tbuckley/cabot-search huggingface dataset:
Measuring the long-term “tail of curve” survival benefits in oncology trials: A comparison of the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale.
Authors: Louis Everest, Monica Shah, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2019)

2585 Background: Recently, anti-cancer agents have generated excitement due to their capacity to preserve long-term survival in some patients, represented by a “tail of the survival curve”. However, as traditional measures of clinical benefit may not accurately capture long-term survival, amendments to various valuation frameworks have been proposed to capture this benefit. The purpose of this study was to determine how frequently immune checkpoint inhibitor vs. non-immune checkpoint inhibitor anti-cancer agents, displayed trends of long-term survival, as defined by the American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), as well as to analyze the degree of agreement between ASCO and ESMO frameworks. Methods: Anti-cancer agents from phase II or III randomized controlled trials (RCTs) cited for clinical efficacy evidence in drug approval by the Food and Drug Administration (FDA) between January 2011 and March 2018 were identified. Data required for ASCO-VF and ESMO-MCBS were extracted. Difference in how often long-term survival bonuses were awarded were calculated in all RCTs, as well as immune checkpoint inhibitor and non-immune checkpoint inhibitor RCTs individually. Cohen’s Kappa statistic was calculated to evaluate agreement between ASCO-VF and ESMO-MCBS. Results: 100 RCTs were analyzed. RCTs were awarded ASCO-VF version 2 (v2) “tail of the curve” bonuses more often than ESMO-MCBS version 1.1 (v1.1) “immunotherapy-triggered” long-term plateau adjustments (45% vs. 2.6%). Comparing to non-immune checkpoint inhibitor RCTs, immune checkpoint inhibitor RCTs were not more likely to receive ASCO-VF v2 bonuses/ESMO-MCBS v1.1 adjustments (p = 0.32/ p = 0.40). Long-term survival agreement between the two frameworks was poor (kappa: 0.01; p = 0.50). Conclusions: The ASCO-VF v2 and ESMO-MCBS v1.1 may require additional refinement in order to accurately capture the benefit of long-term survival or immune checkpoint inhibitor and non-immune checkpoint inhibitor agents may not preserve substantially different long-term survival populations.
AB0615 PREVALENCE OF DEPRESSION, ANXIETY, FATIGUE AND SLEEP DISTURBANCES IN PATIENTS OF RA, SLE AND GPA
Authors: Aman Sharma, Abhinav Shrivastava, Sandeep Grover, Saket Jha, Gsrsnk Naidu, Manish Rathi, Sanjay Jain
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The relative frequencies of co-morbidities like depression, anxiety, fatigue and sleep disturbance in RA, SLE and GPA are not fully elucidated. <h3>Objectives:</h3> To estimate and correlate the prevalence of depression, anxiety, fatigue and sleep disturbances in patients with RA, SLE and GPA by using time honored scales and PROMIS-HAQ<sup>1</sup>. <h3>Methods:</h3> This was a cross sectional study of 183 patients (RA – 57, SLE – 64, GPA – 62). Diagnosis and assessment of depression, insomnia, anxiety and fatigue was established by patient health questionnaire 9 (PHQ 9), Epworth sleepiness scale (ESS), generalized anxiety disorder assessment scale 7 (GAD 7) and fatigue severity scale (FSS) respectively. PROMIS-HAQ short form 8a was also used to diagnose depression, insomnia, anxiety and fatigue and its correlation with the above time honored scales was studied. <h3>Results:</h3> Mean age of RA, SLE and GPA patients was 45.5 ± 12, 31 ± 9.5 and 42.7 ± 13.5 years respectively. Mean disease duration was 5.7 ± 5.1, 3.3 ± 2.4 and 4.6 ± 4 years in RA, SLE and GPA respectively. Prevalence of depression, anxiety, fatigue, insomnia in RA, SLE and GPA as per standard scales and PROMIS HAQ is depicted in table 1. The corelation between the standard scales and PROMIS HAQ for depression [RA (r- .816, p&lt; .001), SLE (r- 0.625, p&lt; 0.001), GPA (r-0.772, p &lt;0.001)], anxiety [RA (r- .804, P&lt; .001), SLE (r- 0.709, p&lt;0.001), GPA (0.888, p&lt;0.001)], sleep disturbance [RA (r- .872, p&lt;0.001), SLE (r- 0.784, p&lt; 0.001), GPA (r-0.917, p &lt;0.001)] and fatigue [RA (r- .815, p&lt; .001), SLE (r- 0.798, p&lt; 0.001), GPA (r-0.805, p &lt;0.001)] was significant. <h3>Conclusion:</h3> Depression, anxiety, fatigue and sleep disturbance are common in RA, SLE and GPA. PROMIS HAQ has good correlation with time honoured scales for assesment of depression, anxiety, fatigue and sleep disturbance in these disorders. <h3>References</h3> [1] Cella D, Riley W, Stone a, et al. The Patient-Reported Outcomes Measurement information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol2010;63:1179–94. <h3>Disclosure of interests:</h3> None declared
Outcomes of metastatic colorectal cancer over fifteen years from an Indian tertiary care center: A retrospective analysis.
