tbuckley/cabot-search huggingface dataset:
A method to assess <i>KRAS/BRAF</i> genotype in patients with metastatic colorectal cancer (mCRC) elligible for anti-EGFR therapies.
Authors: A. Lamy, E. Labourier, O. Prigneau, F. Di Fiore, R. Sesboüá, J. Sabourin
Journal: Journal of Clinical Oncology (2011)

383 Background: KRAS/BRAF mutation screening is a new diagnostic tool since activating mutations, especially for KRAS, are strong negative predictive factors for anti-EGFR monoclonal antibody therapies. Therefore, standardized, reliable, and rapid mutation detection methods are needed. The goal of the present study is to evaluate the concordance between a clinically validated laboratory-developed KRAS/BRAF SNaPshot test and a novel research use assay, the Signature KRAS/BRAF Mutations kit (Asuragen Inc.), in representative clinical specimens. Methods: Genomic DNA from FFPE mCRC specimens previously tested with the SNaPshot assay were analyzed using the Signature KRAS/BRAF mutations assay. The Signature assay consists of multiplex PCR followed by multiplex hybridization to fluorescent beads coupled to capture probes and detection on the Luminex analyzer. The qualitative assay detects 12 mutations in KRAS codons 12/13 and BRAF V600E based on the median fluorescence intensity (MFI) generated by each bead above (positive) or below (negative) a fixed cut off. Results: To date, KRAS/BRAF mutational status was successfully assessed with the signature assay in 248 samples. After initial testing, signature and SNaPshot assays were in qualitative agreement for 232 samples (93.5%): 166 positive for KRAS, 46 positive for BRAF, and 20 double negative. 16 samples (6%) presented discrepant results: (i) 11 false negative samples with fluorescence signals for the expected mutations above the average assay background signal but below the 450 MFI positive cut off preselected for this study (330-431 MFI), (ii) 3 samples positive for both KRAS and BRAF and (iii) 2 false positive samples. 7 discrepant samples have been retested to date resulting in an overall agreement of 99.6% (239/240). However, different KRAS mutations were identified by the SNaPshot and signature assays in 3 positive samples. Conclusions: The signature KRAS/BRAF mutations assay is an attractive method, easy to use, less time consuming than the SNaPshot assay, and potentially adaptable to routine clinical testing. Further analysis will establish and validate cut offs to be used in routine diagnostic procedures. No significant financial relationships to disclose.
Exploratory biomarker analyses from OAM4558g: A placebo-controlled phase II study of erlotinib with or without MetMAb in patients with advanced non-small cell lung cancer (NSCLC).
Authors: W. Yu, A. Pandita, E. Penuel, R. Raja, J. Zha, S. Mohan, R. D. Patel, R. Desai, L. Fu, A. Do, J. Mango, V. Parab, M. Lipkind, J. Huang, M. Lazarov, V. Ramakrishnan, L. C. Amler, A. C. Peterson, P. H. Patel, R. L. Yauch
Journal: Journal of Clinical Oncology (2011)

7529 Background: MetMAb, a monovalent anti-cMet receptor antibody, inhibits HGF-mediated activation of c-Met. The Phase II study testing MetMAb in combination with erlotinib in patients with advanced NSCLC (n=128) demonstrated an OS benefit in Met Diagnostic (Dx)+ patients (n=65, defined as ≥50% of tumor cells staining 2+ or 3+ intensity for c-Met by IHC; HR=0.37, p=0.002). Methods: Exploratory tumor biomarkers related to c-Met and/or EGFR signaling were measured by FISH, qRT-PCR or various mutation detection techniques from archival tumor tissue specimens. Plasma HGF levels were measured by ELISA. Analyses with outcome were carried out independent of Met Dx status. Results: Baseline characteristics of patients with evaluable tumor or plasma specimens were generally comparable. MET gene copy number was evaluated in 96 specimens with a median mean copy number of 3.44 copies/cell (range 1.6–25.0) and true gene amplification was detected in 8%. Analysis of different copy number cutoffs revealed a non-significant trend toward improved OS when MET FISH-positivity was defined as ≥5 copies/cell (HR=0.47, p=0.19), but not at lower thresholds ≥4 copies (HR=0.89, p=0.82). An OS HR of 1.37 (95% CI: 0.43-4.36) was observed in 23 patients with both MET and EGFR FISH copy number gains (high polysomy or amplification). EGFR mutations were detected in 12% (13/112) of evaluable specimens; mutations were detected in 6 of 7 patients with objective responses. KRAS mutations were detected in 23% (26/112) of evaluable specimens and status did not affect OS for patients on MetMAb. High expression levels (≥median) of MET, HGF, EGFR, AREG or EREG mRNA did not independently predict an OS benefit. However, in the patient population for whom qRT-PCR data was available (n=67), the OS benefit in Met Dx+ patients was not as apparent (HR=0.69, p=0.48). A trend in improved OS on MetMAb was additionally observed in patients with low (<median) baseline plasma HGF levels (HR=0.46, p=0.11). Conclusions: The data continues to support c-Met IHC as a sensitive and independent predictor of OS benefit from MetMAb. Continued investigation of biomarkers is warranted in future clinical studies.
Beyond claims data: Assessing the problem of access to radiation therapy for low-income women with breast cancer
Authors: W. R. Carpenter, B. J. Weiner, L. C. Richardson, J. A. Lee, J. M. Peppercorn, M. A. Lewis, J. T. Whitmire, S. P. Walden, L. O. Hinson
Journal: Journal of Clinical Oncology (2008)

