partial response respectively, yielding the ORR of 56.4% (22/39, 95% CI:40.2 to 71.5). The DCR was 94.9% (37/39, 95% CI:80.7 to 98.8). The median response time was 1.6 months. The median PFS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included hypothyroidism (33.3%), hypertension (23.8%), AST (21.4%), diarrhea (19.0%), ALT (16.7%), hand-foot syndrome(14.3%), hypertriglyceridemia (14.3%) and anemia (11.9%). The grade 3 AEs were hypertension (4.8%), hyponatremia (4.8%), immune pneumonia (2.4%) and immune myocarditis (2.4%). No higher AEs and treatment-related death were observed. Conclusions: Anlotinib plus sintilimab showed a promising efficacy with a favorable toxicity profile for patients with recurrent advanced cervical cancer. We will report more data in the future. Clinical trial information: ChiCTR1900023015.
Comparison of validated screening tools for the assessment of potentially inappropriate medications in older Indian patients with cancer.
Authors: Renita Castelino, Vanita Noronha, Anant Ramaswamy, Pallavi Rane, Shreya Gattani, Vandhita Nair, Kalpita Gawit, Ratan Dhekle, Manjunath Nookala, Vijay Maruti Patil, Shripad Dinanath Banavali, Kumar Prabash, Vikram Gota
Journal: Journal of Clinical Oncology (2021)

e24018 Background: The use of potentially inappropriate medication (PIM) and polypharmacy are highly prevalent in older cancer patients and are recognized as potential risk factors for adverse outcomes during cancer treatment. With geriatric cases increasing steadily in India, there is a need for comprehensive studies to identify a reliable screening tool for the assessment of PIMs. Methods: Retrospective analysis of patients ≥ 60 years who visited the Geriatric Oncology Clinic of the Tata Memorial Hospital, Mumbai, India between 2018-2021. Five tools (Beers-2015, STOPP and START-2014, PRISCUS-2010, FORTA-2018, and the EU (7)-PIM list-2015) were used to assess PIM. A standardized PIM value (SPV) was assigned for each patient for each scale which represented the ratio of the number of PIMs identified by a given scale to the total number of medications taken. The median SPV of all 5 scales for each patient was considered the reference standard. Agreement between each scale and the reference was carried out using Bland-Altman plots. The agreement was determined based on bias and the width of the limit of agreement. Association between categorical variables such as sex, comorbidities, and number of medications (above and below the median) and PIM use was determined using the chi-squared test. Results: 352 patients were included; median age - 70(range: 60-100) years, 287 (81.6%) were males. The bias and limit of agreement given by the Bland-Altman plot for each scale is shown in Table 1. The EU(7)-PIM list was found to have the least bias of 0.7% and the narrowest limits of agreement of 0.43 (-0.21 to 0.22). PIM use was observed to be significantly higher in patients with diabetes than without (83/281 versus 13/82, respectively, p = 0.013) and, patients prescribed with &gt; 7 medications compared with ≤7 (137/281 versus 06/70, respectively, p &lt; 0.001). Conclusions: The EU(7)-PIM list was found to have the least bias and thus considered the most reliable among all other scales in our study population. A high degree of discordance was observed between the tools, thus, we emphasize the need for future studies to identify the most reliable tool for the prediction of PIMs to aid clinical decision-making in geriatric practice.[Table: see text]
OPTIC primary analysis: A dose-optimization study of 3 starting doses of ponatinib (PON).
