tbuckley/cabot-search huggingface dataset:
A phase I study evaluating COM701 in patients with advanced solid tumors.
Authors: Drew W. Rasco, Daniel A. Vaena, Ryan J. Sullivan, Jason J. Luke, Adam ElNaggar, John Hunter, Adeboye H. Adewoye, Judy Olweny, Amita Patnaik, Erika Paige Hamilton
Journal: Journal of Clinical Oncology (2019)

TPS2657 Background: There is a high unmet medical need for the treatment (tx) of patients (pt) who are refractory to or relapse following tx with checkpoint inhibitors. Newer checkpoint therapies with novel mechanisms of action that can activate T cells and demonstrate antitumor activity in this pre-tx pt population are urgently needed. COM701 is a novel first-in-class humanized IgG4 monoclonal antibody that binds with high affinity to PVRIG (poliovirus receptor related immunoglobulin domain containing) blocking its interaction with its ligand, PVRL2. Both PVRIG and PVRL2 are part of the DNAM axis as are TIGIT and PD1. Inhibition of PVRIG leads to enhanced activation of T and NK cells, and PVRIG results in tumor growth inhibition in mouse tumor models. We hypothesize that COM701 will demonstrate antitumor activity in pts who are checkpoint inhibitor pre-tx. Methods: NCT03667716 is an ongoing open-label first-in-human phase 1 study in pts with advanced solid tumors. The initial part of this study (Arm A) will evaluate escalating doses of COM701 monotherapy IV Q3 weekly with single pt cohorts for the initial 4 and then 3+3 design. Key Inclusion Criteria: Age ≥18 yrs, histologically confirmed locally advanced/ metastatic solid malignancy and has exhausted available standard therapy, ECOG 0-1, prior anti-PD-1, anti-PD-L1, anti-CTLA-4, OX-40, CD137 permissible. Key Exclusion Criteria: Active autoimmune disease requiring systemic therapy in the last 2 years, symptomatic interstitial or inflammatory lung disease, untx or symptomatic central nervous system metastases. Primary objectives are safety and tolerability of COM701 as measured by the incidence of adverse events (AEs) and dose-limiting toxicities (21-day DLT window), pharmacokinetics of COM701, and to identify the maximum tolerated dose and/or the recommended dose for expansion. Secondary objectives are to characterize the immunogenicity and preliminary antitumor activity of COM701. Statistical Considerations: AEs graded as per CTCAE v4.03, responses as per RECIST v1.1. The analyses of all study objectives will be descriptive and hypothesis generating. No DLTs have been observed in the single pt cohorts. Assessment of pts enrolled into cohort 5 is ongoing at the time of this submission. Clinical trial information: NCT03667716.
Value of precision medicine in advanced NSCLC: Real-world outcomes associated with the use of companion diagnostics.
Authors: Ani John, Roma Shah, William Bruce Wong, Charles Schneider, Hamid H. Gari, Marliese Johnson
Journal: Journal of Clinical Oncology (2019)

e20015 Background: Five-year survival rates as low as 2.8% have been reported in patients with non-small cell lung cancer (NSCLC), highlighting the need for individualized diagnosis and treatment. Companion diagnostic testing (CDx) identifies patients with molecular targets likely to respond better to particular therapies; however, not all cancer patients receive CDx in the real-world setting. This study evaluated the clinical value of CDx in the real world with respect to overall survival among patients with non-squamous advanced (Stage IIIB/IV) NSCLC (aNSCLC). Methods: Patients were from the Flatiron Health electronic health-derived database, treated with systemic therapy, and diagnosed with aNSCLC between January 1, 2011 and May 31, 2018; those who received CDx with their first line of treatment were compared with those who did not. Logistic regression using components of the modified Lung Cancer Prognostic Index (LCPI; age, sex, stage, actionable mutation(s), smoking, respiratory comorbidity; Alexander et al. Br J Cancer. 2017) and other factors were used to predict characteristics associated with receiving CDx. Overall survival was evaluated using Kaplan-Meier analysis. Unadjusted and adjusted Cox proportional hazards regression models were used to evaluate the association between CDx and overall survival. Results: A total of 17,143 patients with aNSCLC (CDx, n = 14,389; no CDx, n = 2754) and a mean (SD) age at diagnosis of 67.2 (10.0) years (CDx, 67.1 [10.1]; no CDx, 67.5 [9.2]) were included. There were more nonsmokers in the CDx group (17.4%) than the no CDx group (5.5%). Patients who were female, diagnosed after 2014, receiving multiple lines of therapy or had advanced stage at diagnosis were more likely to receive CDx. Patients receiving CDx had decreased mortality risk (unadjusted HR [95% CI] = 0.54 [0.52-0.57]) and lived longer than those not receiving CDx (median survival = 14 vs 7 months). The significant reduction in mortality associated with CDx remained after adjusting for factors included in the modified LCPI (adjusted HR [95% CI] = 0.78 [0.75-0.82]) as well as a model without actionable mutations (adjusted HR [95% CI] = 0.70 [0.66-0.73]). Conclusions: Among patients with non-squamous aNSCLC, use of CDx was associated with reduced risk of mortality compared with no CDx.
The selective personalized radioimmunotherapy for locally advanced NSCLC trial (SPRINT).
Authors: Nitin Ohri, Haiying Cheng, Shruti Jolly, Shirish M. Gadgeel, Benjamin Thomas Cooper, Elaine Shum, Balazs Halmos
Journal: Journal of Clinical Oncology (2019)

