tbuckley/cabot-search huggingface dataset:
Neratinib efficacy in a subgroup of patients with <i>EGFR</i> exon 18<i>-</i>mutant non-small cell lung cancer (NSCLC) and central nervous system (CNS) involvement: Findings from the SUMMIT basket trial.
Authors: Jonathan Wade Goldman, Santiago Viteri Ramirez, Amit Mahipal, Jennifer Marie Marie Suga, Lisa DeFazio Eli, Alshad S. Lalani, Richard Bryce, Feng Xu, Naisargee Shah, Fairooz Kabbinavar, Valentina Boni, Barbara B. Haley
Journal: Journal of Clinical Oncology (2021)

9068 Background: The phase 2 SUMMIT basket trial (NCT01953926) demonstrated efficacy of neratinib in patients with EGFR exon 18-mutant NSCLC [Boni et al. WCLC 2020]. Neratinib also has documented activity in HER2+ metastatic breast cancer with CNS metastases [Saura et al. SABCS 2020 &amp; J Clin Oncol 2020]. Here we report neratinib efficacy in a subgroup of patients with EGFR exon 18-mutant NSCLC and CNS involvement from SUMMIT. Methods: Patients with EGFR exon 18-mutant NSCLC were treated with single-agent neratinib (240 mg po daily). Prior EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and checkpoint inhibitors (IO) were allowed. Patients with stable, asymptomatic CNS metastasis were enrolled. Study endpoints: objective response rate (ORR) at week 8 (±1 week); ORR (RECIST 1.1 confirmed); duration of response (DOR); clinical benefit rate (CBR); progression-free survival (PFS); safety; biomarkers. Results: Baseline characteristics of 11 patients with EGFR exon 18-mutant NSCLC: median age 67 (range 56–83) years; ECOG PS 0/1 (45%/55%). Prior lines of therapies: 2 (range 1–3): EGFR TKIs (91%); chemotherapy (55%); IO (27%). 3/11 patients had baseline CNS metastasis and received radiation 8–22 months prior to study enrollment. Best CNS response in these 3 patients was stable disease with overall individual PFS of 1.9 (censored), 6.9 and 9.1 months and OS of 2.6 (censored), 17.7 (censored), and 17.9 months. Efficacy is summarized in Table. Efficacy summary: TKI-pretreated EGFR exon 18-mutant NSCLC cohort receiving neratinib monotherapy. Conclusions: Activity of single-agent neratinib was observed in prior TKI-exposed patients with EGFR exon 18-mutant NSCLC. Despite the small sample size of only 3 patients with baseline CNS metastases, findings suggest a potential role for neratinib as a systemic treatment option for patients with NSCLC and difficult-to-treat uncommon mutations with CNS involvement. The SUMMIT trial continues to enroll patients with EGFR exon 18-mutant NSCLC. Clinical trial information: NCT01953926. [Table: see text]
Cancer-related outcomes in oncology patients admitted to physical rehabilitation facilities.
Authors: Julie Huang, Angela Ramdhanny, Alison Daly, Meredith Akerman, Marc Justin Braunstein
Journal: Journal of Clinical Oncology (2021)

e18643 Background: Admission to a physical rehabilitation facility (RF) can improve mobility and quality of life metrics in cancer patients, however, limited data exist on how these admissions impact cancer-related outcomes. We hypothesized that admissions to a RF following hospitalization delays cancer-directed treatment and increases mortality compared to those who are discharged home. Methods: A retrospective chart review identified oncology patients who were being treated with either intravenous or subcutaneous cancer-directed therapy between 2010-2020 and admitted to either a RF or home following hospitalization. Exclusion criteria were patients not on active cancer-directed treatment or going to hospice. Comparisons of RF vs. home were made using a chi-square test or Fisher’s exact test for categorical outcomes. Median days to next chemotherapy for each group were assessed with Kaplan-Meier/Product-Limit Estimates with a corresponding 95% confidence interval. Results: Of 189 patients, 24 were admitted to a RF and 165 went home. The median age of the study population was 65.6 years, with more males (66.7%) admitted to a RF vs. discharged home (49.7%), and both groups having &gt;50% advanced stage cancer; primarily GI malignancies (25.9%) (Table). There was a statistically significant increase in the percent of patients who experienced delays in the time to their next anticipated chemotherapy date in the RF group vs. home (70.8% vs. 30.3%, P&lt;0.0001), as well as median days to next chemotherapy (38.5 vs. 22, P&lt;0.007). 30-day readmission rates were higher in patients at a RF vs. home (50% vs 29%, P&lt;0.04). There were no significant differences in mortality comparing RF vs. home at 3, 6, or 12 months from the index inpatient hospitalization. Conclusions: Hospitalized oncology patients who were admitted to a RF had significant delays in cancer-directed therapy. Despite the smaller sample size of patients in a RF, their 30-day readmission rates were higher, suggesting a need to carefully select patients who can afford delays in cancer treatment.[Table: see text]
Pembrolizumab patient reported benefits: A perspective based on multiple tumors.
Authors: Elise Wu, Paivi H Miskala, Mohd Kashif Siddiqui, Pankaj Rai, Eva Hajdukova, Nathalie Erpelding, Jacqueline Vanderpuye-Orgle
Journal: Journal of Clinical Oncology (2021)