6579 Background: Despite long-standing consensus guidelines, the literature reports that one third of low-income women with early-stage breast cancer who undergo breast conserving surgery (BCS) do not receive radiation therapy (RT). Methods: The University of North Carolina Rapid Case Ascertainment (RCA) program and registrars at 40 North Carolina hospitals identified women recently diagnosed with early- stage breast cancer. Medicaid enrollment records and claims were reviewed for six months prior to and six months following surgery. For women with claims for BCS but not RT, RCA obtained pathology reports and operative notes to verify eligibility. Eligible women with claims for BCS but not RT were contacted for a qualitative study examining reasons for non-receipt of RT. Results: During the first six months of the study, 638 women with Stage I/II breast cancer were identified. 69 (10.8%) had Medicaid claims in the ± six month study window. Claims indicated that 25 of 44 (57%) women received RT after BCS. For the 19 (43%) with no RT claims, 5 had medical records indicating appropriate RT, non- carcinoma, or more extensive surgery (mastectomy) than claims indicated. Upon contacting the remaining 14 patients, 7 reported receipt of RT, 1 had died, 1 failed to attend the scheduled interview. Even after 2 months of effort, 5 could not be reached by phone. A review of claims, medical records, and contact with patients indicate that 86% (37/43) of women received appropriate care, 1 had inappropriate non-receipt of RT (2%), and 5 (12%) remain unconfirmed. At least 4 of 19 (21%) women without RT claims received RT at different facilities from the facility where the surgery was performed. Conclusion: This ongoing study suggests receipt of RT following BCS for Medicaid-insured women is more common than reported in the literature. The absence of RT receipt in Medicaid claims or single-facility records does not necessarily indicate inappropriate breast cancer care. Obtaining a comprehensive and accurate picture of care for this population is exceptionally challenging, and necessitates the use of multiple information sources, including the patient. No significant financial relationships to disclose.
Clinical and health care setting of patients admitted at Pain Control Center Hospice of Solofra: A feasibility model of end-of-life care in the Avellino province of Italy.
Authors: Geppino Genua, Carmela Fasano, Luisa M. Rizzo, A. M. Strollo, Elena De Vinco, Vincenzo Landolfi, Elena Altieri, Mario Nicola Vittorio Ferrante, Sergio Canzanella, Giuseppe Servillo, Lucia Genua, Maddalena Zampi, Gaetano D'Onofrio
Journal: Journal of Clinical Oncology (2016)