TPS8571 Background: Concurrent chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC) can cause significant toxicities, and disease recurrence after treatment is common. We previously demonstrated that a dose-painted radiotherapy approach provides excellent local disease control and has a favorable toxicity profile. Consolidation immunotherapy was recently shown to improve outcomes after chemoradiotherapy for LA-NSCLC, and pembrolizumab monotherapy is now a standard of care for patients with advanced high PD-L1-positive NSCLC. We hypothesize that dose-painted thoracic radiotherapy and immunotherapy without chemotherapy will be safe and effective for the treatment of biomarker-selected patients with LA-NSCLC. Methods: Patients with a new diagnosis of unresectable stage II or stage III NSCLC and performance status 0-1 will be enrolled on this phase II trial at one of three participating institutions. Twenty-five subjects with PD-L1 Tumor Proportion Score (TPS) of at least 50% will receive three cycles of induction pembrolizumab (200 mg every 3 weeks). Subjects then receive 20 fractions of dose-painted radiotherapy, where lesions with metabolic tumor volume exceeding 20 cc on FDG-PET receive a dose of 55 Gy, while smaller lesions receive a dose of 48 Gy. Subjects then receive 12 additional cycles of pembrolizumab. The primary endpoint is progression-free survival one year following study enrollment, which we hypothesize will be achieved for at least 65% of study subjects. Other endpoints include overall survival, distant metastasis-free survival, freedom from intrathoracic disease progression, adverse events, patient-reported outcomes, and physical activity metrics captured using wearable devices. In addition, we will explore markers of immune activation as prognostic factors. Approximately 38 patients with PD-L1 TPS below 50% will receive standard chemoradiotherapy and adjuvant therapy to serve as a contemporary comparison cohort. SPRINT is an innovative biomarker-driven study that explores a paradigm shift in the local and systemic therapy used to treat LA-NSCLC. This trial opened in August of 2018, and 5 subjects have been enrolled to date. Clinical trial information: NCT03523702.
Prospective study of germline and somatic alterations for early onset lung cancer patients (EOLUNG MASTER protocol).
Authors: Maria Jove, Mireia Gausachs, Joaquim Bosch-Barrera, Enric Carcereny Costa, Alex Teule, Angel Izquierdo, Matilde Navarro, Ramon Palmero, Noelia Vilariño, Jose Carlos Ruffinelli, Elia Sais, Teresa Moran, Anna Estival, Claudia Fina, Joan Brunet, Gabriel Capella, Conxi Lazaro, Ernest Nadal
Journal: Journal of Clinical Oncology (2019)