2650 Background: Pembrolizumab is a programmed death ligand receptor-1 (PD-L1) treatment indicated for multiple tumors. Patient-reported outcomes (PRO) benefit has only been reported at the tumor level, while a holistic review of PRO effects across tumor types has been missing. We performed a systematic review of PRO to assess the overall health-related quality of life (HRQoL) among cancer patients treated with pembrolizumab across multiple tumors. Methods: We systematically searched PRO evidence published from January 2014 to April 2020 across approved pembrolizumab indications using Embase, MEDLINE, and CENTRAL. Eligible studies were required to assess cancer patients treated with pembrolizumab (200 mg or 2mg/kg Q3W) and report PROs and/or HRQoL. The PRO evidence was summarized into three categories: short-term (≤Week 12), mid-term (Week 13-Week 24), and long-term (Week 25-Week 52). A clinically meaningful difference in HRQoL is defined as at least a 10 points improvement or deterioration relative to baseline; a change between ± 10 points is defined as stable. Results: We screened 1,262 citations, of which 16 publications reported EORTC QLQ-C30 data; 10 (9 trial-based studies; 1 observational study) of 16 publications reported global health status (GHS) mean change from baseline (CFB) across six indications. Within trial based studies in first-line setting (n=3 studies), the short-term, mid-term, and long-term GHS changes from baseline vary from 0.5 to 2.1, 1.2 to 8.4, and 1.6 to 2.5, respectively. For second-line plus setting (n=6 studies), GHS changes vary from -3.3 to 8.6, -1.0 to 10.9, and -0.9 to 9.2, respectively. Eight trial-based publications reported EORTC QLQ-C30 domain data as CFB. Short- or mid-term mean changes in functioning domain data showed improvement or stability in emotional, cognitive, role, and social functioning. Short-term deterioration in physical functioning was observed for 1 study, whereas physical functioning remained stable for other studies. For symptom domains, deterioration was not observed in any studies; mid-term improvement was reported by one study each in fatigue, dyspnea, and appetite loss; 2 studies reported mid-term improvement in pain. Conclusions: This is the first study that presented pembrolizumab PRO evidence at the product level. This study suggests that most pembrolizumab-treated patients maintained or improved HRQoL relative to baseline at pre-defined timepoints. This review's limitations include potential publication bias and lack of meta-analytic methods in reporting results. Nevertheless, these findings provide additional information about pembrolizumab's benefits to physicians and patients from a patient-centric perspective.
Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB).
Authors: Giuseppe Curigliano, Volkmar Mueller, Virginia F. Borges, Erika P. Hamilton, Sara A. Hurvitz, Sherene Loi, Rashmi Krishna Murthy, Alicia Frances Clare Okines, Elisavet Paplomata, David A. Cameron, Lisa A. Carey, Karen A. Gelmon, Gabriel N. Hortobagyi, Ian E. Krop, Sibylle Loibl, Mark D. Pegram, Dennis J. Slamon, Jorge Ramos, Chiyu Zhang, Eric P. Winer
Journal: Journal of Clinical Oncology (2021)