Authors: Jorge E. Cortes, Jane Apperley, Elza Lomaia, Beatriz Moiraghi, Maria Undurraga Sutton, Carolina Pavlovsky, Charles Chuah, Tomasz Sacha, Jeffrey Howard Lipton, Charles Schiffer, James K. McCloskey, Andreas Hochhaus, Philippe H. Rousselot, Gianantonio Rosti, Hugues De Lavallade, Michael J. Mauro, Tracey Hall, Vickie Lu, Shouryadeep Srivastava, Michael W Deininger
Journal: Journal of Clinical Oncology (2021)

7000 Background: PON, a third-generation tyrosine kinase inhibitor (TKI), demonstrated deep and long-lasting responses and survival in patients (pts) with chronic-phase chronic myeloid leukemia (CP-CML) resistant/intolerant to second-generation TKI therapy (PACE; NCT01207440); post hoc analysis suggested a relationship between dose and both adverse events and response. Here we present the primary analysis of OPTIC (NCT02467270), an ongoing, randomized, phase 2 trial with a novel response-based dosing regimen of PON in pts with resistant/intolerant CP-CML. Methods: Pts with CP-CML resistant/intolerant to ≥2 TKIs or with the BCR-ABL1 T315I mutation were randomized to PON starting doses of 45 mg (cohort A; 45 mg → 15 mg), 30 mg (B; 30 mg →15 mg), and 15 mg (C) once daily. Doses were reduced to 15 mg with achievement of ≤1% BCR-ABL1 IS in cohorts A and B. The primary endpoint is ≤1% BCR-ABL1 IS at 12 mo; secondary endpoints include cytogenetic and molecular responses and safety outcomes. AOEs were adjudicated prospectively by an independent review committee. Results: 283 pts were randomized (A/B/C: n=94/95/94) and had the following baseline characteristics: median age 48 y (18‒81 y); 98% received ≥2 (55% ≥3) TKIs; 99% had resistant disease; 40% had ≥1 baseline mutations (23% T315I). At the primary analysis with 32 mo median follow-up, 134 pts (47%; n=50/41/43) remained on treatment and 204 pts (72%) had PON exposure ≥12 mo. At 12 mo, 44% (41/93) in A, 29% (27/93) in B, and 23% (21/91) in C achieved ≤1% BCR-ABL1 IS (Table); primary endpoint was met by cohort A. Dose reductions to 15 mg after achieving response (A/B) were 48/29%. Most common grades ≥3 TEAEs were thrombocytopenia, 27%; neutropenia, 17%; and anemia, 7%. AOEs/serious AOEs were reported in cohorts A (10%/4%), B (5%/4%), and C (3%/3%). Dose reductions or discontinuations for TEAEs (A/B/C) were 46/35/32% and 19/16/14%, respectively. Conclusions: The OPTIC primary analysis demonstrates the optimal benefit:risk profile for PON was achieved with a response-based dosing regimen starting with 45 mg/d, followed by dose reduction to 15 mg/d upon achieving ≤ 1% BCR-ABL1 IS ; 30 mg→15 mg and 15 mg cohorts may provide benefit, especially in pts without T315I mutation (Table). The observed ≤1% BCR-ABL1 IS responses are supported by robust survival outcomes in pts with CP-CML resistant to second-generation BCR-ABL1 TKI therapy, both with and without BCR-ABL1 mutations. Clinical trial information: NCT02467270. [Table: see text]
Erratum: Establishing the identity of Anna Anderson Manahan (Nature Genetics (1994) 9 (9-10))
Authors: P. Gill, C. Kimpton, R. Aliston-Greiner, K. Sullivan, M. Stoneking, T. Melton, J. Nott, S. Barrit, R. Roby, M. Holland, V. Weedn
Journal: Nature Genetics (1995)
CONTACT-01: A phase III, randomized study of atezolizumab plus cabozantinib versus docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC) previously treated with PD-L1/PD-1 inhibitors and platinum-containing chemotherapy.