59 Background: The Pain Control Center Hospice of Solofra (Italy) is managed with a mixed public / private, the first experience in the Campania region.We have evaluated the treatment procedures and the clinical outcome to make a comparison by between 123 evaluable patients in palliative care in 2015 and 232 evaluable patients in the biennium 2012-2014. Methods: The following characteristics: patient gender, mean hospitalization time, differentiation between cancer and non cancer patients, medical weapon use, venous access type, enteral and parenteral feeding, pain killer use,Karnofsky scale. Results: the average age is nearly overlapping being 70.5 yr vs 70.69 yr; average length of stay in hospice 24.33 days vs. 27.52 days; 79.67% had cancer vs 73.70%, while the non-cancer 20.32% vs 26.30%; 55.26% died in hospice vs 71.98%, while 44.7% were discharged home vs 24.56%; the performance status according to Karnofsky scale before admission to hospice 23.1% had index rating (%)- 50, 10.56 -40, 52.03%-30, 35.7%-20, 23.1%-10. 8.9% had ostomy vs 13.79%; 4.4% were carriers of PEG vs 6.3%; the central venous access already implanted at admission in 32.52% vs 26.72%; enteral feeding was administered in 23.7% vs 13.79% and parenteral feeding in 52.84% vs 46.98%; analgesic therapy with more opiates was already present on admission in 48.78% vs 40.94% with prevalence of trans TD formulations. Analgesic therapy was administered during the hospitalization in 66.66% vs 81.89%. 14.28% of cancer patients in 2015 have received morphine treatment vs 15.3%, 22.11% oxycodone / naloxone vs 19%, 58.16% trans-dermal fentanyl vs. 34%, 14.7% have supplements onset fentanyl, 2.4% with tapentadol vs na, 15.30% tramadol vs 9%, 4.2% codeine vs 15.3%. Conclusions: This report is a feasibility model of end of life-care in the Avellino province submitted to the public administrative control with the private organization supporting House Hospital Onlus. The present study shows gradual improvement of the knowledge of palliative care by the family doctors and the population of a territory with peculiar topography and induces public health authority to improve the care offered.
Comparative effectiveness and resource utilization of <i>nab</i>-paclitaxel plus gemcitabine (<i>nab</i>-P+G) versus gemcitabine monotherapy (G) in first-line treatment of advanced pancreatic adenocarcinoma (PDAC) in a U.S. community oncology setting.
Authors: Fadi S. Braiteh, Manish Patel, Monika Parisi, Quanhong Ni, Si yeon Park, Claudio Faria
Journal: Journal of Clinical Oncology (2016)

429 Background: Based on a randomized clinical trial (RCT), nab-P+G had superior overall survival (OS) compared to G for the treatment of advanced PDAC, but limited data is available comparing the effectiveness of these treatment options in a real-world setting. The objective of this study is to compare treatment patterns of patients receiving nab-P+G versus G for first-line treatment of PDAC. Methods: A retrospective cohort study was performed using fully de-identified data from a nationally representative electronic medical record platform of 1,300 community oncology physicians. Patients diagnosed with advanced PDAC between September 2013 and October 2014 who received first-line therapy with either nab-P+G or Gm were included in the analysis. We calculated the median time to treatment discontinuation (TTD) and database persistence (DP), a proxy for OS, using the Kaplan Meier method, and assessed supportive care usage with Poisson regression. Results: Out of 851 patients, 168 met eligibility criteria for the analysis (nab-P+G, n=122; G, n=46). Patients in the nab-P+G arm were younger (mean age 67.0 v 72.0; p &lt;0.01) and mostly males (60% v 44%). Other baseline characteristics were comparable. Patients treated with nab-P+G had a statistically significant longer median TTD (3.4 v 2.2 mos; p &lt;0.01) and median DP (8.6 v 5.3 mos; p=0.03). Patients receiving nab-P+G had fewer AEs-related to discontinuation (18% v 26%); but they utilized more doses of granulocyte-colony stimulating factor (2.02 v 0.73 doses, p&lt;0.01), erythropoietin-stimulating agents (0.90 v 0.54, p&lt;0.01) and steroids (7.89 v 0.58 doses, p&lt;0.01) per 100 days compared to patients receiving G. Conclusions: Similar to the RCT comparing nab-P+G with G,patients receiving nab-P+G experienced significantly longer TTD and DP in this real-world analysis compared to patients receiving G. Additionally, patients receiving nab-P+G had fewer AEs leading to discontinuation compared to patients receiving G. More supportive care may have been used in the nab-P+G group due to longer treatment duration.
A phase I trial of cixutumumab (C) (IMC-A12) and sorafenib (S) for treatment of advanced hepatocellular carcinoma (HCC).
Authors: Anthony B. El-Khoueiry, Robert O'Donnell, Philip C Mack, Suzette Blanchard, Nathan Bahary, Yixing Jiang, Yun Yen, John Joseph Wright, Helen Chen, Heinz-Josef Lenz, David R. Gandara
Journal: Journal of Clinical Oncology (2014)

