tbuckley/cabot-search huggingface dataset:
Impact of first-line bevacizumab (BV) on the clinical outcomes of patients with metastatic colorectal cancer (mCRC) treated with second-line FOLFIRI plus BV.
Authors: Kei Muro, Takeharu Yamanaka, Mitsukuni Suenaga, Tomohiro Nishina, Hisateru Yasui, Takashi Ura, Tadamichi Denda, Junichi Ikeda, Taito Esaki, Hogara Nishisaki, Yoshinao Takano, Ken Kondo, Koji Takeda, Yasuo Takahashi, Kazuya Endo, Yasuyuki Sugiyama
Journal: Journal of Clinical Oncology (2014)

e14565 Background: In a phase II study (CR0802; UMIN000001817) of second-line FOLFIRI plus BV for mCRC, quarter of the enrolled patients did not receive BV in their first-line treatment. We analyzed the impact of prior BV use on the outcomes of FOLFIRI plus BV. Methods: Patients with FOLFOX-pretreated mCRC received up to 24 cycles of FOLFIRI plus BV. The efficacy of the treatment was compared between patients who had previously received BV (i.e., FOLFOX plus BV) and those who had not. Results: Patient characteristics were well-balanced between patients with (N =69) and without (N =20) prior BV use in the first-line treatment. Progression-free survival (PFS) and overall survival (OS) from the start of second-line treatment significantly differed between the two groups in favor of those without prior BV use (Table). Response rate (RR) for patients without prior BV use was higher than that for those with prior BV use. There was no substantial difference in median relative dose intensity of FOLFIRI plus BV as well as post chemotherapy between the two groups. Multivariate analyses also confirmed these results. Conclusions: Our analysis suggests that a prior BV use in the first-line treatment may reduce the efficacy of second-line FOLFIRI plus BV for colorectal cancer. Clinical trial information: UMIN000001817. Pretreated with BV (N=69) Pretreated without BV (N=20) P Hazard ratio (95%CI) 2nd line PFS, median 4.5 mo 8.8 mo 0.0062* 2.10 (1.22 - 3.62) 2nd line OS, median 12.3 mo 25.9 mo < 0.0001* 3.65 (1.90 - 7.01) 2nd line RR 7.2 % 20.0 % 0.1102** - * Logrank test. ** Chi-squared test.
Two-year follow-up of a phase II study on catumaxomab as part of a multimodal approach in primarily resectable gastric cancer.
Authors: Carsten Bokemeyer, Karsten Ridwelski, Djordje Atanackovic, Dirk Arnold, Ewald Woell, Markus W. Büchler, Colin Krueger, Christoph Schuhmacher
Journal: Journal of Clinical Oncology (2012)

4095^ Background: Perioperative chemotherapy (CT) has demonstrated as survival benefit in locally advanced gastric cancer (GC) in randomized trials. However, the overall cure rate is 30-40% and a significant number of patients are not able to receive the postoperative part of their CT regimen. In Europe, the trifunctional antibody catumaxomab is approved for the treatment of malignant ascites based on a pivotal trial which also included GC patients. A new multimodal approach combining neoadjuvant CT, followed by gastrectomy and intraperitoneal (i.p.) immunotherapy with catumaxomab was assessed in a single-arm multicenter phase II study. We here report 2-year follow-up data. Methods: GC pts (T2/T3/T4, N+/–, M0) received 3 cycles of neoadjuvant fluoropyrimidin/platinum-based CT followed by ’en-bloc’ R0-gastrectomy. Catumaxomab was administered i.p. as intraoperative bolus (10 µg) followed by 4 consecutive 3-hour infusions of 10-150 µg. Primary safety endpoint was the rate of predefined postoperative complications observed during 30 days after surgery. Key efficacy endpoints included disease-free (DFS) and overall survival (OS). Results: The original study data presented at the WCGC in 2011 (Schuhmacher et al.,Ann Oncol (2011) 22(suppl. 5)) showed that the primary endpoint was met and the described application regimen is safe. At time of surgery, 27.8% of patients were stage I, 27,8% of patients were stage II, 22,3% of patients were stage III and 14,8% of patients were stage IV as assessed according to pTNM measures. At 24 months 39/54 (safety analysis set) patients were still alife,14/54 were dead, (one patient lost to follow-up), 24/37 had no progression, only 13/37 patients relapsed (for 2 patients disease status was not recorded). At the 2 year cut off DFS was 56.4% (95% CI: 41–69%), OS was 75% (95% CI: 60–85%). Conclusions: Catumaxomab as part of a multimodal therapy in primarily resectable GC is a feasible option. The 2-year follow up efficacy results show promising data for DFS and OS in a cohort of locally advanced gastric cancer pts.
Proteomics of Atrial Fibrillation
Authors: Matthew C. Hyman, Rajat Deo
Journal: JAMA Cardiology (2017)