Authors: Joel W. Neal, Palak Kundu, Tomohiro Tanaka, Ida Enquist, Sid Patel, Alessia Balestrini, Jin Wang, Thomas Newsom-Davis, Yasushi Goto, Nick Pavlakis, Sang-We Kim
Journal: Journal of Clinical Oncology (2021)

TPS9134 Background: Patients with mNSCLC who progress on anti–PD-L1/PD-1 therapy administered in combination with or after platinum-based chemotherapy (PBC) are mainly treated with docetaxel or pemetrexed monotherapy. These therapies only have modest clinical activity, leaving a high unmet medical need. Cabozantinib, a tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment and may enhance the efficacy of PD-L1/PD-1 inhibitors, offering a promising second/third-line therapeutic opportunity for patients with mNSCLC. In a Phase Ib multi-cohort study (COSMIC-021; NCT03170960), cabozantinib plus atezolizumab (anti–PD-L1) showed an acceptable safety profile and promising efficacy (ORR: 27%; mDOR: 5.7 mo [range: 2.6-6.9]; disease control rate [CR + PR + SD]: 83%) in 30 patients with mNSCLC who had progressed after prior anti–PD-L1/PD-1 therapy plus chemotherapy (Neal et al. J Clin Oncol 2020). The Phase III CONTACT-01 study will further evaluate the efficacy and safety of atezolizumab plus cabozantinib versus docetaxel monotherapy in patients with mNSCLC who have progressed during or after prior treatment with anti–PD-L1/PD-1 therapy and PBC. Methods: CONTACT-01 (NCT04471428) is a Phase III, multi-center, randomized, open-label study that will enroll ≈350 patients from 150 to 200 sites internationally. Key eligibility criteria include histologically or cytologically confirmed mNSCLC, disease progression with concurrent or sequential anti–PD-L1/PD-1 treatment and PBC, measurable disease (RECIST 1.1), ECOG PS of 0-1 and the availability of tissue specimens for centralized PD-L1 testing or known PD-L1 status using a health authority–approved PD-L1 assay. Patients with NSCLC previously treated with cabozantinib, docetaxel or anti–PD-L1/PD-1 + VEGFR TKIs are excluded. Patients with known sensitizing EGFR/ALK mutations and active or untreated CNS metastases are also excluded. Patients will be randomized 1:1 to receive either atezolizumab (1200 mg IV every 3 weeks) + cabozantinib (40 mg orally once daily) or docetaxel (75 mg/m 2 IV every 3 weeks). The primary endpoint is OS. Secondary endpoints include investigator-assessed PFS, ORR and DOR per RECIST 1.1; TTD in patient-reported physical function and global health status (EORTC QLQ-C30); investigator-assessed PFS rates at 6 months and 1 year; OS rates at 1 and 2 years; safety and PK. Clinical trial information: NCT04471428.
Differences in disease characteristics and outcomes in older versus younger adults with multiple myeloma.
Authors: Michael Jacobs, Spencer Langerman, Andrzej J. Jakubowiak, Brian C Chiu, Benjamin Avi Derman
Journal: Journal of Clinical Oncology (2021)

e20041 Background: Older adults are underrepresented in clinical trials in multiple myeloma (MM), as are the risk prognostication schema derived from them, which limits their generalizability to this age group. Despite appropriate fitness, older adults may not be offered the same therapies as their younger counterparts. In this study, we compared disease characteristics and their associations with outcomes in older and younger adults with MM. Methods: We obtained data for newly diagnosed MM patients from the MM Research Foundation CoMMpass registry (version IA16), a prospective observational study with highly annotated clinical data, cytogenetics, and longitudinal outcomes. Chi-square or Fisher’s exact test were used for comparisons of categorical variables. Progression free survival (PFS) and overall survival (OS) curves were constructed using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazard models were computed to estimate hazard ratio (HR) and 95% confidence interval (CI) for association between pre-treatment variables and outcomes. Results: 1,143 patients were analyzed, including 853 patients (pts) under age 70 years (&lt; SEV) and 290 pts age 70+ years (SEV+). SEV+ had a higher frequency of ISS score 3 (p &lt; 0.001), lower estimated glomerular filtration rate (median 57.6 vs 74.7 mL/min/1.73m 2 , p &lt; 0.001), and worse ECOG performance status (PS) (p = 0.01). Of the cytogenetic abnormalities analyzed [del17p, gain1q, t(4;14), t(8;14), t(14;16), t(14;20), and hyperdiploidy], SEV+ had higher frequency of gain1q (42% vs 33%, p = 0.02) and t(14;20) (3% vs 1%, p = 0.03) compared with younger adults. SEV+ received less proteasome inhibitor + immunomodulatory imide triplet induction therapy (27% vs 55%, p &lt; 0.001) and less frontline autologous stem cell transplant (ASCT) (22% vs 59%, p &lt; 0.001). SEV+ were less likely to achieve &gt;complete response to induction therapy compared to &lt; SEV (32% vs 18%, p &lt; 0.001). SEV+ had worse PFS (HR 1.8, 1.6-2.2, p &lt; 0.001) and OS (2.3, 1.8-2.9, p &lt; 0.001) compared to &lt; SEV. On multivariate analysis, increasing ISS, gain1q, high risk gene expression profiling (UAMS70), and lack of triplet induction with frontline ASCT were associated with both poorer PFS and OS in &lt; SEV. For SEV+, multivariate analysis revealed that increasing ISS, t(14;16), and lack of triplet+ASCT were associated with inferior PFS, while age, male sex and increasing ISS were associated with inferior OS. Conclusions: Older adults have a greater prevalence of ISS 3, gain1q, and t(14;20) compared with younger adults but only ISS translates into inferior PFS or OS within this group. Increased access to triplet induction therapy and expanding access to frontline ASCT among older adults may help to improve outcomes in this growing subset of patients.