TPS9122 Background: Lung cancer (LC) is a rare disease among young adults. Polymorphisms in genes involved in carcinogenic metabolism of tobacco and/or xenobiotic metabolism have been identified in those patients. The growing use of next generation sequencing (NGS) unravelled germline mutations in genes associated with hereditary cancer in patients with LC. However, germline DNA mutations have not been systematically studied in young adults with LC. Early onset LC patients are likely to harbor actionable somatic mutations. Broad hybrid NGS can identify actionable genomic alterations in LC patients deemed driver negative by routine molecular analysis. Trial Design: This is a multicentre, prospective, single-cohort study to determine whether young patients with LC harbor germline mutations and to evaluate the impact of NGS using Foundation One platform on the therapeutic options and overall survival for this specific patient population. Major inclusion criteria: 1) patients already or newly diagnosed of non-small cell lung cancer at any stage at age &lt; 51; 2) to have sufficient tumor sample to perform standard molecular diagnosis ( EGFR/ALK/ROS1/BRAF); 3) to provide written informed consent for the study. Methods: After signing the informed consent form, family history of cancer and smoking history will be collected and a peripheral blood sample will be obtained. Germline targeted sequencing will be carried out in our centre using a customized hereditary cancer panel (I2HCP) of 136 genes designed to cover the coding exons and intron-exon boundaries of genes associated with moderate or high risk of hereditary cancer. Patients with clinical criteria for hereditary cancer or harboring pathogenic or probably pathogenic germline alteration will be referred to the genetic counselling unit. Patients will follow the usual clinical pathway for biomarker analysis and in case of remaining tumour material it will be used for conducting comprehensive genomic profiling through Foundation One platform. When tumour material available will not be sufficient to perform NGS, a tumour re-biopsy will be considered. Enrolment begun on June 2018 and, to date, a total of 41 patients have been included in the study.
Elevated plasma cell-free DNA copy number variations to predict survival for cancer patient with spinal metastasis.
Authors: Su Chen, Minglei Yang, Nanzhe Zhong, Qian Ziliang, Jian Jiao, Yasong Xiao, Dongjie Jiang, Zhenhua Zhou, Tianzhen Wang, Yan Lou, Wei Xu, Wei Wan, Zhipeng Wu, Cheng Yang, Wei Wei, Tielong Liu, Jian Zhao, Haifeng Wei, Xinghai Yang, Jianru Xiao
Journal: Journal of Clinical Oncology (2019)

e14522 Background: Approximately 70% of patients with cancer have evidence of spinal metastatic disease at the time of their deaths. The spinal column is the most common location among osseous sites for metastatic deposits. Expected overall survival is the major determinant of treatments for those ones suffering from intractable pain, neurologic deficits, and even paralysis. We sought to evaluate copy number variations (CNV) in spinal metastatic cancer via cfDNA and determine if CNV is associated with prognosis and treatment decision. Methods: In this study, 314 patients with pathologically confirmed spinal metastatic cancers were recruited since November 2015. 314 plasma samples were sent to low-coverage genome-wide sequencing of cfDNA from plasma followed by a customized bioinformatics workflow UCAD. Tokuhashi score was also evaluated for each patient before surgery. Statistical correlation with clinical index like prognosis was estimated. Results: 280 evaluable data were collected (34 samples failed Quality Control). The median follow-up time is 276 days. 114 (40.7%) patients died during follow up till December the 25th, 2018. Elevated CNVs was found in 109 (38.9%) patients, including 9(69.2%) head&amp;neck, 15(46.9%) liver and gallbladder, 27(44.3%) lung, 7(38.9%) breast, 2(28.6%) prostate, 5(19.2%) thyroid cancer, 4 (10.5%) kidney and 20(40.0%) cancer with unknown primary site. Further analyses showed that patients with elevated CNVs were found with worse survival. The median overall survival (OS) was 298 (95% CI: 258-422) days, as compared with those low-CNVs status with median OS 657 (95% CI:433-NA) days (Hazard ratio = 3.73 [95% CI: 2.22-6.27], P &lt; 0.01). Especially for patients with low Tokuhashi score (≤8) who have the predictive survival less than 6 months, CNVs score distinguish those well-prognosis patients with median OS 433 (95% CI: 308-NA) days from the worse survival group with median OS 285(95% CI:243-348) days (Hazard ratio = 2.42 [95% CI:1.38-4.25], P = 0.013). Conclusions: We present the largest cfDNA genomic characterization of spinal metastatic cancers. Specific CNVs features are enriched in spinal metastasis cancers with different primary sites. Elevated CNVs in plasma cfDNA is significantly associated with worse survival in a large spinal metastatic cancer cohort. This demonstrates that cfDNA CNVs could be a useful marker in estimating the survival time of spinal metastasis cancer patients for whom the outcome is mainly dependent on the selection of proper treatment.
Cancer survivors’ challenges with ostomy appliances and self-management.
Authors: Virginia Sun, Octavio Bojorquez, Sabreen Raza, Marcia Grant, Mark C Hornbrook, Robert S. Krouse
Journal: Journal of Clinical Oncology (2019)