Authors: Vinod Sharma, Atul Sharma, Sushmita Pathy, Nootan Kumar Shukla, S V Suryanarayana Deo, Sanjay Thulkar, Sunil Kumar, Ranjit Sahoo
Journal: Journal of Clinical Oncology (2019)

e15050 Background: Management of metastatic colorectal cancer (CRC) has revolutionised over the past 2 decades and a number of drugs are part of active disease management including biologicals. Published large database on metastatic CRC outcome has been lacking from India. Methods: A retrospective data analysis of metastatic CRC from prospectively based database was performed from the year, 2001-2015. All patients who have received at least 1 cycle of chemotherapy were enrolled. Kaplan Meier analysis was done for overall survival (OS). Cox-regression model was done to determine prognostic factors of OS. Results: A total of 288 patients including upfront metastatic (n = 197, 68%) and relapsed (n = 91, 32%) with male to female ratio of 1.4:1 and median age of 46 years were studied. CEA was high in 78% with median level of 20 ng/ml. Most common site of primary tumor location was rectum (47%). Proportions of left side, right side and transverse colon was 75%, 20% and 4.2%. Mucinous and signet histologies were seen in 24% and 9.2% of patients. Most common sites of metastases being liver (43%), peritoneum (31%) and lung (18%). Oxaliplatin based therapy was used 71% of patients as 1 st line. Median chemotherapy cycles for both 1 st and 2 nd line regimen was 6. Biologicals were part of 1 st line regimen in only 12.5% of patients. Median OS of our cohort was 18.5 months. Predictors of poor OS were ECOG PS &gt; 1 (HR 2, CI: 1.3-3.3, p value = 0.003), high CEA ( &gt; 5ng/ml, HR 2.5, CI: 1.3-4.6, p value = 0.004), low albumin (&lt; 3.5 g/dl, HR 1.7, CI: 1.03-2.9, p value = 0.045), &lt; 2 lines of chemotherapy received (HR 2, CI: 1.3-3.3, p value = 0.001). Conclusions: Outcomes of metastatic CRC in our cohort with use of doublet chemotherapy (small proportion with biologicals) is comparable to published literature worldwide. We have higher proportion of younger population, rectum cancer, signet and mucinous histology and higher incidence of peritoneal involvement.
The financial impact of physician practice patterns: An analysis of as-needed filgrastim versus prophylactic pegfilgrastim in patients with prostate cancer receiving docetaxel.