Prognostic Value of Vasodilator Stress Perfusion Cardiovascular Magnetic Resonance in Patients With Prior Myocardial Infarction
Authors: Théo Pezel, Philippe Garot, Marine Kinnel, Thierry Unterseeh, Thomas Hovasse, Stéphane Champagne, Valentin Landon, Solenn Toupin, Francesca Sanguineti, Jérôme Garot
Journal: JACC. Cardiovascular imaging (2021)
Daily step counts to predict hospitalizations during chemoradiotherapy for head and neck cancer.
Authors: Elena S. Izmailova, Andrew Cohen, Rafi Kabarriti, Jeremy Eichler, Chengrui Huang, Nitin Ohri
Journal: Journal of Clinical Oncology (2021)

1571 Background: Wearable activity trackers could provide useful data for managing cancer patients with respect to treatment selection, toxicity monitoring, and implementation of supportive care measures. Here, we seek to evaluate the association between daily step counts and hospitalizations in a cohort of patients with head and neck cancer (HNC). Methods: This analysis consists of patients enrolled in one of three prospective trials involving activity monitoring (NCT02649569, NCT03115398, NCT03102229) during chemoradiation. Study subjects were asked to wear a commercial fitness tracker continuously during the therapy. ECOG performance status (PS) was assessed at baseline, and quality of life (QoL) EORTC QLQ-C30 questionnaires were completed weekly. Multivariable Cox regression models with time-dependent covariates (average step count over the past 3 days, most recent QoL score) and time-fixed covariates (age, sex, baseline PS, study number, baseline tumor volume, and treatment setting [definitive versus postoperative]) were used to identify predictors of first hospital admission during the chemoradiotherapy course. In addition to the Cox regression models, linear mixed models were fitted with daily step count as the dependent variable to examine its relationship with certain independent variables including age, sex, weekend status, days after treatment initiation, and study number. Results: Sixty-six HNC patients who received chemoradiotherapy between 2015 and 2019 were included in the analysis. Median age was 60 (range: 27-88). 47% of patients had ECOG PS score 0, 47% ECOG score 1, and 6% ECOG score 2. 29% of patients had HPV-positive oropharyngeal tumors, and the most common other tumor subsites were larynx (27%), and nasopharynx (12%). The Cox regression survival model demonstrated a 26% reduction in the short-term hospitalization risk for every 1000 daily steps (averaged over the past 3 days, hazard ratio 0.74; 95% confidence interval (CI) 0.55-0.98, p = 0.0367). Hospitalizations were not significantly associated with most recent QoL or baseline ECOG PS. Additionally, according to the linear mixed model results, daily step count was not associated with age (p = 0.8048). Study subjects moved less on weekends (on average 245 fewer steps on weekends than weekdays, 95% CI 134-357, p &lt; 0.0001). Also, an increase in most recently measured ECOG PS was associated with a decrease in daily step count (167 fewer steps for every increase in ECOG PS, 95% CI -289 to -45, p &lt; 0.0072). Conclusions: Daily step counts are a dynamic predictor of hospitalizations in patients undergoing chemoradiotherapy for head and neck cancer. Interventional studies are needed to demonstrate feasibility of leveraging physical activity data to optimize supportive care during cancer therapy and enhance cancer care quality. Clinical trial information: NCT02649569, NCT03115398, NCT03102229.
