tbuckley/cabot-search huggingface dataset:
A phase ib trial of assessing the safety and preliminary efficacy of a combination therapy of geptanolimab (GB 226) plus fruquintinib in patients with metastatic colorectal cancer (mCRC).
Authors: Yuxian Bai, Nong Xu, Shan An, Wenhui Chen, Chao Gao, Deyong Zhang
Journal: Journal of Clinical Oncology (2021)

e15551 Background: A combination of anti-vascular endothelial growth factor receptor(anti-VEGFR) and anti-programmed cell death-1/ligand 1 (PD-1/L1) may synergize with each other and lead to better anti-tumor efficacy. We aimed to assess the safety and preliminary efficacy of combination therapy with geptanolimab (GB226, a highly selective, fully human monoclonal antibody PD-1 mAb) plus fruquintinib (a VEGFR inhibitor) in previously treated metastatic colorectal cancer (mCRC) patients. Methods: In this phase Ib trial, we enrolled mCRC patients who had failed one or two standard therapies. Patients were given geptanolimab (3mg/kg every 2 weeks) and fruquintinib (once daily for 21 days on/7 days off with planned dose cohorts of 3mg, 4mg, and 5mg) on a 28-day cycle. A standard 3+3 design was employed to determine the primary endpoints of the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) based on dose-limiting toxicities (DLT). Secondary endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Results: By December 15, 2020, 15 patients were enrolled: 1 with MSI-H, 12 with MSS, and 2 with MS unknown. Ten out of 15 patients (66.7%) had received ≥2 previous lines of treatment including chemotherapy in combination with anti-EGFR (33.3%) or anti-VEGF (53.3%). Seven patients (46.7%) were found to have the PD-L1 combined positive score (CPS)≥1. Two DLTs (one patient with grade 3 ALT and AST elevation and one patient with grade 3 proteinuria) were identified in fruqintinib 5mg cohort (6 patients enrolled). No DLT was observed in either 3mg (3 patients enrolled) or 4mg (6 patients enrolled) cohorts. RP2D of this combination was identified as geptanolimab (3mg/kg, every 2 weeks) and fruquintinib (4mg, once daily for 21 days on/7 days off). In all evaluable patients, the overall ORR was 26.7% (4/15, 3 confirmed PR, 1 unconfirmed PR), and the ORR was 33.3% (2/6) in the RP2D group. The DCR for all evaluable patients was 80%, and the median PFS (mPFS) was 7.33 months (95% CI: 1.91 – NE). The median DOR and median OS was not reached at the data cut-off date. Among 12 patients with MSS, the ORR was 25.0% (3/12, 2 confirmed PR, 1 unconfirmed PR), DCR was 75% and mPFS was 5.45 months (95% CI: 1.84-9.66). All patients had at least 1 treatment related AE (TRAE). The common TRAE were proteinuria (46.7%), hypertension (46.7%), and elevated aspartate aminotransferase (40.0%). Grade 3 AEs were observed in 46.7% of patients and the most common grade 3 AE was hypertension (20.0%). No grade 4 and 5 TRAE was observed. Conclusions: The combination of geptanolimab and fruquintinib had manageable safety profiles and encouraging anti-tumor activity in mCRC patients. Clinical trial information: NCT03977090.
Phase 1 dose escalation study of MGC018, an anti-B7-H3 antibody-drug conjugate (ADC), in patients with advanced solid tumors.
