tbuckley/cabot-search huggingface dataset:
Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma
Authors: Francesco Tovoli, Vincenzo Dadduzio, Stefania De Lorenzo, Lorenza Rimassa, Gianluca Masi, Massimo Iavarone, Fabio Marra, Ingrid Garajova, Maria Pia Brizzi, Bruno Daniele, Franco Trevisani, Carlo Messina, Francesco Di Clemente, Sara Pini, Giuseppe Cabibbo, Alessandro Granito, Mario Domenico Rizzato, Vittorina Zagonel, Giovanni Brandi, Tiziana Pressiani, Piera Federico, Caterina Vivaldi, Irene Bergna, Claudia Campani, Fabio Piscaglia
Journal: Liver Cancer (2021)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) &amp;#x3e; 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) &amp;#x3e;400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4–14.8) and 5.1 (3.3–6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3–4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS &amp;#x3e; 0, and AFP &amp;#x3e;400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials.
Covid-19 infection in patients with a history of everolimus use.
Authors: Metin Pehlivan, Adnan Aydiner
Journal: Journal of Clinical Oncology (2021)

e18744 Background: The COVID-19 infection, declared as a pandemic by WHO in March 2020, continues its effects all over the world. Cancer patients also get COVID infection and in some patients this infection is mortal. In our study, we examined the course of COVID-19 infection in patients who actively or in the past used Everolimus. Methods: Patients who used everolimus actively or in the past were examined in our study. Patients who survive after the first cases seen in Turkey March 11, 2020 ; were evaluated in terms of whether they had COVID-19. Demographic characteristics and primary malignancies of the patients were examined. Patients who had COVID-19 infection and died were identified. Results: Our study consists of 50 patients in total. 14 (28%) of the patients were male and 36 (72%) were female. The average age of the patients is 56.72 (28-82), the average age of the male patients is 52.8 (28-80) and the average age of the female patients is 57.58 (36-82). 17 of the patients were treated for breast cancer, 11 for neuroendocrine tumor, 7 for tuberous sclerosis, 5 for renal cell carcinoma, 4 for thymic carcinoma, 2 for thymoma, 2 for ovarian ca, 2 for perivascular ecrine tumor. While it is the most common breast cancer in women (47.2% of female patients), neuroendocrine tumor is the most common in male patients (35.7% of male patients). While 13 patients were actively using everolimus (26%), 37 patients (74%) had discontinued everolimus treatment for 1 year or more.5 of our patients were diagnosed with COVID-19 infection (10% of all patients). 2 of these five patients are actively using everolimus. Of those diagnosed with COVID-19, 3 are women and 2 are men.The average age of the patients is 50.08 (43-66). While 3 patients had mild illness (60%), 2 patients (40%) died. One of the deceased patients is female and one is male. The female patient had a history of using everolimus for breast cancer, while the male patient died at the age of 52 while actively using everolimus for thymoma. Conclusions: Everolimus is a MTOR inhibitor used in many malignancy treatments. In our study, we found that 10% of our patients had COVID infection and 2 of our patients died due to COVID-19. In the group that discontinued everolimus treatment for a year or more, 1 patient died due to COVID-19, and 1 patient in the group still receiving everolimus treatment. Studies with larger patient populations are needed to determine whether everolimus carries an additional risk of COVID-19 infection.
イリノテカン化学療法を受ける日本の患者におけるUGT1A1*28およびUGT1A1*6の遺伝子検査
Authors: Akiyama Y, Fujita K, Nagashima F, Yamamoto W, Endo H, Sunakawa Y, Yamashita K, Ishida H, Mizuno K, Araki K, Ichikawa W, Miya T, Narabayashi M, Kawara K, Sugiyama M, Hirose T, Ando Y, Sasaki Y
Journal: Annals of Oncology (2008)
Prostate cancer intensive, non-cross reactive therapy (PRINT) for CRPC: Interim analysis of efficacy endpoints.
Authors: Bobby Chi-Hung Liaw, Xiaobo Zhong, Che-Kai Tsao, Richard Lorne Bakst, Robert Stewart, Richard Stock, Matt D. Galsky, William K. Oh
Journal: Journal of Clinical Oncology (2021)

