tbuckley/cabot-search huggingface dataset:
Real-world utilization of EGFR TKI therapies and treatment outcomes in patients with advanced EGFR-sensitizing mutation-positive NSCLC.
Authors: Gregory J. Riely, Christine Marie Lovly, Carlo GM Messina, Stefanie Bienert, Kimberly Alexander, William Pao, Shrujal Baxi, Robert Charles Doebele
Journal: Journal of Clinical Oncology (2019)

9062 Background: In patients with advanced non-small cell lung cancer (aNSCLC) with non-squamous histology, treatment guidelines recommend molecular testing for EGFR mutations and first-line (1L) EGFR tyrosine kinase inhibitors (TKIs) in those with sensitizing EGFR mutations. We investigated real-world treatment regimens and outcomes in aNSCLC patients with EGFR-sensitizing mutations from US community oncology clinics. Methods: The Flatiron Health electronic health record-derived database contains deidentified data from &gt; 55,000 aNSCLC patients. Our retrospective cohort included patients diagnosed from Jan-2014 to Mar-2018 who had a positive EGFR test prior to initiation of 1L therapy. Patients with EGFR T790M mutations were excluded. Demographics, clinical characteristics, treatment and survival outcomes were compared between patients receiving 1L EGFR TKIs vs other 1L anti-cancer therapies. Minimum follow-up after initiation of 1L therapy was 4 months. Results: 23,321 patients had non-squamous or NOS histology. Of those, 1107 had sensitizing EGFR mutations detected prior to 1L treatment (median age 70 years, 67% women, 58% Caucasian). 910 (82%) received EGFR TKIs and 197 (18%) received other 1L therapies (including chemotherapy, immunotherapy and anti-VEGF therapy). 2L treatment data were available for 519 patients: 317 (61%) received EGFR TKIs and 202 (39%) received other therapies. In the 1L setting, median treatment duration was longer for patients receiving EGFR TKIs than for those receiving other therapies (8 vs. 4 months, unadjusted HR 1.70; 95% CI 1.45–1.99; p &lt; 0.0001). Median overall survival (OS) was not affected by the type of 1L treatment (21 months vs 20 months, p = 0.55). Conclusions: Real-world examination of treatment patterns and outcomes in US community oncology clinics showed that nearly 20% of aNSCLC patients with non-squamous or NOS histology and EGFR sensitizing mutations prior to initiation of 1L therapy did not receive 1L EGFR TKIs. In those who did, guideline-concordant use of EGFR TKIs was associated with longer 1L treatment duration but no improvement in OS, supporting the generalizability of results from randomized clinical trials.
Pembrolizumab (pembro) for patients (pts) with high-risk (HR) non–muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG): Updated follow-up from KEYNOTE-057.
Authors: Ronald De Wit, Girish S. Kulkarni, Edward M. Uchio, Laurence Eliot Miles Krieger, Joost L. Boormans, Mathieu Roumiguié, Eric A. Singer, Dean F. Bajorin, Ashish M. Kamat, Petros Grivas, Ho Kyung Seo, Hiroyuki Nishiyama, Badrinath R. Konety, Kijoeng Nam, Ekta Kapadia, Tara L. Frenkl, Arjun Vasant Balar
Journal: Journal of Clinical Oncology (2019)

4530 Background: Upregulation of the PD-1 pathway has been observed in BCG-unresponsive NMIBC, suggesting that pembro may be beneficial. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study (NCT02625961); updated results for pts with carcinoma in situ (CIS) with or without papillary tumors (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary tumors who received adequate BCG therapy and were unable/refused to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts who developed HR NMIBC or progressive disease during treatment were required to discontinue. Key end points were complete response rate (CRR), duration of response, and safety. Results: 102 pts (median age, 73 years; CIS alone, 63.7%; median number of prior BCG instillations, 12) had enrolled in cohort A as of enrollment cutoff. Median (range) duration of follow-up was 15.8 mo (4.6-28.2) ; 3-mo CRR was 40.2% (95% CI, 30.6-50.4) by central assessment. Among 41 pts who had CR at 3 mo, median CR duration was 12.7 mo (range, 0+ to 20.5+ mo); 75.4% had a CR duration ≥ 6 mo; 52.6% had a CR duration ≥12 mo (Kaplan-Meier method); 24 pts (58.5%) maintained CR at last follow-up, and 15 (36.6%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle-invasive or metastatic disease. CRR was 44.6% for pts with CIS alone (n = 65), 41.7% for CIS with T1 tumors (n = 12), and 28.0% for CIS with high-grade Ta tumors (n = 25). Treatment-related adverse events (AEs) occurred in 66 (64.7%) pts; most frequent (≥10%) were pruritus (10.8%), diarrhea (10.8%), and fatigue (9.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.7%) pts. Immune-mediated AEs occurred in 19 (18.6%) pts. Conclusions: Pembro continued to show encouraging antitumor activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial information: NCT02625961.