Authors: Christine Barrett, Seon Jo Park, Kelly Gaertner, Shifeng Mao
Journal: Journal of Clinical Oncology (2019)

6506 Background: Docetaxel improves survival in metastatic prostate cancer. Patients receiving docetaxel are at an intermediate risk of febrile neutropenia (FN). Granulocyte-colony stimulating factor (G-CSF) reduces the incidence of neutropenia and infection. There is no consensus among physicians on G-CSF use with docetaxel in prostate cancer, and physician preference may significantly impact healthcare costs. The purpose of this study is to assess physician practice patterns by comparing efficacy and cost of as-needed filgrastim (ANF) to prophylactic pegfilgrastim (PPF) for neutropenia in patients with prostate cancer receiving docetaxel. Methods: This retrospective cohort study included patients with prostate cancer that received standard docetaxel and G-CSF, either ANF or PPF, from February 2016 to October 2018 at our institution. In the ANF arm, patients with an ANC less than 1000 cells/µL on day 8 of the cycle received filgrastim. In the PPF arm, patients received pegfilgrastim on day 2 for primary prophylaxis. Patient characteristics, chemotherapy dose intensity, delays, and reductions, and incidence of FN were collected. Results: Of the 65 patients included in this study, 32 received ANF and 33 received PPF. Patients in the ANF arm received an average of 6.0 cycles versus 4.8 cycles in the PPF arm (p = 0.013). The completion rate of planned cycles differed, with 93.8% completion in the ANF arm versus 66.7% in the PPF arm (p = 0.001). Average total drug exposure per patient was greater in the ANF arm than the PPF arm (437.5 mg/m 2 versus 343.4 mg/m 2 ; p = 0.007). In both groups, there was no significant difference in dose delays or reductions, or incidence of FN. However, there was a significant difference in cost, with an average of $740.26 per cycle per patient for filgrastim, versus $7327.72 per cycle per patient for pegfilgrastim, based on current average wholesale price. Conclusions: In our study, use of ANF was safe, and did not impact planned dose, intensity, or duration when compared to PPF. In addition, the administration of ANF was associated with significant cost savings. Analysis of G-CSF use in patients with prostate cancer receiving docetaxel at our institution has identified an opportunity for substantial healthcare cost savings.
Preclinical efficacy of copanlisib in cetuximab sensitive and resistant tumors of HNSCC.
Authors: Konrad Friedrich Klinghammer, Oliver Politz, Theresa Eder, Raik Otto, Jan D Raguse, Jens Hoffmann, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2019)

6031 Background: Copanlisib is a highly selective, pan-class I PI3K inhibitor with preferential activity against the p110α and p110δ isoforms that lead to downregulation of PI3K signaling. Copanlisib has been approved for the treatment of follicular lymphoma in the US. Here, we explored the anti-tumor activity of copanlisib in head and neck squamous cell carcinoma (HNSCC), where Pi3K signaling has been defined as alternate signaling in cetuximab resistant tumors. Further, TCGA data show up to 56% of HNSCC display either amplification or mutational changes in the Pi3K pathway making Pi3K an attractive target. Methods: Using a mouse-clinical trial set-up we profiled 20 patient derived HNSCC xenograft models for their sensitivity to cetuximab or copanlisib as single agent as well as in combination. Models were selected from our HNSCC PDX platform based on Pi3K mutational status, with 6 models harboring hot spot mutations, HPV positivity (n=3) and/or cetuximab resistance based on previous drug screenings (n=12). Treatment response was defined as tumor regression, stabilization or progression expressed as relative tumor volume (RTV) after 3 weeks of treatment: RTV&lt;0,7 responder, RTV&gt;1,2 progressor. Results: Copanlisib single agent treatment resulted in moderate activity with 5 responders (25%). In cetuximab resistant tumors (n=12) combined treatment led to an improved tumor response in 75% (n=9) whereas 41% (n=5) resulted in tumor control. Pi3KCA mutation was not predictive for treatment response to either cetuximab or copanlisib. No PTEN mutation was detected in the selected cohort. Increased Pi3K signaling activity evaluated through gene expression profiling and computed with GSEA pathway analyses was positively correlated with response. Conclusions: The anti-tumor responses observed in monotherapy or in combination treatment support further investigation for the potential of PI3K inhibition in HNSCC with high expression of Pi3K pathway signature as a potential predictive biomarker.
Randomized phase III study comparing carboplatin plus pemetrexed followed by pemetrexed versus docetaxel in elderly patients with advanced non-squamous non-small-cell lung cancer (JCOG1210/WJOG7813L).