Authors: Sekwon Jang, John D. Powderly, Alexander I. Spira, Ouiam Bakkacha, Deryk Loo, Gerry C. Bohac, Manish Sharma
Journal: Journal of Clinical Oncology (2021)

2631 Background: MGC018 is an investigational ADC with a duocarmycin payload linked to an anti-B7-H3 monoclonal antibody (mAb). B7-H3 is expressed on multiple solid tumors with limited normal tissue expression. It is hypothesized that MGC018 may exert activity against B7-H3-expressing tumors with an acceptable safety profile. Studies demonstrate that B7-H3 is a significant factor in progression and events of metastasis of multiple tumor types, including melanoma. Methods: This phase 1 study characterizes safety, maximum tolerated or maximum administered dose, pharmacokinetics, immunogenicity, and tumor response per RECIST v1.1 of MGC018 in a 3+3+3 dose escalation design in patients with advanced solid tumors. MGC018 was administered intravenously (IV) every 3 weeks. Results: The study enrolled 29 patients of multiple tumor types, which included 3 melanoma patients refractory to ≥2 prior lines of checkpoint therapy. The study completed 5 of 6 planned dose cohorts (0.5 mg/kg - 4 mg/kg) as of the data cutoff of 21 January 2021. The final cohort of 4 mg/kg has 3 patients with ongoing treatment and follow-up at the date of submission. Dosing MGC018 IV every 3 weeks resulted in minimal serum accumulation. At least 1 treatment emergent adverse event occurred in 29 patients (100.0%); most common (≥25%) were anemia, neutropenia, fatigue, hyperpigmentation, infusion related reaction, nausea, and palmar plantar erythrodysesthesia. Two dose-limiting toxicities occurred; one grade 4 neutropenia (2 mg/kg) and one grade 3 fatigue lasting 7 days (4 mg/kg). No febrile neutropenia was reported. The 3 melanoma patients had reductions in target lesion sum of 24.4%, 27.5%, and 35% (unconfirmed partial response) and remain on treatment as of the data cutoff. The recommended phase 2 dose was determined to be 3 mg/kg. Conclusions: Results to date demonstrate a manageable safety profile, with early evidence of clinical activity in pretreated metastatic melanoma. Cohort expansion is ongoing using a recommended phase 2 dose of 3 mg/kg IV every 3 weeks. The planned enrollment includes advanced metastatic castrate-resistant prostate cancer, melanoma, triple-negative breast cancer, and non-small cell lung cancer. Clinical trial information: NCT03729596.
Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study
Authors: Naveed Z. Janjua, Stanley Wong, Younathan Abdia, Dahn Jeong, Terri Buller-Taylor, Prince A. Adu, Hasina Samji, James Wilton, Margo Pearce, Zahid A. Butt, Amanda Yu, Mawuena Binka, Sofia Bartlett, Maria Alvarez, Mel Krajden
Journal: Journal of Hepatology (2021)
A clinical study of camrelizumab combined with chemotherapy and sequential apatinib in the second-line treatment of patients with advanced non-small cell lung cancer.
Authors: Yueyin Pan, Fengshou Jiang, Yingying Du, Yong Wang, Hu Liu, Zishu Wang, Hui Liang, Minghong Bi, Yiwei Yao
Journal: Journal of Clinical Oncology (2021)

e21051 Background: Camrelizumab combined with chemotherapy has shown a higher efficiency and survival benefit in clinical studies of the first-line treatment of lung cancer. This study aims to observe the clinical efficacy and safety of camrelizumab combined with chemotherapy and sequential apatinib in the second-line treatment of patients with advanced non-small cell lung cancer in a real environment. Methods: This is a prospective, open, multi-center observational study that includes advanced lung cancer that is older than 18 years old, regardless of gender, with an ECOG score of 0-1, and recurrence or failure after first-line platinum-based dual-drug chemotherapy patient. Results: As of January 25, 2021, a total of 18 patients were enrolled, of which 12 were female (66.67%), 11 patients had an ECOG PS score of 1 point (61.11%), and 15 patients were stage IV (83.33%), patients, 5 patients with tissue poorly differentiation (27.78%), 55.56% of the patients had undergone immunohistochemical testing, and 66.67% of the patients had become positive for the gene. A history of radiotherapy accounted for 11.11%, and a history of surgery on the primary lesion accounted for 27.78%. Previous first-line chemotherapy options were pemetrexed combined with cisplatin (22.22%), pemetrexed combined with lobaplatin (22.22%), pemetrexed combined with carboplatin (11.11%), bevacizumab combined with Platinum dual-drug regimen (38.89%); Among the 10 patients with evaluable efficacy, 0 had CR, 2 had PR, 6 had SD, and 2 had PD. The ORR reached 20.00% and the DCR reached 80.00%. The overall incidence of adverse reactions is low, and the medication process is safe and controllable. Conclusions: In this second-line clinical study of lung cancer, most of the patients enrolled were patients with poor PS scores and later stages, but the effectiveness and safety of carrelizumab in patients with advanced lung cancer were still confirmed. The dominant population and the combined treatment plan are still being studied. Clinical trial information: ChiCTR2000034597.
