tbuckley/cabot-search huggingface dataset:
Two dosing regimens of nivolumab (NIVO) plus ipilimumab (IPI) for advanced (adv) melanoma: Three-year results of CheckMate 511.
Authors: Celeste Lebbe, Nicolas Meyer, Laurent Mortier, Ivan Marquez-Rodas, Caroline Robert, Piotr Rutkowski, Marcus O. Butler, Thomas Eigentler, Alexander M. Menzies, Michael Smylie, Ana Maria Arance, Paolo Antonio Ascierto, Inge Marie Svane, Mazhar Ajaz, Nikhil I. Khushalani, Maurice Lobo, Jesus Zoco, Jacopo Pigozzo
Journal: Journal of Clinical Oncology (2021)

9516 Background: NIVO 1 mg/kg plus IPI 3 mg/kg (NIVO1 + IPI3) is approved for treatment (tx) of unresectable/adv melanoma, with demonstrated durable clinical benefit on long-term follow-up. Analysis of the phase 3b/4 CheckMate 511 study (NCT02714218) at 1 y showed that NIVO 3 mg/kg plus IPI 1 mg/kg (NIVO3 + IPI1) improves the safety profile of the combination; efficacy with the 2 regimens was similar in descriptive analyses. Here we present 3-y safety/efficacy results. Methods: Patients (pts) ≥ 18 y of age with previously untreated unresectable stage III/IV melanoma were randomized 1:1 to receive NIVO3 + IPI1 Q3W × 4 (N = 180) or NIVO1 + IPI3 Q3W × 4 (N = 178), both followed by NIVO 480 mg Q4W until progression/unacceptable toxicity. The primary endpoint was the incidence of grade (gr) 3–5 tx-related adverse events (TRAEs); secondary endpoints (descriptive analyses) included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The study was not powered to formally demonstrate noninferiority for efficacy endpoints. Results: At a median follow-up of 44.4 and 43.9 mo in the NIVO3 + IPI1 and NIVO1 + IPI3 groups, respectively, TRAEs led to tx discontinuation in 26% and 39% of pts; 57% and 42% of pts had received maintenance therapy. Gr 3–5 TRAE incidence remained significantly lower with NIVO3 + IPI1 than NIVO1 + IPI3 (33.9% vs 48.3%; odds ratio 0.55 [95% CI 0.36–0.84]). The most frequent TRAEs (any gr) were diarrhea (27%), fatigue (26%), and pruritus (26%) with NIVO3 + IPI1 and diarrhea (31%), pruritus (29%), and rash (27%) with NIVO1 + IPI3. In descriptive analyses, efficacy results were similar to those observed at 1 y. OS and tx-free–analysis outcomes were numerically similar in the 2 groups (table). Conclusions: At 3-y follow-up, NIVO3 + IPI1 continued to demonstrate an improved safety profile compared with NIVO1 + IPI3. In descriptive analyses, both groups demonstrated high 3-y OS rates that were numerically similar. This study provides important information regarding the benefit–risk profile of both dosing regimens of NIVO + IPI in pts with adv melanoma. Clinical trial information: NCT02714218. [Table: see text]
Predictors of 30-day readmission rate after liver transplant in patients with hepatocellular carcinoma.