1043 Background: Tucatinib (TUC) is an oral tyrosine kinase inhibitor (TKI) highly specific for HER2. TUC is approved for use in combination with trastuzumab (T) and capecitabine (C) in patients (pts) with and without brain metastases (BM) who have received 1 or more prior anti-HER2–based regimens in the metastatic setting. In the primary analysis from the pivotal HER2CLIMB trial, the addition of TUC to T and C in pts with HER2+ metastatic breast cancer showed a statistically significant and clinically meaningful prolongation of progression-free (PFS) (HR = 0.54 [95% CI: 0.42, 0.71]; P &lt; 0.001) and overall survival (OS) (HR = 0.66 [95% CI: 0.50, 0.88]; P = 0.005) (Murthy, et al. NEJM 2020). TUC in combination with T and C was well tolerated with few discontinuations other than for disease progression. Based on these data, the protocol was amended for unblinding of sites to treatment assignment to allow for crossover from the placebo arm to receive TUC in combination with T and C. Methods: HER2CLIMB (NCT02614794) is a global, randomized, double-blind, placebo-controlled trial in pts with unresectable locally advanced or metastatic HER2+ breast cancer previously treated with T, pertuzumab, and T-emtansine (T-DM1), including pts with untreated, treated stable, or treated and progressing BM. Overall 612 pts were randomized 2:1 to receive TUC 300 mg BID or placebo, each in combination with T and C. Randomization was stratified by BM, ECOG performance status, and geographic region. Protocol prespecified analysis of OS, PFS (by investigator assessment) and safety in the total study population will be performed at approximately 2 years from the last patient randomized. Results: Updated Kaplan-Meier time-to-event analysis of OS and PFS with hazard ratios and 95% confidence intervals for TUC arm vs placebo arm will be presented overall, as well as for OS in the prespecified subgroups reported previously (Murthy, et al. NEJM 2020). Safety and tolerability assessments will include frequency of adverse events by severity, dose modifications and discontinuation of study medications. Conclusions: Conclusions will be presented in the presentation. Clinical trial information: NCT02614794 .
Prevalence of HER2 low in breast cancer subtypes using the VENTANA anti-HER2/neu (4B5) assay.
Authors: Marietta Scott, Michel Erminio Vandenberghe, Paul Scorer, Anne-Marie Boothman, Craig Barker
Journal: Journal of Clinical Oncology (2021)

1021 Background: Breast cancer patients with HER2 low expression by immunohistochemistry (IHC), defined as IHC1+ or IHC2+ without gene amplification (ISH-) do not respond to conventional anti-HER2 therapies such as trastuzumab or pertuzumab. The HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) showed efficacy in late line HER2-overexpressing patients, with some responses in patients with low HER2 expression. Two of the market leading IHC IVDs are Dako Herceptest and Ventana 4B5. T-DXd is being investigated in HER2 low patients as determined by the VENTANA anti-HER2/neu (4B5) assay in the phase III DESTINY-Breast04 study. There is a paucity of information on prevalence of IHC1+/2+ in different breast cancer subtypes, which this study aims to address. Methods: HER2 status was calculated from 3750 consecutive primary or metastatic breast cancer patient samples successfully stained using the 4B5 assay and scored locally according to ASCO/CAP 2018 guidelines. Samples were obtained from 3 anatomic pathology labs that support networks of US community hospitals. 500 additional breast cancer samples, pre-selected to include a range of IHC staining (concordance cohort), were stained with both 4B5 and HercepTest (Dako/Agilent) and scored (IHC0, IHC1+, IHC2+, IHC3+) at a central laboratory. Results: Prevalence of HER2 categories in 3750 consecutive breast cancer samples is presented in the table below. &gt;50% of estrogen-receptor positive (ER+ve) and progesterone receptor positive (PR+ve) subtypes are HER2 low. In the 500 sample concordance cohort, 28.0% were IHC1+/2+ using the 4B5 assay compared with 11.6% using HercepTest. HercepTest identified IHC1+/2+ staining in 21.6% [95%CI:15.1,29.4] of the patients classified as IHC1+/2+ by 4B5. 98.3% [95%CI: 96.2, 99.5] of samples IHC0 by 4B5 were also IHC0 by Herceptest. Conclusions: HER2 IHC1+/2+ (ISH-) by Ventana 4B5 represent a significant proportion of breast cancer patients and more than 50% of ER+ve and PR+ve subtypes. The 4B5 assay classed several patients as IHC1+/2+ that are IHC0 by Herceptest, but almost all patients IHC0 by 4B5 were also IHC0 by Herceptest.[Table: see text]
Risk factors for 30-day readmissions in patients with tumor lysis syndrome and solid malignancies: Analysis from the National Readmission Database.
Authors: Estefania Gauto, Miguel Salazar, Shristi Upadhyay, Binav Baral, Maryam Zia, Trilok Shrivastava, Juan Adolfo Cattoni
Journal: Journal of Clinical Oncology (2021)