The impact of systemic treatment on brain metastasis in patients with non-small-cell lung cancer: A retrospective nationwide population-based cohort study.
Authors: Yoon Ho Ko, Ji Hyung Hong, Der Sheng Sun, Hye Sung Won, Seok Yun Kang, Jung Soo Lee, Hyun Woo Lee
Journal: Journal of Clinical Oncology (2019)

e20572 Background: We performed a large-scale, retrospective, nationwide, cohort study of the incidence of brain metastasis in patients with advanced non-small-cell lung cancer (NSCLC) according to the systemic treatment administered. Methods: The data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011 to November 30, 2016. Of the 29,224 patients newly diagnosed with stage IIIB or IV NSCLC who received first-line cytotoxic chemotherapy (CC group) or targeted therapy (TT group), 22,508 patients without brain metastasis were analyzed. Results: In total, 1,131 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7 ± 0.6% vs. 3.8 ± 0.3%; 3-year: 17.2 ± 0.7% vs. 5.0 ± 0.3%, respectively; P &lt; 0.001), despite the higher rate of brain metastasis in the CC group at &lt; 3 years after diagnosis. Younger age, female sex, living in a rural area, anticoagulant use, and first-line TT (relative risk, 2.17 ± 0.03; 95% confidence interval, 1.92–2.50, P &lt; 0.0001) retained significant associations with subsequent brain metastasis after adjusting for all variables. Conclusions: In the Korean population, the overall cumulative incidence of brain metastasis was significantly higher in patients in the TT group than in those in the CC group; the former could be regarded as having mutations in the EGFR or ALK gene.
Impact of dual anti-HER2 therapy on pathologic complete response rate in breast cancer in a minority-enriched population.
Authors: Jenny Jing Li, Hsiao Ching Li, Ang Gao, Samira K. Syed, Nisha Unni, Navid Sadeghi
Journal: Journal of Clinical Oncology (2019)

e18111 Background: The addition of pertuzumab (P) to a neoadjuvant trastuzumab (H) plus chemotherapy combination has been shown to significantly improve the pathologic complete response rate (pCR) in localized HER2+ breast cancer; however, minorities have been under-represented in these trials. Racial/ethnic disparities have also been shown to affect outcomes of cancer treatment. This study is aimed to assess the impact of neoadjuvant dual HER2-blockade in an unselected minority-enriched population. Methods: A retrospective chart review was conducted of women with stage I to III HER2+ breast cancer who received neoadjuvant treatment between 2007 and 2017 at an academic institution and its affiliated safety net health system. Data on stage, chemotherapy, race/ethnicity, site of therapy (academic vs safety net hospital), and hormone receptor status were collected. All patients underwent surgery after completion of neoadjuvant chemotherapy. pCR was defined as ypT0/is, ypN0. Chi-squared test and univariate/multivariate logistic regression were used for statistical analysis. Results: The study population included 261 women with the following race/ethnic distribution: 37.7% Non-Hispanic Whites, 34.6% Hispanics, 20.6% Blacks, and 7% other racial/ethnic origin. Ninety-five patients (36%) received chemotherapy-H vs 166 patients (64%) received chemotherapy-HP. Patients at the safety net health system had higher stage at diagnosis compared to the academic site. Site of care and race/ethnicity did not impact the choice of neoadjuvant treatment. The pCR rate was significantly higher for the chemotherapy-HP group (55.4%) compared to the chemotherapy-H group (34.7%) (p = 0.001). There was no association between race/ethnicity, or site of treatment (academic vs safety net), and the probability of achieving pCR. Multivariate analysis showed only dual anti-HER2 therapy (OR: 2.67, CI: 1.55-4.59, p = 0.0004) and hormone-receptor negative status (OR: 2.18, CI: 1.30-3.67, p = 0.0031) to correlate with pCR. Conclusions: Neoadjuvant dual anti-HER2 therapy was more likely to result in a pCR in our minority enriched population. Our data also suggests the combination of chemotherapy-HP confers similar benefit irrespective of race/ethnicity or site of care.