Authors: Miguel Salazar, Shristi Upadhyay Upadhyay Banskota, Lou Anne Acevedo, Pedro Palacios, Estefania Gauto, Binav Baral, Trilok Shrivastava, Nabin Khanal
Journal: Journal of Clinical Oncology (2021)

e16193 Background: Liver transplantation (LT) is curative for hepatocellular carcinoma (HCC) in patients within the Milan criteria. Readmissions are common postoperatively, and can be associated with increased morbidity and healthcare burden. Hence we aim to identify incidence, impact and independent predictors for readmission in patients who underwent LT in HCC. Methods: Retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for LT with an underlying diagnosis of HCC, in patients with cirrhosis we used the BAVENO score to categorize between compensated and decompensated cirrhosis. We aim to identify 30-day readmission rate, mortality, healthcare related utilization resources and independent predictors of readmission. Results: A total of 2,092 patients with HCC underwent liver transplantation. The 30-day readmission rate was 25.6%. Main causes for readmission were post-surgical complications from LT, sepsis, liver failure. Readmitted patients were less likely to have private insurance (40.5% vs 34.5%; P&lt;0.01), to be obese (18.2% vs 7.9%; P&lt;0.01), hypertensive (51.2% vs 39.5%; P&lt;0.01), have history of non-alcoholic steatohepatitis (16.5% vs 2.3%; P&lt;0.01). Readmission was associated with higher in-hospital mortality rate (0.1% vs. 1.5%; P&lt;0.01). The total health care in-hospital economic burden of readmission was $56.1 million in total charges and $15.2 million in total costs. Independent predictors of readmission were type 2 diabetes, transfusion of blood products during index admission, protein-caloric malnutrition, sepsis, and preventive factors were younger age, private insurance and cannabis use. Conclusions: Readmissions after LT in HCC are associated with higher mortality and pose a high health care burden. We identified risk factors that can be targeted to decrease overall patient morbidity, mortality and health care burden.[Table: see text]
Clinicogenomic real-world data analysis of patients (pts) with <i>KRAS G12C-</i>mutant advanced non-small cell lung cancer (aNSCLC) from the natural history cohort of the Blood First Assay Screening Trial (BFAST).
Authors: Rafal Dziadziuszko, Xiao Li, Eric C. Anderson, Alona Zer, Luis Corrales-Rodriguez, Parneet Cheema, Aleksandra Szczesna, Manuel Philco, Michael Mathisen, Sarah M. Paul, Vijay Bhagawati-Prasad, Gaurav Pathria, Zhen Shi, Magalie Hilton, qing zhang
Journal: Journal of Clinical Oncology (2021)

9023 Background: BFAST (NCT03178552) is a global, multicohort trial of targeted therapies or cancer immunotherapy (CIT) in treatment (tx)-naive aNSCLC. Pts are screened for the study using comprehensive blood-based next-generation sequencing (NGS). In the BFAST natural history cohort, data were collected for pts who received tx or care outside the study’s interventional cohorts. Here, we analyzed the subset of pts whose tumors have KRAS G12C mutations (mut). Methods: Pts eligible for blood-based NGS screening had unresectable aNSCLC, ECOG PS 0-2 and no prior systemic tx for aNSCLC. Pts without tissue samples were eligible. Key genomic and molecular features, including bTMB, PD-L1 and ctDNA concentration; cancer tx; tx response and survival data were collected and analyzed in an exploratory analysis. Results: In the full BFAST screening population through December 2020 (N = 5917), 23% of pts had tumors with any KRAS mut; 9% were KRAS G12C. Pts were enrolled in the natural history cohort from October 2018 to October 2020 (n = 1017); 63 pts had tumors with KRAS G12C mut. Median age was 68 y, 59% were male, 86% had ECOG PS 0-1 and 84% had non-squamous histology. Co-mut in TP53 (60%) and STK11 and/or KEAP1 (25%) were detected; 8% of pts had bTMB ≥16. High PD-L1 expression per local testing was reported in 32% of pts; 38% were not tested. Among pts with 1L tx (n = 50), 50%, 28% and 20% received chemo, CIT or CIT + chemo, respectively, with real-world response rates (CR/PR per physician assessment) of 20%, 29% and 30%, respectively. Of the 13 pts (21%) without documented 1L tx, 7 died ≤3 mo from enrollment. Median OS was 14 mo overall, with differences found between key genomic subsets (Table). Conclusions: BFAST is the first study to identify KRAS G12C mut using blood-based NGS and describe the natural history, clinical characteristics and genomic landscape of this pt subset. Up to 21% of pts may not receive 1L tx. Pts with TP53 co-mut appear to have favorable outcomes, while those with STK11 and/or KEAP1 co-mut appear to have inferior outcomes vs pts without these mut. The lack of PD-L1 testing in many pts indicates a lack of tissue for comprehensive tissue testing, highlighting a potential benefit of blood-based detection of biomarkers, including KRAS G12C. Clinical trial information: NCT03178552. [Table: see text]