Authors: Isamu Okamoto, Hiroshi Nokihara, Kiyotaka Yoh, Shunichi Sugawara, Hidehito Horinouchi, Koichi Azuma, Yasuto Yoneshima, Haruyasu Murakami, Haruko Daga, Yukio Hosomi, Shinji Atagi, Tomohiro Ozaki, Atsushi Horiike, Yuka Fujita, Hiroaki Okamoto, Masahiko Ando, Shogo Nomura, Nobuyuki Yamamoto, Yuichiro Ohe, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2019)

9031 Background: The aim of this phase III randomized trial is to determine the efficacy of pemetrexed and carboplatin followed by pemetrexed for elderly patients (pts) with advanced non-squamous non-small-cell lung cancer (NSCLC). Methods: Cytotoxic chemotherapy-naïve, ECOG-PS 0-1, aged 75 years or older, and advanced stage non-squamous NSCLC pts were randomized to receive either docetaxel 60 mg/m2 on day 1 every 3 weeks [DOC] or carboplatin AUC 5 mg/ml/min and pemetrexed 500 mg/m2 on day 1 every 3 weeks followed by maintenance therapy with pemetrexed 500 mg/m2 every 3 weeks after 4 cycles of carboplatin and pemetrexed [CBDCA/PEM] given until disease progression or unacceptable toxicities. The primary endpoint was OS. Non-inferiority of CBDCA/PEM arm was planned to be demonstrated if upper limit of 95% confidence interval (CI) for hazard ratio (HR) did not exceed 1.154. Results: Between August 2013 to February 2017, 433 pts with a median age of 78 years (range, 75 to 88) were randomly assigned to the DOC arm (n = 217) or the CBDCA/PEM arm (n = 216). Non-inferiority of CBDCA/PEM arm was confirmed in all enrolled patients (HR for OS, 0.850; 95% CI, 0.684 to 1.056, P &lt; 0.01). The median OS for DOC and CBDCA/PEM arms were 15.5 months and 18.7 months, respectively. In the CBDCA/PEM arm, PFS was significantly better (HR, 0.739; 95% CI, 0.609 to 0.89) and response rate was better (28.2% vs. 36.8%; P = 0.07), and incidence of neutropenia or febrile neutropenia of grade 3 or 4 was significantly lower. Grade 3 or 4 thrombocytopenia or anemia was more common in the CBDCA/PEM arm. Four treatment-related deaths (two in each treatment arm) occurred. QOL (FACT-LCS) was favorable for CBDCA/PEM arm throughout 18 weeks after enrollment. Conclusions: Pemetrexed/carboplatin followed by pemetrexed maintenance is a valid therapeutic option for the first-line treatment of elderly pts with advanced non-squamous NSCLC. Clinical trial information: 000011460.
CDX3379-04: Phase II evaluation of CDX-3379 in combination with cetuximab in patients with advanced head and neck squamous cell carcinoma (HNSCC).
Authors: Julie E. Bauman, Nabil F. Saba, Trisha Michel Wise-Draper, Douglas Adkins, Paul E. O'Brien, Margo Heath-Chiozzi, Philip Golden, Jennifer Drescher, Diego Alvarado, Richard Gedrich, Roger B. Cohen
Journal: Journal of Clinical Oncology (2019)

6025 Background: CDX-3379, an anti-ErbB3 monoclonal antibody with a half-life-extending YTE modification in its Fc region, binds a unique epitope that locks ErbB3 in an inactive form and inhibits ErbB3 signaling, the latter implicated in tumor growth/resistance to anticancer therapies. CDX-3379 enhances antitumor activity of targeted therapies in preclinical models. In a Phase 1 clinical study, CDX-3379 was well-tolerated alone and in combination with cetuximab. A durable complete response (CR) to CDX-3379 + cetuximab was observed (8.3 months) in a patient (pt) with cetuximab-refractory HNSCC (Falchook ASCO 2016). Methods: This open-label phase 2 study (NCT03254927) was designed to enroll up to 30 pts with advanced, HPV - , HNSCC, previously treated with cisplatin, anti-PD-1 