Adherence to abemaciclib in patients receiving antidiarrheal medicine.
Authors: Dipti Shah, Brooke Byrd, Elisea Avalos-Reyes, Amanda McCarthy, Olga S. Matlin, Rashmi Grover, Lucia Feczko
Journal: Journal of Clinical Oncology (2021)

e13016 Background: According to the National Cancer Institute, breast cancer is the most common form of cancer in the United States. Nearly 75% of patients with breast cancer have tumors that are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative. In 2017, the U.S. Food and Drug Administration (FDA) approved abemaciclib to treat adult patients who have HR+ and HER2- advanced or metastatic breast cancer. While the adverse events associated with abemaciclib have been well documented in clinical trials, it is unknown if adverse events, specifically diarrhea, impact adherence. The purpose of this study is to determine whether adherence to abemaciclib differs for patients who receive loperamide in welcome kits versus those who do not receive loperamide in welcome kits. Methods: This is a retrospective study of patients throughout the United States with HR+, HER2- breast cancer who received abemaciclib from a large specialty pharmacy from July 1, 2018 to December 31, 2019. Patients who received welcome kits (each welcome kit contains three boxes, each box contains ten 2mg tablets of loperamide) served as the intervention group; patients who did not receive welcome kits served as the standard of care group. Baseline characteristics of patients in each group were compared with t-tests for continuous data and the chi square test for categorical data. Medication possession ratio (MPR), dose reduction and dose omission rates in the first three months of taking abemaciclib were compared. Results: We identified 1,180 breast cancer patients who received abemaciclib. The intervention group had 317 patients, with an average age of 60.1 y (SD = 12.0); the control group had 863 members, with an average age of 58.7 y (SD = 11.8). Baseline characteristics did not differ significantly between groups, except for geography (p&lt;0.001), as seen in the table. There was no significant difference (p = 0.858) in mean MPR between the intervention and standard of care groups. There were no significant differences in dose reduction rates (p= 0.390) and dose omission rates (p = 0.872) within three months of starting abemaciclib. Conclusions: Our findings suggest that patients who receive loperamide in welcome kits do not have better adherence to abemaciclib therapy. In this study, both groups showed high adherence to therapy, suggesting that the standard of care group manages diarrhea just as effectively as the intervention group. A welcome kit with loperamide did not impact a patient’s adherence to abemaciclib therapy.[Table: see text]
COVID-related anxiety is prevalent and accurately reflects serious COVID risks in breast cancer patients.
Authors: Marisa C. Weiss, Stephanie Kjelstrom, Meghan Buckley, Adam Leitenberger, Melissa Jenkins, Katherine Aliano Ruiz, Alexandra Berk, Donna-Marie Manasseh, Sharon Larson
Journal: Journal of Clinical Oncology (2021)

12053 Background: A current cancer diagnosis is a risk factor for serious COVID-19 complications (CDC). In addition, the pandemic has caused major disruptions in medical care and support networks, resulting in treatment delays, limited access to doctors, worsening health disparities, social isolation; and driving higher utilization of telemedicine and online resources. Breastcancer.org has experienced a sustained surge of new and repeat users seeking urgent information and support. To better understand these unmet needs, we conducted a survey of the Breastcancer.org Community. Methods: Members of the Breastcancer.org Community were invited to complete a survey on the effects of the COVID-19 pandemic on their breast cancer care, including questions on demographics, comorbidities (including lung, heart, liver and kidney disease, asthma, diabetes, obesity, and other chronic health conditions); care delays, anxiety due to COVID-related care delays, use of telemedicine, and satisfaction with care during COVID. The survey was conducted between 4/27/2020-6/1/2020 using Survey Monkey. Results were tabulated and compared by chi square test. A p-value of 0.05 is considered significant. Data were analyzed using Stata 16.0 (Stata Corp., Inc, College Station, TX). Results: Our analysis included 568 breast cancer patients of whom 44% had ≥1 other comorbidities associated with serious COVID-19 complications (per CDC) and 37% had moderate to extreme anxiety about contracting COVID. This anxiety increased with the number of comorbidities (p=0.021), age (p=0.040), and with a current breast cancer diagnosis (p=0.011) (see table). Anxiety was significantly higher in those currently diagnosed, ≥65, or with ≥3 other comorbidities, compared to those diagnosed in the past, age &lt;44, or without other comorbidities. Conclusions: Our survey reveals that COVID-related anxiety is prevalent at any age regardless of overall health status, but it increased with the number of other comorbidities, older age, and a current breast cancer diagnosis. Thus, reported anxiety is proportional to the risk of developing serious complications from COVID. Current breast cancer patients of all ages—especially with other comorbidities—require emotional support, safe access to their providers, and prioritization for vaccination.[Table: see text]
Analysis of outcomes and disposition in hospitalized patients with head and neck cancer over 15 years.