Adaptive lymphocyte profile analysis discriminates mild and severe forms of COVID-19 after solid organ transplantation
Authors: Arnaud Del Bello, Nassim Kamar, Francois Vergez, Stanislas Faguer, Olivier Marion, Audrey Beq, Yasmine Lathrache, Florence Abravanel, Jacques Izopet, Emmanuel Treiner
Journal: Kidney International (2021)
Implications of mRNA-based SARS-CoV-2 vaccination for cancer patients
Authors: Emanuela Romano, Steve Pascolo, Patrick Ott
Journal: Journal for ImmunoTherapy of Cancer (2021)

SARS-CoV-2 infection and the resulting COVID-19 have afflicted millions of people in an ongoing worldwide pandemic. Safe and effective vaccination is needed urgently to protect not only the general population but also vulnerable subjects such as patients with cancer. Currently approved mRNA-based SARS-CoV-2 vaccines seem suitable for patients with cancer based on their mode of action, efficacy, and favorable safety profile reported in the general population. Here, we provide an overview of mRNA-based vaccines including their safety and efficacy. Extrapolating from insights gained from a different preventable viral infection, we review existing data on immunity against influenza A and B vaccines in patients with cancer. Finally, we discuss COVID-19 vaccination in light of the challenges specific to patients with cancer, such as factors that may hinder protective SARS-CoV-2 immune responses in the context of compromised immunity and the use of immune-suppressive or immune-modulating drugs.
Immune cell counts and perceived cognitive impairment before and after chemotherapy among 544 women with breast cancer.
Authors: Elizabeth Belcher, Nikesha Gilmore, Lee Kehoe, Ian Kleckner, Amber Kleckner, Abdi Gudina, Sara Hardy, Huiwen Xu, Judith O. Hopkins, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2021)

12114 Background: In a nationwide prospective study, we found that patients with breast cancer had greater perceived cognitive impairment (PCI) before and after chemotherapy compared to controls without cancer. To gain further insight into the role that inflammation plays in cognitive function, we evaluated relationships between immune cell counts and lymphocyte:monocyte ratio with PCI at pre- and post- chemotherapy. Methods: Data were collected as part of longitudinal cohort study conducted through the National Cancer Institute Community Oncology Research Program network (NCT01382082). Self-reported PCI was scored at pre-chemotherapy (0-7 days before first chemotherapy) and post-chemotherapy (0-30 days after last chemotherapy) from the PCI sub-scale of the Functional Assessment of Cancer Therapy: Cognitive Function (possible score range 0-72). Immune cell counts were measured by complete blood count with differential at pre- and post- chemotherapy. Lymphocyte:monocyte ratio (LMR) was calculated. Separate linear regression models evaluated the association of immune cell counts and LMR with 1) pre-chemotherapy PCI and 2) post-chemotherapy PCI. Models were adjusted for age, cognitive reserve (reading score), anxiety, and depression. Results: PCI and immune cell data were available for 544 patients at pre-chemotherapy and 532 at post-chemotherapy. Subjects had a mean age of 53.1 (SD=10.8). At pre-chemotherapy, higher basophil count and higher LMR were significantly associated with worse PCI (β=5.73, SE=2.37, p&lt;0.05; β=0.047, SE=0.02, p&lt;0.05, respectively). Higher basophil count and higher LMR were also significantly associated with worse PCI at post-chemotherapy (β=5.84, SE=2.92, p&lt;0.05; β=1.01, SE=0.48, p&lt;0.05). Conclusions: These data support the hypothesis that inflammation is associated with perceived cognitive function before and after chemotherapy in adults with breast cancer. Targeting inflammatory processes may be beneficial for reducing cancer-related cognitive impairment. Funding: NCI UG1CA289961, T32CA102618, R01CA231014, DP2CA195765.