293 Background: The insulin growth factor (IGF) pathway is activated in hepatocarcinogenesis. C is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). In vivo HCC models show activated IGF signaling and antitumor effects due to C. Given the cross-talk between the IGF and VEGF pathways, the combination of C and S was chosen for study. Methods: This study evaluated the safety of C (2, 4 or 6 mg/kg) IV weekly with standard doses of S (400 mg po bid) in patients (pts) with HCC without standard curative options. Eligibility criteria included: no prior systemic therapy, Child-Pugh score of A or B7, ECOG 0 or 1, platelets &gt; 75,000/mm3, and albumin &gt; 2.8 g/dl. The study used a standard 3+3 design. One cycle was 28 days. Results: A total of 21 pts (17 males and 4 females) were enrolled; mean age was 63 years (43-85); 10 Asian, 4 Hispanic, 5 White, 1 Black, and 1 Native American. There were 3 dose limiting toxicities (DLTs); grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade 5 peritonitis (table). The maximum tolerated dose (MTD) was C 4 mg/Kg and S 400 mg BID. Eighteen of 21 (86%) pts had ≥ grade 3 toxicities attributable to treatment. Grade 3 adverse events that occurred in ≥ 2 pts were: diarrhea (4; 19%), hypertension (4; 19%), thrombocytopenia (3; 14%), palmar-plantar erythrodysesthesia (2; 10%), hyperglycemia (2; 10%), and fatigue (2; 10%). There was one grade 4 colonic perforation and one grade 5 peritoneal infection in the same pt. The median number of cycles completed was 4 (0-19 cycles). Sixteen of the 21 pts completed 2 cycles and were evaluated for response. Thirteen of the sixteen (81%) (95% CI: 54%-96%) achieved stable disease. The median event-free survival was 3.8 months (95%CI: 1.9, 11.3). The median OS was 13.1 months (95% CI: 7.6, undefined). Conclusions: The majority of adverse events in pts treated with the combination of C and S were typical of sorafenib toxicity. There was preliminary evidence of efficacy as seen in the median OS. Analysis of biomarker correlative data is on-going. Clinical trial information: NCT01008566. [Table: see text]
Characterization of systemic therapy utilization in 274 patients with de novo metastatic breast cancer and effect of novel chemotherapeutic agents on survival.
Authors: R. A. Nelson, J. E. Mortimer, M. E. Dehaven, S. Onami, L. Bernstein, S. K. Pal
Journal: Journal of Clinical Oncology (2011)

e11589 Background: Existing reports suggest a temporal trend towards improved survival in patients with de novo metastatic breast cancer (dnMBC) over the past two decades [Andre F et al J Clin Oncol 22:3302, 2004]. However, these reports do not specifically account for utilization of novel chemotherapeutic agents—at present, its contribution to improved survival remains unclear. Methods: A chart review of 305 patients diagnosed with dnMBC between Jan 1, 1985 and Dec 31, 2004 was conducted, with a detailed account of systemic therapies rendered. Chemotherapy use was stratified into two groups: (1) category A (cA), including drugs approved or principally in use prior to Jan 1, 1995 (5-FU, anthracyclines, cyclophosphamide, etoposide, ifosfamide, methotrexate and platinum), or category B (cB), including drugs approved or principally in use after Jan 1, 1995 (capecitabine, docetaxel, gemcitabine, ixabepilone, liposomal doxorubicin, paclitaxel and vinorelbine). These variables were incorporated in a multivariate model that included clinicopathologic features (age, hormone receptor status, HER2 status, etc.), endocrine therapy use, and bisphosphonate use to identify predictors of survival. Results: 31 patients were excluded due to characterization of stage IV disease on the basis of supraclavicular adenopathy alone. In the remaining 274 patients, median survival was improved in patients diagnosed with dnMBC between Jan 1, 1995-Dec 31, 2004 as compared to Jan 1, 1985-Dec 31, 1994, although this was not statistically significant (3.0 v 2.5 yrs, P=0.17). On multivariate analysis, no difference in survival was noted between patients who received chemotherapeutic agents in cA as compared to cB (P=0.81). However, use of selective estrogen receptor modulators, aromatase inhibitors and fulvestrant independently predicted for improved survival (P<0.05 for each). Conclusions: Mirroring prior reports, there was a temporal improvement in survival amongst patients with dnMBC, albeit non-statistically significant. The introduction of novel chemotherapeutic agents does not appear to account for this trend, however.
A phase II study of concurrent pemetrexed and radiation for poor-risk stage III non-small cell lung cancer (NSCLC): Hoosier Oncology Group LUN08-129.
Authors: J. L. Feliciano, N. H. Hanna, A. Fakiris, M. Yu, W. M. Dugan, J. McClean, J. A. Bufill, S. Bhatia, J. D. Patel
Journal: Journal of Clinical Oncology (2011)