e18863 Background: Tumor lysis syndrome (TLS) is a well-known potentially fatal complication of chemotherapy and an oncologic emergency. It is most prevalent in hematologic malignancies, but there are case reports and clinical series of occurrence after the treatment of solid tumors. Hospital readmissions are indicators of quality of care and cost control. We aim to look at the prevalence of readmissions after an initial episode of TLS in patients with solid malignancies and their financial burden on the United States healthcare system. Methods: We conducted a retrospective analysis of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an initial “index” admission of TLS (ICD10 code E88.3) with a concomitant diagnosis of solid malignancy. We aimed to identify the 30-day readmission rate, mortality, healthcare-related utilization resources, and independent predictors of readmission by performing a COX regression analysis. Results: A total of 874 patients with solid tumors were admitted with TLS in 2017. The 30-day readmission rate was 20.4%. The main causes for readmission were sepsis, recurrent malignant lesions, metastasis to CNS, bleeding, acute kidney failure (AKI). Compared to initial admissions, readmitted patients were less likely to have acute kidney failure (AKI) (64.6% vs 30.8%; P &lt; 0.01), less likely to require mechanical ventilation (17.9% vs 5.7%; P &lt; 0.01), less likely to suffer shock (7.3% vs 2.3%; P = 0.03) and ileus (4.8% vs 0.7%; P = 0.04). Readmission was associated with higher in-hospital mortality rate (0.1% vs. 1.5%; P &lt; 0.01), more likely to have private insurance (29.9% vs 36.1%; P &lt; 0.01), and more likely to be discharged home (26.2% vs 36.8%; P &lt; 0.01). The total health care in-hospital economic burden of readmission was $14.9 million in total charges to patients and $4 million in total costs for hospitals. Independent predictors of readmission were prolonged length of stay (during index admission), tobacco abuse, VTE, thrombocytopenia, and admission to an urban hospital. We identified the following preventive factors for readmission: radiation therapy, admission to a smaller hospital, total parenteral nutrition during the index admission and a primary gynecologic malignancy. Conclusions: Readmissions after TLS in patients with solid malignancy are associated with a higher in-hospital mortality rate and pose an increased health care burden. We identified risk factors that, if targeted, could lead to reducing readmissions, health care burden, and patient morbidity.
Results of a German survey among patients with gynecological malignancies during the COVID-19 pandemic.
Authors: Desislava Dimitrova, Robert Armbrust, Sara Nasser, Seyma Boz, Dario Zocholl, Emelina Fucaraccio, Marion Kiechle, Jalid Sehouli
Journal: Journal of Clinical Oncology (2021)

e13533 Background: The COVID-19 pandemic has had an immense impact on health care systems und social life. Due to limited resources, a rearrangement in medical care has been necessary in many countries. Strict rules of social distancing and postponing of medical appointments has brought major changes. At the beginning of the COVID-19 pandemic, in March 2020, several studies reflecting patient perception of cancer care modification were performed. Currently, there are still limited data on patient perception concerning changes in cancer treatment, their willingness to receive a COVID-19 vaccine, and their acceptance of social life restrictions. We initiated a multicentre prospective anonymous survey among patients with gynecological cancer to gather information about the current therapy situation and the impact of their treatment and social life. We will report the first preliminary results of 108 patients. Methods: We performed a survey among patients with gynecological cancer, who received treatment or were in follow-up at Charité Campus Virchow Klinikum between October and December 2020. The paper form questionnaire included three sections in which social background, current disease status, and patient perception of the COVID-19 implications on cancer care and social life were evaluated. Results: We included 108 patients. The median age of the participants was 59. The majority of the participants had ovarian cancer (69.4 %) and 70 % were under current cancer treatment. Almost 65 % were willing to receive a COVID-19 vaccine. More than 50 % reported anxiety and fear during the last 2 weeks. Only 16.2 % were more afraid of a COVID-19 infection than their cancer disease. Despite uncertainty of the COVID-19 pandemic, most patients fear tumour progression more than a COVID-19 infection. The cancer treatment appointments were altered in a small number of patients (9.4 %). Testing of COVID-19 was performed in 73 % of the participants. The acceptance of social measures was high; 87 % keeping social distance and over 90 % wearing a mask. Conclusions: Despite major challenges in cancer care due to the COVID-19 pandemic for the majority of the patients, the access to cancer treatment was less affected and the acceptance of prevention measures was high. Anxiety and fear was experienced by more than 50 %. The psychological effects of the COVID-19 pandemic should be further explored. The survey underscores the high need of information regarding COVID-19 and cancer.
Serum neutrophil/lymphocyte ratio as a potential predictor of treatment response for immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.
Authors: Jian He, Zhiqiang Mo, Qicong Mai, Xiaoming Chen
Journal: Journal of Clinical Oncology (2021)