Authors: Achuta Kumar Guddati, Takefumi Komiya
Journal: Journal of Clinical Oncology (2021)

e18021 Background: The care of hospitalized head and neck cancer patients often involves a multidisciplinary approach. The trends, outcomes and disposition in hospitalized patients with head and neck cancer in United States for the past two decades has not been well characterized. This retrospective study involves analysis of the demographics, outcomes and disposition of these patients and their trend over 15 years. The presence of medical comorbidities and the relationship to inpatient mortality was also studied. Methods: Hospitalization data from the National Inpatient Sample database was analyzed for the years: 2000 to 2014. Patients with head and neck cancer were identified using ICD-9 codes. Demographic features such as age, gender, race, geographical location, hospital size, hospital location, insurance etc. were analyzed. The trend of mortality was analyzed for the study period of 15 years. A sub-analysis of associated comorbidities was also performed in patients who have died during hospitalization. Univariate analysis was initially performed followed by multivariate analysis and logistic regression to identify risk factors associated with mortality. Results: An estimated 145,262 hospitalizations involving patients with head and neck cancer from 2000 to 2014 were studied and it showed a gradual yearly increment in hospitalization. 41% of the hospitalizations were in the 50-64 years age group. There was a 2:1 male preponderance. Caucasians constituted 60% followed by African Americans at 10%. A majority of the hospitalizations occurred in large sized hospitals and urban teaching hospitals. The mean length of stay was 6.4 days but 38% of the hospitalizations involving 2-5 days of stay. The inpatient mortality rate was 4.6% and it down trended over the past 15 years with statistical significance (p &lt; 0.05). Inpatient mortality was highest in the &gt; 80 years age group. Of note, inpatient mortality was equal between both the genders. Mortality was highest in the groups with a length of stay below 2 days and above 11 days. 58% of the discharges did not need any special services while 21% of the discharges involved home health care. The most common comorbidities were smoking and hypertension while &lt; 1% of morbid obesity was observed. Multivariate analysis showed malnutrition, ESRD, cirrhosis, stroke and CHF were significant risk factors (ORs: 1.6, 1.94, 2.18, 2.2 and 1.78 respectively). Conclusions: Mortality in hospitalized patients with head and neck cancer has improved over the past 15 years. Inpatient mortality was high in the very elderly and in female patients (compared to the male preponderance upon admission). Malnutrition, cardiac/liver/renal dysfunction and stroke were significant risk factors for inpatient mortality. Strategies to mitigate inpatient mortality in these patients need to factor the above risk factors during their in-hospital management.
A phase III clinical trial of adjuvant chemotherapy versus chemoimmunotherapy for stage IB-IIIA completely resected non-small cell lung cancer (NSCLC) patients nadim-adjuvant: New adjuvant trial of chemotherapy versus chemoimmunotherapy.