antibodies, and cetuximab-resistant (progression within 6 months), according to a Simon’s 2-stage design (13 evaluable pts in Stage 1 with ≥1 objective response allows enrollment of 14 more pts in 2 nd stage). Pts receive CDX-3379 (initial dose 12 mg/kg IV every 21 days) + cetuximab (loading dose 400 mg/m 2 ; 250 mg/m 2 IV weekly) until disease progression/toxicity. Endpoints include objective response rate (primary), progression-free and overall survival, safety, pharmacokinetics, immunogenicity, and exploratory biomarkers. Results: Stage 1 accrual is complete with 14 evaluable pts treated. All pts were heavily pretreated; prior therapies included surgery (10/14) and chemotherapy (13/14). All pts had prior radiation, cetuximab and PD-1 targeted therapy. One confirmed ongoing CR (8.1+ months) was observed. 7/14 pts experienced stable disease (SD), including 4 with tumor shrinkage (8-27.5% reduction). Three pts continue treatment. Treatment-related adverse events were generally grade 1-2 and included diarrhea (53%), hypokalemia (20%), prolonged QT interval (13%) and rash (13%). Conclusions: CDX-3379 in combination with cetuximab is well tolerated with the primary toxicity of diarrhea. Signs of antitumor activity were observed in these cetuximab-resistant HNSCC pts, including an ongoing, durable CR. Complete stage 1 results will be presented. Clinical trial information: NCT03254927.
Methylated DNA markers (MDMs) in primary (pCRC) and metastatic colorectal cancers (mCRC).
Authors: Hao Xie, Douglas W. Mahoney, Molly M Peterson, Patrick H. Foote, Kelli Burger, Karen A Doering, William R. Taylor, Xiaoming Cao, Maria McGlinch, Calise K. Berger, Tsung-Teh Wu, Joleen Marie Hubbard, David A. Ahlquist, John B. Kisiel
Journal: Journal of Clinical Oncology (2019)

3599 Background: Existing tools for post-treatment CRC surveillance and monitoring are insensitive and expensive. MDMs are broadly informative for early detection of CRC but have not been extensively studied for disease monitoring. As a first step, we sought to assess the concordance of novel CRC-associated MDMs in pCRC and mCRC. Methods: A panel of 14 MDMs previously identified to be highly discriminant for pCRC was selected on the basis of high median fold-change of MDM levels relative to buffy coat (682 (IQR: 132-19347)). Surgically resected pCRC and paired mCRC were identified from institutional pathology databases. Quantitative methylation-specific PCR was used to assay MDMs. 30 paired samples per metastatic subtype were calculated to be sufficient. MDM levels were compared using two-sample and paired Wilcoxon rank sum tests. Results: 87 patients with paired pCRC and mCRC including 57 synchronous and 30 metachronous metastases were included. 41/87 (47%) had neoadjuvant and 59/87 (68%) had adjuvant chemotherapy. All synchronous metastases were to liver. Metachronous metastases were to liver in 19/30 (63%) and to lung in 11/30 (37%). The levels of 14 selected MDMs were remarkably similar between paired pCRC and mCRC (Table). Individual MDM levels and the average level of all MDMs combined were not significantly different ( p&gt; 0.0018 by Bonferroni correction). Conclusions: MDM levels are highly concordant in pCRC and mCRC. Thus, MDMs discovered from pCRC should be further studied for non-invasive surveillance after surgical resection and monitoring of treatment response in mCRC. [Table: see text]
Prognostic interaction of smoking history with circulating regulatory T cells in advanced non-small cell lung cancer.