e16156 Background: Neutrophil to lymphocyte ratio (NLR) has been shown to associate with tumor progression. The present study was to investigate the role of NLR on predicting the treatment response for immune checkpoint inhibitors (ICIs) therapy in patients with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 81 patients received ICIs for advanced HCC from January 2017 to July 2019. We analyzed whether pre- and first 3 weeks post- treatment serum NLR level was associated with ICIs outcome. Results: In this study, the pre-treatment NLR level ranged from 0.64 to 14.93 among 81 patients. The cut-off level of NLR was set as the median value of 2.79. The objective response rate (ORR) in the patients with NLR＜2.79 (low NLR) was 25.0%, which was significantly better than that of patients with NLR ≥2.79 (high NLR) (7.3%, P ＝0.03). Compared to patients with high NLR, patients with low NLR exhibited significantly longer median progression-free survival (PFS) (3.7 vs 3.0 months, P ＝0.004) and median overall survival (OS) (10.3 vs 7.5 months, P ＝0.001). Multivariate analysis revealed high NLR was an independent unfavourable prognostic factor for PFS (hazard ratio [HR] = 1.857, 95% confidence interval [CI] = 1.093-3.154; P = 0.022) and OS (HR = 2.267, 95% CI = 1.221-4.207; P = 0.009). For the patients with high pre-treatment NLR level, ICIs outcome was stratified more clearly by first 3 weeks post- treatment NLR level. Conclusions: The pre- and first 3 weeks post- treatment serum NLR level could be considered as a predictive factor of treatment response for ICIs in patients with advanced HCC.
A phase 1, first in human study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in subjects with HER2 overexpressing solid tumors.
Authors: Joshua Bauml, Natalie Sophia Grover, Amy Ronczka, Daniel Cushing, Michael Klichinsky, Debora Barton, Elizabeth Claire Dees
Journal: Journal of Clinical Oncology (2021)

TPS2660 Background: Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but not in those with solid tumors. Macrophages are actively recruited into, and abundantly present in the solid tumor microenvironment (sTME). Tumor- associated macrophages typically evince immunosuppressive behavior, but when engineered to be proinflammatory, may be an ideal vector to administer adoptive cellular therapy in solid tumors. Furthermore, insertion of a CAR confers on the macrophages the ability to selectively recognize and phagocytose antigen overexpressing cancer cells. Additionally, CAR macrophages reprogram the sTME and present neoantigens to T cells, leading to epitope spreading and immune memory. Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in many cancers, including but not limited to breast and gastroesophageal cancers (Table). CT-0508 is a cell product comprised of autologous monocyte-derived pro-inflammatory macrophages expressing an anti-HER2 CAR. Pre-clinical studies have shown that CT-0508 induced targeted cancer cell phagocytosis while sparing normal cells, decreased tumor burden and prolonged survival in relevant models. CT-0508 cells were safe and effective in a semi-immunocompetent mouse model of human HER2 overexpressing ovarian cancer. Methods: This is a FIH phase 1 study to evaluate safety, tolerability, cell manufacturing feasibility, trafficking, and preliminary evidence of efficacy of investigational product CT-0508 in approximately 18 subjects with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2 who have failed available therapies including anti-HER2 therapies when indicated. Filgrastim will be used to mobilize autologous hematopoietic progenitor cells for monocyte collection by apheresis. The CT-0508 CAR macrophage product will be manufactured, prepared and cryopreserved from mobilized peripheral blood monocytes. The study is enrolling Group 1 subjects, who will receive CT-0508 infusion split over D1, 3 and 5. Subjects will be continually assessed for acute and cumulative toxicity. Dose limiting toxicities will be observed and addressed by a Safety Review Committee. Group 2 subjects will follow, and will receive the full CT-0508 infusion on D1. Pre and post treatment biopsies and blood samples will be collected to investigate correlates of trafficking, persistence, TME modulation, immune response and safety. Clinical trial information: NCT04660929. [Table: see text]