e17027 Background: The standard mCRPC treatment paradigm, with sequential single agents administered until resistance, may be limited due to heterogenous tumors comprised of clones differentially sensitive to available therapies. An alternative approach involves rapid cycling of non-cross resistant therapies in an attempt to efficiently eradicate sensitive clones, mitigate resistance, and minimize toxicity. Methods: Patients with mCRPC received 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month study regimen, patients continued ADT alone. The primary endpoint is time to progression (TTP). A sample size of 33 patients will provide 90% power for a one-sided test at the 5% level to detect increase in TTP compared with historical control. Secondary endpoints include PSA response (&gt;90%, &gt;50%) with each module, and changes to alkaline phosphatase levels. Results: From 3/2017 to 11/2020, 40 mCRPC patients were enrolled. As of the data cut-off of 1/03/2021, 31 patients have completed the 9-month study regimen and are evaluable for TTP analysis. With a median follow up of 20.7 months, the median time to PSA progression is 3.8 months (95%CI; 2.1-6.3 mo). PSA declines &gt;90% from baseline was achieved in 35.5% after module 1, 41.9% after module 2, 58.1% after module 3. Of the patients with bone metastasis and elevated alkaline phosphatase levels at baseline (9/31), 78% had normalization of alkaline phosphatase upon completion of study regimen. Five of 31 patients (16%) were able to be maintained on ADT alone for over a year during the post-study surveillance period: three patients were subsequently restarted on a mCRPC agent at time of disease progression (14.4 mo, 17.0 mo, 24.8 mo), two patients demonstrate sustained disease control and remain on ADT alone (16.3+ mo, 21.5+ mo). Shared baseline clinical features of the 5 patients with prolonged control include PSA of &lt;10 ng/mL and normal alkaline phosphatase levels (&lt; 126 IU/L); Gleason score and presence of bone and nodal metastases varied. Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross resistant regimen is feasible and a subset of patients achieve prolonged disease control on ADT alone after completion of study treatment. Rapid cycling of available CRPC therapies may eliminate castration-resistant clones in a subset of patients, a concept warranting further preclinical and clinical evaluation. Clinical trial information: NCT02903160. [Table: see text]
Preliminary data from QUILT 3.055: A phase 2 multi-cohort study of N803 (IL-15 superagonist) in combination with checkpoint inhibitors (CPI).
Authors: John M. Wrangle, Mark M. Awad, Firas Benyamine Badin, Mark P Rubinstein, Paul Bhar, Chad Garner, Sandeep K. Reddy, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2021)