Outcome of neoadjuvant treatment in triple-negative breast cancer in a rural underserved community.
Authors: Martin Majer, Elizabeth Fauchier Little, Sarah Jones, Jasmine Dong, David Hutton, Karolina Bezdickova, Lucie Tomanova, John Promlap, Tien Promlap, Greg Schneringer, Steve DeMartini, Michael Russell, April Joyner, Susan Schmidt, Ravi Nagubandi, Randell Skau, Monica Swars, Megan Powell, Edward J. Ordorica
Journal: Journal of Clinical Oncology (2021)

e12608 Background: Complete pathological response (pCR) is a surrogate of successful neoadjuvant treatment of triple-negative breast cancer (TNBC). We extended our study from 2016, where we discussed unusually high pCR employing taxane/platinum (T/P) without the use of adriamycin and cyclophosphamide (AC). Methods: This is a retrospective observational study of an underserved, low income, rural population in Oroville, California over 10 years (2011-2021). Neoadjuvant chemotherapy was offered to eighteen women with ages ranging from 36 to 77 years old (mean age is 56). Minimum requirements for evaluation was three cycles administered within 90 days of starting treatment. The primary end point of this study was pCR. We analyzed the relationship between pCR, chemotherapy regimen, proliferation rate of original tumor by Ki-67 and the ratio of neutrophil and lymphocyte (NLR). The two regimens of chemotherapy included both standard AC+T or the alternative treatment with T/P. We grouped Ki-67 to above and below 50% pre-treatment. NLR was grouped between those above and below 3.2. Results: Our study produced a respectable response rate with 12/18 (67%) achieving pCR. There was no difference with or without exposure to anthracyclines. Out of the twelve who achieved pCR, eight (67%) received T/P and four (33%) got AC+T. Ki-67 in all eighteen patients ranged from 2% to 97% with a median of 75%. Ki-67 was &gt;50% in 10/12 (83%) patients who achieved pCR and 3/6 (50%) in those who did not have a response. NLR was a significant predictor for pCR. 8/12 (67%) of patients who experienced pCR had a NLR of &lt;3.2 compared to the 1/6 ( 17%) with no response. The p-value is .0455. Conclusions: Treatment with the alternative regimen of T/P didn’t affect pCR in our population. We hypothesize that some of the beneficial effects of cytotoxics affected the patient’s immunological milieu on top of the direct effect of the malignant clone.
Abstract 16: A Minipig Genetic Model of Hypertrophic Cardiomyopathy
Authors: Eric M Green, Robert M Weiss, Abhay Divekar, Sadie R Bartholomew Ingle, Marcus Henze, Raja Kawas, Lindsey Gifford, Melissa K Davis, Frank Rohret, Daniel R Thedens, Hector M Rodriguez, Marc J Evanchik, Robert L Anderson, Jessica Sieren, Christopher S Rogers, David K Meyerholz, Ferhaan Ahmad
Journal: Circulation Research (2017)

Introduction: Hypertrophic cardiomyopathy (HCM) is a heritable disease of heart muscle associated with increased risk of heart failure and sudden death. Mutations in genes encoding sarcomere protei...
Impact of RxPONDER on breast cancer treatment in an academic-community hospital.