Basket of baskets (BoB): A modular, open label, phase II, multicenter study to evaluate targeted agents in molecularly selected populations with advanced solid tumors.
Authors: Irene Brana, Christophe Massard, Richard D. Baird, Frans Opdam, Richard F. Schlenk, Luigi De Petris, Claudio Vernieri, Elena Chavarria, Elena Garralda, Ruud van der Noll, Ana Vivancos, Lodewyk F. A. Wessels, Jose-Ezequiel Martin, David Tamborero, Rodrigo Dienstmann, Gerrit A. Meijer, Susana Muñoz, Alejandro Piris-Giménez, Fabien Calvo, Jordi Rodon
Journal: Journal of Clinical Oncology (2019)

TPS3151 Background: Basket trials with targeted agents can show high response rates for tumors with specific molecular profiles, granting extension of the label of some drugs. In other cases, study results were disappointing, likely due to the rarity of molecular alterations, limits in trial design and the difficulties in applying molecular tumor profiling in the clinical setting. Methods: Basket of Baskets (BoB), NCT03767075, aims to bridge the gap between Academic Genomics and clinical applications (ready-to market multi-marker Companion Diagnostics) by providing a sustainable and adaptable (to new technologies, markers, and therapeutic agents) platform for co-development of drug/companion diagnostic. BoB is a novel platform trial from Cancer Core Europe, a recently established sustainable European network for innovative cancer research. This protocol has two parts: (1) Part A includes a molecular profiling program for subjects with advanced solid tumors (iPROFILER), a variant annotation tool, and a molecular tumor board to select the most appropriate treatment. It also enables testing/developing companion diagnostics linked with the therapeutic part (part B). (2) Part B includes iBASKET, a modular multi-arm basket trial for subjects with tumors harboing selected molecular alterations. Each module is focused on a certain molecular pathway or on certain molecular alterations that may confer sensitivity to the study drug or study drug combination evaluated in that module/arm. The current version of iBASKET (Module 1- Atezolizumab in genomically-selected patients) is open for enrollment for patients with advanced neoplasms bearing one of the following alterations: Arm 1A: BRCA1 or BRCA2; Arm 1B: MLH1, MSH2, MSH6, PMS2; Arm 1C: POLE, POLD1 mutations; Arm 1D: hypermutated tumors; Arm 1E: other mutations in DNA-repair genes; Arm 1F: PDL1 gene amplification. All patients enrolled in Module 1 will receive single-agent atezolizumab. New Modules for genomically selected populations can be added through amendments. Our final aim is to achieve drug repurposing of treatments, co-develop multi-marker companion diagnostics and a large database of knowledge in Precision Medicine. Clinical trial information: NCT03767075.
Why now for a Series on gender equality, norms, and health?
Authors: Gary L Darmstadt, Lori Heise, Geeta Rao Gupta, Sarah Henry, Beniamino Cislaghi, Margaret E Greene, Sarah Hawkes, Katherine Hay, Jody Heymann, Jeni Klugman, Jessica K Levy, Anita Raj, Ann M Weber
Journal: The Lancet (2019)
Impact of antibiotic use on clinical outcomes in patients with urothelial cancer receiving a programmed death protein 1 or programmed death ligand 1 (anti-PD-1/L1) antibody.