Authors: Chao Liu, Yi Sun, Jinbo Yue, Jinming Yu
Journal: Journal of Clinical Oncology (2019)

e14030 Background: Smokers with non-small cell lung cancer (NSCLC) respond better to the inhibition of programmed cell death-1 (PD-1) with pembrolizumab than non-smokers do, which may be accounted for by the fact that smoking induces higher neoantigens and increased immunogenicity. Our investigation sought to highlight the prognostic interaction of smoking history with circulating regulatory T cells (Treg), CD3+, CD4+, and CD8+ T cells in advanced NSCLC. Methods: Using ﬂow cytometry, we assessed levels of circulating Treg cells, CD8+ T cells, CD4+ T cells, and CD3+ T cells in 106 eligible patients of 257 overall patients with advanced NSCLC. Results: Patients with high circulating Treg had shorter overall survival (OS) (12.5 vs. 27.5 months, P = 0.010) and progression-free survival (PFS) (7.1 vs. 16.9 months, P = 0.014) compared to patients with low Treg among non-smokers, but not among smokers (P = 0.211 for OS; P = 0.271 for PFS). Multivariate analysis showed Treg as an independent risk factor for outcomes of non-smoking patients [hazard ratio (HR): 2.71, P = 0.045 for OS; HR: 2.38, P = 0.047 for PFS], but not of smokers. Moreover, higher CD4+ T and lower CD8+ T cell counts, CD8/CD4 ratio, and CD8/Treg ratio were more abundant in non-smokers than smokers (all P &lt; 0.05). Conclusions: Smoking impacts the prognostic value of circulating Treg in advanced NSCLC. The distribution of circulating immune cells in non-smokers and smokers was different. Assessing the effect of cigarette smoking on circulating immune cells could help individualized immunotherapy for advanced NSCLC.
THU0696-HPR TRANSITION READINESS ASSESSMENT TOOLS (TRAT): A PRELIMINARY SINGLE-CENTRE PAEDIATRIC RHEUMATOLOGY TRANSITION PROGRAMME (PRTP) EXPERIENCE AND OUTCOMES IN SINGAPORE
Authors: Sook Fun Hoh, Xiaocong Gao, Yun Xin Book, Lena Das, Thaschawee Arkachaisri
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Majority of childhood onset rheumatic diseases often continue into adulthood. Care for these youth especially during their transition from child centred to adult oriented healthcare system is crucial and challenging. The Paediatric Rheumatology Transition Programme at KK Women's and Children Hospital (KKH) in Singapore was developed in 2016. In 2017, we have adopted the American College of Rheumatology Transition Readiness assessment tools (TRAT) with modification to assess the readiness of our paediatric rheumatology patient cohort. <h3>Objectives:</h3> To assess factors contributing to the outcomes of Paediatric Rheumatology Transition Programme at our institute using the Transition Readiness Assessment Tools (TRAT) <h3>Methods:</h3> The TRAT composed of 4 components – transition-importance, transition-confidence, medical knowledge/healthcare usage (MKHU-23 questions), transition-readiness assessment questionnaires (TRAQ, 5 domains – medicine management (MM), appointment management (AM), health issue tracking (HT), communications with providers (CP) and daily activity management (DAM)). Each component score was computed into 0-10 (scores &gt;7 defined acceptable responses). Nonparametric statistics were used to describe and analyse the data. <h3>Results:</h3> 106 patients (52.8% female) with SLE(42.5%) and JIA(50.0%)) with median age of 20.0 (18.8-20.6) years were recruited. Median duration of disease at 1st assessment was 7.0 years (IQR 5.5-8.8). 24 patients were transited successfully. Only 60% of our youths felt that transition preparation is important and had confidence to be prepared for/change to adult healthcare system (AHCS). Among the less confident group (scores &lt;7), MKHU, MM, AM and HT domains scored significantly less than those from confident youths (p&lt;0.001-0.021), but only transition importance MKHU scores were &lt;7. Disease duration at first TRAT assessment and diagnoses did not predict confidence level. With further targeted education and counselling (median 8.3 months (IQR 5.7-9.6)), confidence and MKHU was significantly improved (p=0.001). <h3>Conclusion:</h3> TRAT enables our PRTP team to learn and understand our local youths' perception and readiness of adult transition process. More than one-half of them did not aware of the importance of the transition process and had less confidence to do so. With further targeted counselling and preparation, all improved their perception and MKHU significantly. TRAT was able to guide individualize counselling to our cohort youths who are ready to be transited. <h3>Acknowledgement:</h3> American College of Rheumatology <b>Disclosure of Interests:</b> Sook Fun Hoh: None declared, Xiaocong Gao: None declared, Yun Xin Book: None declared, Lena Das: None declared, Thaschawee Arkachaisri Speakers bureau: Abbvie Pte, Ltd