e17529 Background: One third of patients with NSCLC present with locally advanced disease and the standard therapeutic approach is concurrent chemoradiotherapy. The optimal regimen for patients with pre-existing “poor risk” prognostic factors is not defined since they are often excluded from clinical trials despite comprising 30-40% of newly diagnosed stage III NSCLC. An effective tolerable regimen is needed. Methods: We planned to prospectively evaluate the efficacy and tolerability of concurrent pemetrexed (500mg/m2 on day 1 q 21 days for 3 cycles) and radiation (2.0 Gy, 5 days/week for 6 weeks) in 44 poor-risk patients with locally advanced non-squamous NSCLC. Eligibility included at least one of the following: ECOG PS=2, albumin < 0.85 institutional lower limit, weight loss >10% in the preceding 6 months, and FEV1 between 1-1.5 L. Normal organ function and blood counts were required. The 1° endpoint of the study was PFS. Secondary endpoints were toxicity and OS. Treatment was discontinued for progressive disease, unacceptable toxicity, patient request, treatment delay >21 days. Stopping rules included unacceptably high grade 4 toxicity rate (2/10, 4/20, 7/30, or 10/44 patients). Results: 8 patients were enrolled between 1/09 and 12/10. All 8 patients completed radiation treatment. 6 patients received 3 cycles of pemetrexed and 2 patients received 2 cycles. Most Frequent grade 1/2 toxicities: fatigue (7/8); anorexia (6/8); cough (6/8). Most frequent grade 3/4 toxicities; fatigue (4/8); anorexia (3/8); and neutropenia (3/8). The study closed prematurely due to withdrawal of pharmaceutical funding. Therefore, there was not sufficient power to calculate Kaplan-Meier estimates. However, of note 3 patients experienced a confirmed best response of PR per RECIST criteria. Two additional patients had unconfirmed PRs. Conclusions: It is difficult to complete a trial for “poor risk” patients despite a cooperative group setting. While this regimen showed promising efficacy and tolerable toxicity, further research is needed.
A phase II study of panitumumab plus irinotecan for metastatic colorectal cancer with wild KRAS, resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese (OGSG1001).
Authors: Koichi Taira, Motoki Yoshida, Naotoshi Sugimoto, Takayuki Kii, Shin Kuwakado, Mutsumi Fukunaga, Hiroko Hasegawa, Takeshi Kato, Yasuhiro Miyake, Taishi Hata, Yukihiko Tokunaga, Koji Takeda, Haruko Daga, Tetsuhiro Yoshinami, Toshio Shimokawa, Daisuke Sakai, Yukinori Kurokawa, Taroh Satoh, Toshimasa Tsujinaka, Hiroshi Furukawa
Journal: Journal of Clinical Oncology (2014)

607 Background: Anti-epidermal growth factor receptor (EGFR) antibody therapy showed to be effective in treatment for metastatic colorectal cancer (mCRC) with wild KRAS. Especially, combination chemotherapy with anti-EGFR antibody plus irinotecan is expected more effective than anti-EGFR antibody alone, resistant to irinotecan. We conducted a phase II trial of panitumumab plus irinotecan for mCRC with wild KRAS resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese. Methods: Subjects were mCRC patients with wild KRAS, who showed resistance to fluoropyrimidine, oxaliplatin, and irinotecan and had measurable disease, ECOG PS 0-2. Panitumumab (6 mg/kg) plus irinotecan (same dose as prior irinotecan) was administered every two weeks. This treatment was provided until progression. The primary endpoint was response rate (RR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), response duration, and adverse event (AE). Results: A total of 31 subjects were enrolled between July 2010 and July 2012. Median age was 64 years old (range 42-74). Nineteen patients had liver metastasis, 11 had lung metastasis, and 3 had lymph node metastasis. An independent review committee evaluated for efficacy in eligible 31 subjects in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The RR of primary endpoint was 29.0% (95% confidence interval (CI), 14.2-48.0 %). DCR was 74.2% (95%CI, 55.4-88.1%) and median PFS was 5.6 months.(95%CI: 3.4-8.7) In 31 subjects for safety evaluation, the incidence of any Grade 3 or greater adverse events was 58.1%. Major adverse events of grade 3 were diarrhea (19.4%), rash acneiform (12.9%), fatigue (9.7%), anorexia (9.7%). A sudden death and an infusion related reaction were occurred. Conclusions: Combination chemotherapy with panitumumab plus irinotecan was demonstarated to be safe and more effective than Japanese single arm phase II of panitumumab alone for mCRC, resistant to fluoropyrimidine, oxaliplatin and irinotecan. This result in Japanese is equal to other reports of panitumumab plus irinotecan. Clinical trial information: UMIN000003819.