Authors: Chana Weinstock, Virginia Ellen Maher, Laura L Fernandes, Shenghui Tang, Sundeep Agrawal, Michael Holman Brave, Yang-Min Ning, Harpreet Singh, Daniel L. Suzman, James Xu, Kirsten B. Goldberg, Rajeshwari Sridhara, Amna Ibrahim, Marc Robert Theoret, Julia A. Beaver, Richard Pazdur
Journal: Journal of Clinical Oncology (2019)

4557 Background: Previous data has suggested that patients treated with anti-PD-1/L1 antibodies who receive antibiotics during their therapy might have dramatically decreased progression-free and overall survival 1,2 . This has clinical implications for management of patients with suspected bacterial infection while on treatment with these agents. We assessed the relationship between antibiotic use and tumor response rate, progression-free survival, and overall survival in a large dataset of patients with urothelial cancer treated with anti-PD-1/L1 antibodies. Methods: We examined seven trials that led to drug approval and which included 1747 patients with metastatic or locally advanced urothelial cancer treated with an anti-PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy and two enrolled patients who were cisplatin-ineligible. Six were single arm trials and one was a randomized controlled trial whose control arm is not included in these analyses. Concomitant medication datasets were searched for systemic antibiotic used by each patient while on treatment. Results: Overall, 51% of patients (n=892) were exposed to antibiotics (ABX+) and 49% (n=855) were not exposed (ABX-). In these exploratory analyses, small numeric differences in OS, PFS, and ORR were seen in ABX+ vs. ABX- patients. Median OS was 9.23 vs. 9.86 months, median PFS was 105 vs 101 days, and ORR was 20% vs. 21% in ABX+ vs. ABX- patients, respectively. Conclusions: Patients who were treated with antibiotics while on therapy with an anti-PD-1/L1 antibody for urothelial cancer had similar outcomes to those who were not treated with antibiotics. Numeric differences in outcomes were not significant and did not duplicate previous analysis demonstrating a median OS that was doubled in ABX- patients 1 . Our exploratory analyses do not appear to demonstrate a clear need for practitioners to avoid antibiotic use in patients treated with PD-1/L1 agents for fear of significantly impacting clinical outcomes. References: 1) Tinsley et. al., ASCO annual meeting 2018, abstract 3010 2) Routy et. al., Science 05 Jan 2018: Vol. 359, Issue 6371. [Table: see text]
AB1103 NEUROLOGICAL IMPAIRMENT DURING SARCOIDOSIS
Authors: sameh sayhi, Rim Dhahri, Najah Boussetta, Bilel Arfaoui, Feida Laajili, Bassem Louzir, Hajer Derbali, Linda Mrisa, Ridha Mrisa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> <h3>Objectives</h3> To describe neurological impairment characteristics in sarcoidosis. <h3>Methods</h3> This was a descriptive and retrospective study including 65 patients with sarcoidosis, followed in the departments of internal medicine and neurology at the Military Hospital of Tunis over a period of 20 years from 1997 to 2017. <h3>Results</h3> A total of 65 patient files have been selected, of which 38 have neurological involvement. Thirty-eight patients met the inclusion criteria for Neurosarcoidosis. According to Zajicek's criteria, the diagnosis of neurosarcoidosis was certain in 2 cases, probable in 18 cases and possible in 18 cases. Neurological disorders were symptomatic in 58.5% of the studied population. Neurological signs were inaugural in 9 patients (14% of cases). A central neurological involvement was demonstrated in 33 patients (86.8%), the peripheral nervous system was affected in 5 patients (13.1%), and cranial nerve involvement was found in 10 patients (26.3%).%). Ten patients have had both central and peripheral impairement. Neurological involvement was significantly associated with cardiac, renal extra-thoracic, ophthalmologic, articular and cutaneous involvement (p &lt;0.05) Genotyping of the conversion enzyme and HLA typing did not show any particular pattern of neurosarcoidosis in comparison with patients without neurological signs. <h3>Conclusion</h3> Neurological impairement was frequently observed in our series. It was also significantly associated with multivisceral involvement without particular genetic pattern. <h3>Disclosure of Interests</h3> None declared
Interleukin-2 boosts local and abscopal antitumor effect of radiotherapy combined with anti-PD-1: A translational research from clinical radio-memory effect.