e23091 Background: Ostomies adversely affect health-related quality of life among cancer survivors. Survivors and their families must engage in ostomy self-management, make substantial behavior changes, and adjust to the consequences of their condition. We explored long-term cancer survivors’ challenges with ostomy appliances and ostomy self-management. Methods: Pooled qualitative data from two studies were used. These included 1) written responses from long-term (≥5 years) rectal cancer survivors describing their greatest challenges with ostomy appliances and associated repercussions; and 2) intervention session notes and greatest challenge responses from an ongoing RCT of a telehealth intervention with ostomy survivors. Using content analysis, several coauthors reviewed all responses related to ostomy wafers/appliances and self-management techniques, and coded each by theme. The themes were reviewed and agreed upon by the research team. Counts were tallied for each theme based on the number of times they were mentioned by respondents. Results: Eight themes emerged: bleeding, pain, leakage, skin problems/irritation/rash, wafer-related issues, materials getting under the wafer, time needed to care for ostomy, and solutions to clean the stoma. Collectively, the eight themes were mentioned 106 times by respondents. Overall, the most commonly mentioned ostomy appliance problem was leakage (27%), followed by skin problems (20%), and pain (14%). For these common problems, respondents described challenges with successfully fitting the wafer to prevent leakages, poor wafer adherence to the skin area surrounding the stoma, allergic reactions to adhesives, and painful sores around the stoma site. Respondents described how their anxiety related to leakage, odor, and/or skin irritation greatly inhibited their social activities and self-confidence with ostomy self-management. Conclusions: Cancer survivors living with an ostomy experience multiple obstacles with ostomy appliances and self-management. These obstacles undermine their ability to gain confidence in caring for their ostomy. Interventions to improve self-management and self-efficacy may ease the psychological and social burden of living with an ostomy.
The safety and tolerability of PD-1/PDL-1 inhibitors in hematologic malignancies: A meta-analysis.
Authors: Phyo Thazin Myint, Faisal Ali, Taha Alrifai, Zimu Gong, Phoo Pwint Nandar, Kelley Elizabeth Kozma
Journal: Journal of Clinical Oncology (2019)

e14131 Background: The safety of programmed death receptor and ligand-1 (PD-1/PDL-1) inhibitors in hematologic cancers is not well-defined. We conducted a meta-analysis to investigate their safety. Methods: Pubmed &amp; Cochrane databases were searched from 1968-2018. Full-text articles of clinical trials reporting treatment-related adverse events (AE) of PD-1/PDL-1 inhibitors in hematologic cancers were included. Incidences of all-grade and high-grade (≥grade 3) AEs were pooled and generated with a 95% confidence interval (CI) using a random effect model on STATA. Results: Eight studies (5 nivolumab &amp; 3 pembrolizumab) were identified, with 703 patients and the median age of 34. Six studies were done in patients with relapsed/refractory (R/R) classical Hodgkin Lymphoma, one in R/R diffuse large B-cell lymphoma and one in combined hematologic cancers. There were 1092 total AEs, with a pooled high grade AEs rate of 13% (95% CI 9-17%). High-grade AEs (HAE) are summarized in the Table. Lipase elevation was the most common HAE for nivolumab (pooled incidence of 13%; 95% CI 6-23%), whereas leukopenia was the most common HAE reported with pembrolizumab use (pooled incidence of 36%; 95% CI 10-65%) There were 47 treatment discontinuation due to treatment-related AE. For Nivolumab, there was one treatment-related death (of a heavily pretreated patient) due to fatal pneumonitis. Conclusions: PD-1/PDL-1 inhibitors are well-tolerated in hematologic malignancies with a favorable risk of adverse events and very low treatment-related mortality. The HAE profile of Nivolumab differs from Pembrolizumab, and future studies should assess this heterogeneity further. [Table: see text]
Follow-up of cancer patients at the Colorectal Multidisciplinary Clinic: The University of the Philippines - Philippine General Hospital (UP-PGH) experience.
Authors: Frederic Ivan Leong Ting, Danielle Benedict Leoncio Sacdalan, Josephine Anne Lucero Sacdalan, Dennis Lee Sacdalan
Journal: Journal of Clinical Oncology (2019)