2596 Background: There is currently a paucity of treatment options for checkpoint relapsed patients who have had an initial response but subsequently progress. N803, a novel IgG1 Fc-engineered IL-15-complexed protein may rescue checkpoint activity in a checkpoint independent manner via its selective enhancement of natural killer cell (NK) and CD8+ T cell number and function, without stimulation of T regs and MDSCs. Methods: QUILT 3.055, (NCT03228667) a phase 2b study of N803 plus investigator choice CPI in 11 tumor types: NSCLC, SCLC, Urothelial carcinoma, HNSCC, Merkel cell carcinoma, Melanoma (single PD-1/PD-L1 CPI or w/ ipilimumab), Renal cell carcinoma (RCC), Gastric cancer, Cervical cancer, Hepatocellular carcinoma, Microsatellite instability-high (MSI-H)/ mismatch repair deficient (dMMR) solid tumors, with a heterogeneous mix of prior therapies. We present interim data for 135 patients treated with CPI alone or in combination with chemotherapy as their most recent prior therapy. Trial inclusion required investigator assessed progression on last line of therapy, patients had either CR with relapse or partial response or stable disease for 6 months with progression as their most recent result of checkpoint therapy. Patients with hyperprogression or best initial response of progression were excluded. Subjects received N803 15mck/kg SC q 3 weeks in combination with the same checkpoint inhibitor on which they had their most recent progression. Results: Preliminary data from 135 patients (60% NSCLC) with treatment with checkpoint and N-803 following progression on the same checkpoint show CR 0%, PR 8%, Stable Disease 51%, Progression 29%, response unevaluable 12% to date. A PR or SD was seen in all subgroups. Median PFS 3.9 months (95% CI: 2.6,5.0). Median OS 13.8 months (95% CI: 11.8, 16.3) N-803 is well tolerated with grade 1-2 common N-803 treatment related adverse events (TRAE) were injection site reaction (68%), chills (32%) fatigue (26%), pyrexia (26%), flu-like illness (14%), nausea (12%) and no other individual AE &gt; 10%. Grade 3 N-803 TRAE were 12% but no individual grade 3 AEs were greater than 5%. Conclusions: N803 demonstrates low toxicity in patients previously treated with CPI and promising efficacy of cessation of progression and induction of response and durable stable disease in patients who had previously progressed on a CPI containing regimen in multiple tumor types and different CPIs. Clinical trial information: NCT03228667.
Development of a Novel Class of Microtubule Destabilizing Agents with Selectivity Against Diffuse Large B-Cell Lymphoma (DLBCL) with B-Cell Receptor (BCR) Activation
Authors: Benet Pera Gresely, Francisco de Asís Balaguer, Mariano Gonzalo Cardenas, Maria Victoria Revuelta, Maria Nieves Calvo Vidal, Rossella Marullo, Nahuel Zamponi, Ildefonso Ismael Rodriguez Rivera, Yong Ai, Joseph Fraser Glickman, Isabel Barasoain, Fernando Díaz, Ari Melnick, Fengtian Xue, Leandro Cerchietti
Journal: Blood (2017)
Real-world safety and medication use of second-line (2L) 5-fluorouracil (5-FU)–based regimens among patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: George P. Kim, Paul Cockrum, Andy Surinach, Shu Wang, Zev A. Wainberg
Journal: Journal of Clinical Oncology (2021)

e16248 Background: Chemotherapy-related adverse events (AEs) can negatively impact the treatment of pts. Managing and preventing these toxicities often require additional medications. This study examined the proportion of pts with mPDAC treated with 5-FU–based regimens in 2L who experienced AEs during treatment, and the proportion who received medication to manage those AEs. Methods: Data were extracted for pts diagnosed with mPDAC who initiated 2L treatment Jan 2016 to Aug 2020 from the Flatiron Health database. Pts included were treated with FOLFIRINOX (FFX), FOLFOX, FOLFIRI, or liposomal irinotecan (nal-IRI). The occurrence of grade 3 (G3) and grade 4 (G4) neutropenia and G3/G4 thrombocytopenia were determined using lab results and the grading criteria from the CTCAE v4.03. The occurrence of diarrhea and nausea/vomiting (N/V) were identified via ICD-10-CM codes. The use of atropine and granulocyte colony stimulating factor (G-CSF) during treatment was assessed. Duration of therapy (DOT) was assessed for each regimen. Descriptive statistics for AEs, medication use, and DOT were reported. Results: Of the 825 eligible pts, 29.0% (n=239) received FFX, 40.2% (n=332) received regimens containing nal-IRI, 24.0% (n=198) received FOLFOX, and 6.8% (n=56) received FOLFIRI. The median DOT (IQR) was 15.1 weeks (wks) (7.1 – 30.1), 12.9 wks (6.0 – 24.8), 11 wks (6.4 – 24.0), and 12.7 wks (8.3 – 24.6) for pts who received FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 thrombocytopenia (&lt;50,000/mm 3 ) presented in 9.6%, 2.4%, 8.1%, and 14.3% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 neutropenia (&lt;1000/mm 3 ) presented in 22.6%, 12.3%, 14.6%, and 19.6% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. The median (Q1-Q3) cumulative dose of the G-CSF pegfilgrastim was 18mg (12 – 45), 18mg (12 – 48), 24mg (12 – 36), and 30mg (13 – 48) for pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. Atropine use was higher in pts treated with FFX and FOLFIRI (90.8% and 94.6%, respectively) than for pts treated with nal-IRI (75.6%). The full study results are reported in the table. Conclusions: In this study of AEs among pts with mPDAC treated in 2L, pts who received liposomal irinotecan had the lowest proportion of thrombocytopenia and neutropenia. Diarrhea was similar across the cohorts despite the high proportion of use in atropine for pts treated with FFX and FOLFIRI.[Table: see text]
Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study)
Authors: Maarten C. C. M. Hulshof, Elisabeth D. Geijsen, Tom Rozema, Vera Oppedijk, Jeroen Buijsen, Karen J. Neelis, Joost J. M. E. Nuyttens, Maurice J. C. van der Sangen, Paul M. Jeene, Jannie G. Reinders, Mark I. van Berge Henegouwen, Adriana Thano, Jeanin E. van Hooft, Hanneke W. M. van Laarhoven, Ate van der Gaast
Journal: Journal of Clinical Oncology (2021)