Authors: Dawei Chen, Xinyu Song, Jinbo Yue, Ligang Xing, Jinming Yu
Journal: Journal of Clinical Oncology (2019)

e14244 Background: Preclinical and clinical studies have shown that prior receipt of radiotherapy enhances antitumor immune responses, a phenomenon we call the “radio-memory effect.” However, all of the evidence regarding this effect to date comes from work with anti-PD-1 or anti-PD-L1 inhibitors. Here we explore whether this effect also occurs with other forms of immune therapy, specifically interleukin-2 (IL-2). If so, whether this triple combination therapy could produce synergetic anti-tumor effect. Methods: 1. Clinical work: we retrospectively assessed outcomes in patients with malignant peritoneal effusion (MPE) who had previously received radiotherapy for colon or rectum cancer within 18 months before the intrapleural infusion of IL-2 or cisplatin. All patients received intrapleural infusion of IL-2 or cisplatin, and most had had several cycles of standard chemotherapy for colon or rectum cancer. 2. Translational work: MC38 cell line (5×10 6 ) was subcutaneously inoculated into the right lower extremity of C57/BL mice to construct a primary tumor model. Six days later, MC38 cell line (1×10 6 ) was subcutaneously inoculated into the left lower limb to construct a second tumor model. The main research is as follows: To explore the optimal radiation dose and fraction for radiotherapy; Whether the addition of IL-2 will further enhance the efficacy of radiotherapy combined with anti-PD-1; To explore the optimal combination model of radiation, anti-PD-1 and IL-2; Whether the addition of IL-2 will increase the abscopal effect produced by radiotherapy and anti-PD-1. Results: 1. We identified 3,747 patients with MPE (median age 66 years [range 24–81)) treated at one of several institutions from August 2009 through May 2016; 412 patients had been treated with IL-2 and 592 with cisplatin and had survived for at least 3 months afterward. 2. Hypofractionated radiotherapy (12Gy × 2) combined with IL-2 is better; IL-2 will enhance the efficacy of radiotherapy combined with anti-PD-1; IL-2 and anti-PD-1 followed by radiotherapy might maximize the anti-tumor effect; IL-2 might increase the abscopal effect produced by radiotherapy combined with anti-PD-1. Conclusions: We speculate that previous radiotherapy could enhance the efficacy of IL-2 and the anti-tumor effect produced by radiotherapy combined with anti-PD-1 could be enhanced by IL-2. The “radio-memory” effect could be beneficial in future studies.
Abstract 23079: Clinical Outcomes of Transcatheter Mitral Valve Replacement for Degenerated Mitral Bioprostheses (Mitral Valve-in-Valve) and Surgical Rings (Mitral Valve-in-Ring) in the United States: Data From the STS/ACC/TVT Registry
Authors: Mayra Guerrero, Dee Dee D Wang, Sreenkanth Vemulapalli, Katelyn Xiang, Michael Salinger, Mackram Eleid, Adam Greenbaum, Susheel Kodali, Isaac George, Brian Whisenant, Ashish Pershad, Kenith Fang, Megan Coylewright, Pinak B Shah, Vinod Thourani, Vasilis Babaliaros, Carl Tommaso, Jorge Saucedo, Saibal Kar, Raj Makkar, Martin Leon, Charanjit Rihal, William O'Neill, Ted Feldman
Journal: Circulation (2017)

Introduction: Transcatheter mitral valve replacement (TMVR) using aortic transcatheter heart valves (THV) is developing as an alternative to surgery for patients with severe mitral valve disease due to degenerated mitral bioprostheses or failed surgical rings who are poor surgical candidates. Outcomes of off-label procedures in the United States are being collected in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry. A comprehensive analysis of mitral Valve-in-Valve (VIV) versus Valve-in-Ring (VIR) outcomes has not previously been performed. Objectives: To evaluate in-hospital and 30-day clinical outcomes of mitral VIV and VIR procedures in the United States. Methods: Retrospective analysis of data from the STS/ACC TVT Registry on patients who underwent mitral VIV or VIR procedures. Results: 587 patients underwent TMVR VIV (n=494) or VIR (n=93) procedures between January 2013 and December 2016 at 144 hospitals. Median age was 76 (VIV) and 73 (VIR) years, (p=0.024), 60.9% (VIV) and 44.1% (VIR) were female (p=0.003), median left ventricular ejection fraction was 55% in VIV and 50% in VIR (p &lt;0.001), and median STS score was 10.5% (VIV) and 9.2% (VIR), p=0.131. Transseptal access was utilized in 35% VIV and 46.2% VIR procedures, p=0.081. Procedural success was achieved in 74.4% of VIV and 57.8%VIR (p=0.239). Left ventricular outflow tract (LVOT) obstruction was more common in VIR (5.4%) vs VIV (0.06%), p=0.003. Post-procedure median mean mitral valve gradient was 4mmHg in both groups. 95.7% of VIV and 86% of VIR patients had post-procedure mitral regurgitation ≤1(+), p&lt;0.001. In-hospital mortality was 6.9% for VIV and 9.7% for VIR (p=0.343). 30-day mortality was 9% for VIV and 12% for VIR (p=0.387). At 30-day follow up, 85.6% of VIV and 77.7% of VIR patients were in New York Heart Association class I or II (p=0.398). Conclusions: TMVR VIV and VIR using aortic transcatheter heart valves in high surgical risk patients are associated with similar in-hospital and 30-day mortality and symptom benefit. LVOT obstruction post-TMVR and residual mitral regurgitation ≥2 (+) were more frequent in VIR procedures. The long-term effect of these procedures is not known and requires further evaluation.