Authors: Be Saito, Cathryn Johnson, Lina Sizer, Catherine Carruthers, Elena Lamb, W. Bradford Carter, Thomas G. Frazier
Journal: Journal of Clinical Oncology (2021)

e12524 Background: The introduction of Oncotype Dx set the stage for targeting chemotherapy treatment to only patients who would derive a benefit. RxPONDER trial then demonstrated that postmenopausal women with 1-3 positive lymph nodes, could forego chemotherapy if the recurrence score (RS) was ≤25. The most common chemotherapy regimens for breast cancer are taxotere and cytoxan or dose dense adriamycin/cytoxan followed by taxol. Chemotherapy can have many side effects and can increase risk of hospitalization due to complications. In addition, the financial cost can be considerable. Four cycles of TC will approximately cost $59,000, and most patients likely receive doses of growth factor support (neulasta is $12,565 per dose), totaling at minimum to $100,000 per patient. The purpose of this study was to look at the impact of RxPONDER on our patients. We reviewed patients who had RS at our institution in the last 5 years to see if we were appropriately treating patients with chemotherapy and hormonal therapy, or if a large group could be treated with hormonal therapy alone. Methods: This was an IRB approved retrospective chart review of patients at an academic-community hospital from 2015-2019. We identified patients ≥50 years old diagnosed with ER+/HER2- node positive breast cancer. Exclusion criteria included: M1, pN2, pN3. Univariate analysis used to compare patients that had RS vs those that did not. Student’s t-test was used to analyze whether there was a difference in rate of patients getting chemotherapy based on RS. Results: 216 patients were identified with ER+/Her2- breast cancer and 1-3 positive lymph nodes. 142 had RS (65.7%). Of those with RS, 140 were T1-T2 (98.6%), 131 had 1-2 positive LNs (92.3%), 115 had RS≤25 (80.9%), and 56 received chemotherapy (39.4%). Of the 74 patients without RS, 60 were T1-T2 (94.6%), 69 had 1-2 positive LNs (93.2%), and 51 received chemotherapy (68.9%). 30 patients who met the RxPONDER criteria (postmenopausal, 1-3 positive lymph nodes, and RS ≤25) still received chemotherapy. Conclusions: If we apply the RxPONDER trial recommendations, 30 patients would have been spared chemotherapy. In addition, 54.2% RxPONDER patients had RS ≤25. Extrapolated by percentage, 40 of the 74 patients who did not get RS in our study may have also been spared the side effects and cost of chemotherapy. This would be a savings of at least $3-7 million dollars to the health care system. RxPONDER makes a significant impact, not only in appropriately deescalating breast cancer treatment, but also to counter the increasing cost of medical care.[Table: see text]
Validation of National Comprehensive Cancer Network Guidelines (NCCN) at a single institution.
Authors: Daniel Powell Dolan, Emily Polhemus, Daniel N. Lee, Chris Gentilella, Hisashi Tsukada, Raphael Bueno, Hassan Khalil, Abby White, Scott James Swanson
Journal: Journal of Clinical Oncology (2021)

e20556 Background: Invasive mediastinal staging is necessary to identify locally advanced non-small cell lung cancer (NSCLC). We sought to validate NCCN guidelines for invasive mediastinal staging. Methods: We retrospectively reviewed all patients who had curative lung resection for pathologically confirmed NSCLC from October 2018 to December 2019. We excluded patients who had induction therapy without undergoing invasive mediastinal staging first. We evaluated methods of mediastinal staging, staging results, and final pathology. Indications for staging were one or more of the following; mediastinal lymph nodes &gt; 1.0cm in short axis, Standardized Uptake Value of &gt; 3.0 on Positron Emission Tomography, &gt; 50% of tumor on medial side of mid-clavicular line (central vs peripheral), or peripheral lesion &gt; 3.0cm in diameter. Staging methods were mediastinoscopy, endobronchial ultrasound (EBUS), and video-assisted thoracoscopic surgery (VATS) ipsilateral mediastinal staging before resection of main tumor. Results: In total, 457 lung resections were performed. Staging was done in 144/275 indicated cases (52.4%). Mediastinoscopy was completed in 49 patients, with 20.4% (n = 10) N2-positive. The false negative rate of mediastinoscopy was 4.1% (n = 2 at station 7). EBUS was performed in 64 patients and 21.9% (n = 14) were N2 positive. The false negative rate for EBUS was 3.1% (n = 2 at station 7). Two mediastinoscopy and 9 EBUS patients had 0 N2 stations sampled. None of the patients were ultimately N2 positive. Staging of three mediastinal stations (4L, 4R, and 7) was done in 26/49 mediastinoscopies and 15/64 EBUS. Of 20 patients who had VATS ipsilateral mediastinal staging, none were N2 positive and there were 0 false negatives. This left 131 patients who did not received indicated staging. The most common indication in this group was central location, 83.2% (n = 109). Four of these unstaged patients were N2 positive at resection (3.1%). The sole indication for these 4 patients was a centrally located tumor. Clinical tumor sizes were 1.2 cm, 1.3 cm, 1.5 cm, and 1.9 cm. Overall, the N2-positive rate of the staged group was 24/144 (16.7%) vs 4/131 (3.1%) N2 positive in the unstaged group, p &lt; 0.001. Conclusions: The current NCCN staging guidelines accurately reflect the risk of N2 disease for NSCLC. The indication of central location for tumors may benefit from being reevaluated in a larger cohort, particularly given efficacy of adjuvant therapy.