Left Ventricular Ejection Fraction Assessment in Patients with Congestive Heart Failure
Authors: Jane M Larson, Carolyn V Harper, Rita Redberg
Journal: Circulation (2001)

P48 Background: The US Agency for Health Care Policy and Research guidelines state that any patient with suspected heart failure should have ejection fraction assessment performed. This study describes factors associated with left ventricular ejection fraction (LVEF) assessment in patients with congestive heart failure (CHF). Methods: A random sample of 1608 patients aged 65 and older were selected from all fee-for-service Medicare beneficiaries discharged from California hospitals in 1998 with a principal diagnosis of CHF. Patients were excluded if a diagnosis of CHF was not confirmed, if the patient died, was transferred to another acute care facility, left against medical advice, or had a procedure code for dialysis. The outcome measure was LVEF assessment. Results: After exclusions, 1562 patients remained of whom 1000 (64%) had LVEF either assessed during this hospitalization, prior to this hospitalization, or had a documented plan for LVEF evaluation after discharge. In multivariate analysis, controlling for age, gender, race, and past history of CHF, patients who did not have a LVEF assessment were less likely to have been prescribed an angiotensin converting enzyme (ACE) inhibitor (Odds Ratio=0.25, 95% Confidence Interval=0.20-0.31). Patients age 85 years and older were less likely to have LVEF assessed (OR=1.52, 95% CI=1.13-2.05). Conclusion: CHF patients who do not have a LVEF assessment are much less likely to receive an ACE inhibitor. Over one third of CHF patients do not undergo LVEF assessment, contributing to under-prescription of ACE inhibitors in CHF. Efforts to improve quality of care for CHF patients may need to promote LVEF assessment as a first step in CHF management.
Survival outcomes in patients receiving immune checkpoint inhibitor (ICI) for metastatic small cell urothelial cancer (SCUC).
Authors: Omar Alhalabi, Nathaniel Wilson, Neema Navai, Matthew T Campbell, Amishi Yogesh Shah, Jianjun Gao, Paul G. Corn, Ana Aparicio, Bogdan Czerniak, Charles Guo, Christopher Logothetis, Nizar M. Tannir, Seungtaek Choi, Arlene O. Siefker-Radtke
Journal: Journal of Clinical Oncology (2021)

4543 Background: The prognosis in patients with metastatic SCUC (mSCUC) remains poor with median survival around 1 year with systemic chemotherapy. We aimed to investigate the impact of ICI on survival of patients with mSCUC. Methods: Patients who received systemic therapy at MD Anderson Cancer Center (MDACC) for de novo or metachronous mSCUC after completing local management. within 12 months of neoadjuvant or adjuvant chemotherapy were included in this cohort, with overall survival (OS) calculated from the time of receipt of initial chemotherapy. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using logrank test. Results: 102 patients with mSCUC received systemic therapy at MDACC between April 2006 and June 2020. Median age was 66 (range 24 – 86 years), male to female ratio was 5. Bladder was the primary site in 85 (83%), 45 (44%) had prior cystectomy and 9 (9%) had prior nephroureterectomy. Histologies included 51 (50%) with predominant small cell (SC) features, 28 (27%) with focal SC features, 20 (20%) with pure SC, and 3 (3%) mixed with large cell component. Thirty-nine (38%) received ICI during their disease course: 29 (28%) following front-line chemotherapy (15 of whom within 12 months of neoadjuvant/adjuvant platinum therapy), 5 (5%) combined with front-line chemotherapy, and 5 (5%) received ICI front-line (two of whom were able to receive second-line chemotherapy). ICI agents used included anti-PD-1 (n=19), anti-PD-L1 (n=12), anti-PD-1/anti-CTLA-4 (n=5), anti-PD-1/anti-TIM3 (n=1), anti-PD-1/anti-STAT3 (n=1), anti-PD-L1/PARPi (n=1). Those who received ICI at any time had an improved median OS compared to those treated with chemotherapy alone (20.1 vs 12 months), [HR=0.45, 95% CI 0.27-0.72, p=0.003]. When we limited the analysis to those with de novo mSCUC (n=36), those who received ICI at any time (n=13) had an improved median OS compared to those treated with chemotherapy alone (n=23) (not reached vs 9.41 months), [HR=0.28, 95% CI 0.12-0.68, p=0.03]. Among patients who received ICI (n=39), median OS in those with liver metastases (n=11) was numerically shorter than those without (n=28) (13.1 vs 21.6 months), [HR=1.83, 0.59-5.7, p=0.21]. Conclusions: ICI improves OS for patients with mSCUC. Although clinical trials remain difficult in these rare variants, further prospective studies are indicated to confirm this finding.