Authors: Virginia Calvo, Manuel Domine, Ivana Sullivan, Jose-Luis Gonzalez-Larriba, Ana Laura Ortega, Reyes Bernabé, Maria Angeles Sala, Begona Campos, Javier De Castro, Paloma Martín-Martorell, Joaquim Bosch-Barrera, Xabier Mielgo, Laia Vilà, Joaquin Casal, Silver Ros, Maite Martinez Aguillo, Airam Padilla, Sergio Sandiego, Jonathan Aires Machado, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2021)

TPS8581 Background: The results of current studies are considered acceptable evidence to support the hypothesis of efficacy of the proposed combination of immunotherapy with chemotherapy (CT-IO) in patients with NSCLC stages Ib-IIIA candidates for adjuvant treatment. Methods: This is an open-label, randomised, two-arm, phase III, multi-centre clinical trial. Primary objective and endpoint: The primary objective is disease free survival (DFS) defined time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time Sample size: 210 patients NSCLC stages Ib-IIIA (Experimental Arm (Adjuvant Chemotherapy-Inmunotherapy + maintenance adjuvant Inmunotherapy): 105 patients, Control Arm (Adjuvant Chemotherapy): 105 patients Treatment Patients randomised to the experimental arm will receive Nivolumab 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) as adjuvant treatment followed by maintenance adjuvant treatment for 6 cycles with Nivolumab 480 mg Q4W (+/- 3 days). Patients randomized to the control arm will receive Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) followed by 2 observation visits. Total trial duration: 6.5 years, 3.5 years of recruitment, 1 year of adjuvant treatment or observation and 2 years of follow up. The start date was January 2021. The estimated primary completion date is June 2027. Clinical trial information: NCT04564157.
Incidence and trend of Epstein-Barr virus-related cancer: A surveillance, epidemiology, and end results program based study.
Authors: Jiayi Shen, Meijuan Luo, LiTing Liu, Qiu-Yan Chen, Lin-Quan Tang, Hai-Qiang Mai
Journal: Journal of Clinical Oncology (2021)

10575 Background: Epstein-Barr virus (EBV) infection was highly prevalent, as was found in more than 90% of the adults globally. EBV infection has been found to be related with several types of cancer and classified as group 1 carcinogen by the International Agency for Research on Cancer. The association between EBV infection and malignancy was observed in Burkitt lymphoma (BL), Hodgkin lymphoma (HL), extranodal natural killer (NK)/T-cell lymphoma (NNKTL), gastric cancer (GC) and nasopharyngeal cancer (NPC). In this study, we aimed to analyze the incidence and the trend of incidence of these virus-related cancer and to identify whether the trend was similar between them. Methods: This was a retrospective analysis based on the data from Surveillance, Epidemiology, and End Results (18 registries, 2000-2017), which totally included 71,415 patients. EBV-related cancers were defined as BL, HL, NNKTL, GC and NPC. Age-adjusted incidence rates were displayed as per 100,000 persons. In terms of incidence trend, we calculated the average annual percent change (AAPC). AAPC was considered significantly different from 0 when the P-value was smaller than 0.05. The impact of the epidemiological and clinical characteristics on the incidence trend was estimated, with cancer type, histology, age, sex and race considered. Results: Incidence rates of EBV-related cancers were 6.68 per 100,000 persons in 2000 and 5.80 in 2017, of which the AAPC was -0.8 (95%CI, -1.1 - -0.5, P-value &lt; 0.001). (Table) Similar with EBV-related cancer as a whole, the APCCs of BL, HL and GC were statistically significantly smaller than 0, except that the APCCs of NNKTL and NPC were statistically significantly larger than 0 and not statistically significantly different from 0 respectively. The incidence of EBV-related cancer also decreased in mixed cellularity classical HL, nodular sclerosis classical HL, adenocarcinoma of GC, signet ring cell carcinoma in GC, undifferentiated carcinoma of NPC, squamous cell carcinoma of NPC, patients diagnosed at the age of 20-39 years old and 60-79 years old, male patients and race as white, black or Asian, but increased in classical HL, NOS, nodular lymphocyte predominant HL and non-keratinizing carcinoma of NPC. Conclusions: Incidence of EBV-related cancer decreased during 2000 and 2017, which was consistent in BL, HL and GC.[Table: see text]