Head-to-head comparison of single agent (SA) plinabulin (Plin) versus pegfilgrastim (Peg) for the prevention of chemotherapy-induced neutropenia (CIN) in the phase 3 trial PROTECTIVE-1.
Authors: Douglas W. Blayney, Yuankai Shi, Igor Bondarenko, Stephan Ogenstad, Qingyuan Zhang, Lihua Du, Lan Huang, Ramon Mohanlal
Journal: Journal of Clinical Oncology (2021)

547 Background: Peg is the current standard of care (SoC) for the prevention of CIN, with a low absolute neutrophil (N) count (ANC) week 1 after chemotherapy (chemo) with normalization in week 2. Breakthrough designation agent from FDA, Plin, a novel, non-G-CSF agent for the prevention of CIN, produces a normal ANC in week 1 of cycle (C) 1 by potentially protecting progenitor cells in bone marrow from chemo assault, and also has anticancer activity (Blayney, St Gallen 2019; ASCO 2019). Here we report data from a pre-specified interim analysis from PROTECTIVE-1 (Study 105; NCT03102606). Methods: Breast cancer (BC), lung (NSCLC) and prostate cancer (HRPC) pts with at least 1 risk factor as per NCCN, received docetaxel (Doc) 75 mg/m2 with either Peg 6mg (n=53) or Plin 40 mg (n=52) over 4 cycles, and had ANC blood draws on Day (D) 1, 2,6,7,8,9,10,15 in C1 (Covance Central Laboratory). Plin was given on D1, as a 30 min IV infusion, 30 min after Doc, and Peg, 24 hrs after Doc. Primary objective was to demonstrate non-inferiority (NI) of SA Plin vs SA Peg for duration of severe neutropenia (DSN) in C1. NI of Plin vs Peg would be declared if the upper limit of 95% confidence interval for the mean DSN difference between Plin and Peg would be &lt;0.65 day. Other endpoints included C1 platelet count, C1 bone pain scores (validated questionnaire), C1-4 clinical sequelae of CIN through [febrile neutropenia (FN), infection, antibiotic and hospitalization rate, and Doc discontinuation (Discont) and delays], and safety (AEs, hematology and chemistry, vital signs) Results: Predefined DSN NI criterion between SA Plin and SA Peg was met. C1 Grade 4 toxicity was not different between Plin and Peg (p=NS). Clinical sequelae of CIN were comparable or slightly better for Plin vs Peg (see Table). Plin caused less bone pain (p=0.01) and less thrombocytopenia (p&lt;0.0001 on D15) vs Peg. AE frequency and overall safety was comparable for SA Plin and SA Peg. Conclusions: SA Plin has efficacy for Doc CIN prevention non-inferior compared to SoC Peg, and accordingly has comparable (or numerically better) profile for clinical sequelae of CIN. Plin has an advantage for bone pain, platelet counts, convenience of use (same day vs next day dosing) over SoC Peg and has anticancer activity. Clinical trial information: NCT03102606. [Table: see text]