To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer.Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival.Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively (P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively (P = .15).In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.
Telehealth: Reducing or increasing cancer care disparities?
Authors: Patricia Jewett, Rachel I. Vogel, Rahel G. Ghebre, Arpit Rao, Jane Yuet Ching Hui, Helen Parsons, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2021)

1582 Background: During the COVID-19 pandemic, most cancer care in the United States transitioned to telehealth (phone or video visits) to reduce infection risks for patients and providers. Telehealth may simplify care logistics (e.g. reduce travel and waiting times), but it may also unintentionally exacerbate existing disparities in healthcare utilization by race/ethnicity, age, or rural/urban status. As telehealth will likely continue long-term, we examined telehealth use at a comprehensive cancer center during the COVID-19 pandemic across patient populations with established disparities in cancer treatment and outcomes. Methods: We retrospectively reviewed telehealth visits from March until December 2020 among individuals diagnosed with cancer at the University of Minnesota Masonic Cancer Center (MCC). We used Chi-squared tests and GEE logistic regression to compare video vs. phone visits by age, urban/rural status, and race/ethnicity (American Indian / American Native [AIAN], Asian, Non-Hispanic Black/African American [NH Black/AA], Hispanic, Multiple, Native Hawaiian / Pacific Islander [NHPI], NH White). Results: Over the study period, 42,171 telehealth visits were performed with 11,097 patients at the MCC. Patients had a mean age of 62.7±13.9 years; 59.2% were female; 88.7% lived in urban areas; 90.0% of patients were NH White, 4.4% NH Black/AA, 3.0% Asian, 1.5% Hispanic, 0.8% AIAN, 0.3% of multiple races, and 0.1% NHPI. The most common cancer sites were breast (24.1%), hematological (21.0%), gynecologic (10.0%), and lung (8.4%). NH White individuals were more likely (53.9%) to use video than AIAN (39.7%), Black/AA (37.8%), or NHPI individuals (34.9%). Video use was less common among rural (45.3%) than urban (53.7%; p&lt;.0001) residents, and among individuals aged 65 or older (45.2%) vs. younger than 65 (59.5%; p&lt;.0001). In a logistic regression, adjusted for continuous age and urban/rural status, all race/ethnic groups except Multiple were less likely to use video than NH White individuals (vs. phone; Table). Conclusions: Our findings underscore disparities in telehealth use for cancer care across historically underserved populations. Future research should evaluate potential underlying contributors to these disparities such as technology access, internet capability, and fear of discrimination. Additional research is also needed to determine whether video vs. phone visits affect cancer outcomes, therefore indicating true disparity.[Table: see text]
BrainStorm: A brain metastases research platform to tackle the challenge of central nervous system (CNS) metastases in solid tumors (Oncodistinct 006).
Authors: Nuria Kotecki, Maria Alice B Franzoi, Marianne Paesmans, Florian Clatot, Edith Borcoman, Anthony Goncalves, Philippe Barthelemy, Claire Cheymol, Jean-Pierre Delord, Andrea Gombos, Vincent Vanhaudenarde, Stephane Holbrechts, Francois P. Duhoux, Jean-Luc Re Canon, Lore Decoster, Hannelore denys, Caroline Duhem, Nadège Kindt, Ahmad Awada
Journal: Journal of Clinical Oncology (2021)

TPS2066 Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text]