e18022 Background: The University of the Philippines - Philippine General Hospital (UP-PGH) Colorectal Multidisciplinary Team is composed of colorectal surgeons, radiation oncologists, and medical oncologists tasked with the care of patients with colon and rectal cancers in a multidisciplinary clinic. Patients that have been lost to follow-up after initial work-up and treatment return later with more advanced disease if at all they come back for treatment. This is a concern because cancers of the colon and rectum are potentially curable if addressed in a timely manner by patient and physician. Moreover, aggressive follow-up of potentially curable colon and rectal cancers has been shown to improve patient outcomes. Identifying factors that contribute to poor patient follow-up will allow the team to design strategies that will lead to more patients completing treatment. This study aimed to identify the different factors that influence follow-up among Filipino cancer patients presenting at the UP-PGH Colorectal multidisciplinary clinic. Methods: This is a 6 month prospective cross-sectional pilot study where a questionnaire was designed to evaluate patient views regarding factors that contribute to continued follow-up as well as factors associated with poor follow-up at the colorectal multidisciplinary clinic. Patients were allowed to state multiple factors as they see fit. Descriptive statistics were employed in the analysis of data. Results: Of the 97 responders, 39 (40%) patients identified belief in the effectiveness of the treatment and trust in their physicians, 33 (34%) stated adequacy of family support , and 31 (32%) noted affordability of treatment as factors contributing to patient follow-up. In contrast, 44 (45%) patients identified financial constraints, and 7 (7%) stated the far distance of their home to the treatment center as potential causes of poor follow-up. Other potential causes of poor follow-up identified were fear and anxiety about treatment, intolerable side-effects, and long lines at the clinic -all with 2 (2%) responses each. Conclusions: Healthcare decisions in the Philippines are affected by an interplay of factors. This study has identified belief in treatment efficacy, trust in their attending physician, financial factors, and clinic accessibility as influencing continued patient follow-up. Future endeavors may be directed towards these factors to improve follow-up and care at the colorectal multidisciplinary clinic.
HIV associated hepatocellular cancer (HCC) in an inner-city minority population.
Authors: V V Pavan Kedar Mukthinuthalapati, Aakash Putta, Muhammad Zain Farooq, Kunnal Batra, Paul G. Rubinstein, Shweta Gupta
Journal: Journal of Clinical Oncology (2019)

e15680 Background: The Highly Active Anti-Retroviral Therapy (HAART) era has seen a rise in the incidence of non-AIDs defining cancers. This study was undertaken to study the characteristics associated with HIV+ HCC in an inner-city minority population. Methods: Patients with diagnosis of HCC since January 2011 until December 2018 were identified from our hospital’s electronic medical database using ICD-9/ICD-10 codes. Charts were retrospectively screened to confirm diagnosis of HCC and identify HIV+ patients. HIV+ HCC were compared to HIV- cohort from 2011 to 2016. Statistical analysis was done using the chi-square and t-test. Results: A total of 14 HIV+ HCCs were identified and compared to 239 HIV- HCC (Table 1). All HIV+ HCC were men (100%) with 86% African Americans (AA) (p &lt; 0.05). HIV+ HCC were more likely to be HCV+, HBV+ and less likely to have history of alcoholism. Seventy-nine percent HIV+ HCC were Child-Pugh A at diagnosis compared to 35% in HIV- HCC. The median years between diagnosis of HIV and HCC was 18. All 14 HIV+ HCC (100%) were on HAART at the time of HCC diagnosis with viral load (available for 12) undetectable in 10 (83%) and &lt; 100 copies/mL in 2 (17%). The average CD4 count at HCC diagnosis was 258 cells/µL with 10 (71%) having CD4 counts &gt; 200 cells/µL. HCC was multifocal in 71% HIV+ compared to 49% of HIV- patients. AFP levels were &lt; 20 ng/mL for 50% of the HIV+ HCC patients. There were 43% BCLC B and no BCLC D patients in HIV+ HCC compared to 17% and 24% in HIV- (p &lt; 0.05 for both). 67% HIV+ BCLC Stage C patients died within 20 weeks of HCC diagnosis. Conclusions: HIV+ HCC is predominantly AA, exclusively male disease in our inner-city population. Compared to other studies showing HIV+ HCC to be younger than the HIV- patients, our HIV+ patients were similar in age to the HIV- cohort. HIV+ HCC is more multifocal with early mortality despite early BCLC stage.. Studies are needed to investigate if frequent HCC screening may be needed in HIV+ patients with HCV/HBV co-infection.[Table: see text]