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Efficacy and safety of regorafenib compared to TAS-102 for metastatic colorectal cancer: A systematic review and network meta-analysis.
Authors: Ana Beatriz Kinupe Abrahao, Yoo-Joung Ko, Kelvin K. Chan, Scott R. Berry
Journal: Journal of Clinical Oncology (2017)

735 Background: Recent studies have shown regorafenib and TAS-102 (TAS) to be superior to placebo (P) in refractory metastatic colorectal cancer (mCRC). However, no studies have directly compared both drugs. Giving the lack of therapeutic options for these patients,, a systematic review to compare the efficacy and safety of regorafenib compared with TAS was performed, using indirect comparison methods. Methods: A systematic review using PubMed, Medline, Embase, Scopus and Cochrane database to identify published and unpublished studies up to November 2015 for randomized controlled trials (RCTs) for patients with metastatic colorectal cancer, involving regorafenib or TAS was performed. Data including overall survival (OS), progression-free survival (PFS) and toxicity were extracted. Pairwise direct meta-analyses (regorafenib versus placebo and TAS versus placebo) and indirect comparison (regorafenib versus TAS) using network meta-analyses methods (R package “netmeta”) to preserve randomization were performed using random effects. Results: 914 citations were initially identified among which 3 RCTs fulfilled eligibility criteria (CORRECT, CONCUR and RECOURSE trials) involving 1.764 patients (regorafenib: 641, TAS: 534, Placebo: 589). Subgroups of patients (1.659) who had not received prior regorafenib or TAS-102 were used to performed meta-analyses for efficacy. In indirect comparison, there were no statically differences observed between regorafenib and TAS-102 in overall survival (HR 0.96 95% CI 0.56-1.55 p = 0.082) and progression-free survival (HR HR 0.85 95% CI 0.40-1.80 p = 0.0182). In addition, there were no differences in objective response rate and disease control between both drugs. However, regorafenib has statistically more all grade toxicity (risk difference (RD) 0.31 CI 0.25-0.38 p = 0.001) and toxicity grade 3-5 (RD 0.22 CI 0.13-0.31 p &lt; 0.001) compared to TAS. Conclusions: In this indirect comparison, regorafenib and TAS appeared to have similar efficacy. However, regorafenib has more toxicity compared to TAS. Post-approval real world data focusing on the comparative toxicity of regorafenib and TAS is warranted.
Predictive value of phase II clinical trials in pancreatic cancer: Rethinking the road to progress.
Authors: Daniel M. Halperin, J. Jack Lee, James C. Yao
Journal: Journal of Clinical Oncology (2013)

4036 Background: Few new therapies for pancreatic adenocarcinoma (PC) have been approved by the Food and Drug Administration (FDA) or recommended by the National Comprehensive Cancer Network (NCCN), reflecting frequent failures in phase III trials. We hypothesize that the high failure rate in large trials is due to a low predictive value for “positive” phase II studies. Methods: Given a median time from initiation of clinical trials to FDA approval of 6.3 years, we conducted a systematic search of the clinicaltrials.gov database for phase II interventional trials of antineoplastic therapy in PC initiated from 1999-2004. We reviewed drug labels and NCCN guidelines for FDA approval and guideline recommendations. Results: We identified 70 phase II trials that met our inclusion criteria. Forty-five evaluated compounds without preexisting FDA approval, 23 evaluated drugs approved in other diseases, and 2 evaluated cellular therapies. With a median follow-up of 12.5 years, none of these drugs gained FDA approval in PC. Four trials, all combining chemotherapy with radiation, eventually resulted in NCCN recommendations. Forty-two of the trials have been published. Of 16 studies providing pre-specified type I error rates, these rates were ≥0.1 in 8 studies, 0.05 in 6 studies and &lt;0.025 in 2 studies. Of 21 studies specifying type II error rates, 7 used &gt;0.1, 10 used 0.1, and 4 used &lt;0.1. Published studies reported a median enrollment of 47 subjects. Fourteen trials reported utilizing a randomized design. Conclusions: The low rate of phase II trials resulting in eventual regulatory approval of therapies for PC reflects the challenge of conquering a tough disease as well as deficiencies in the statistical designs. New strategies are necessary to quantify and improve odds of success in drug development. Statistical parameters of individual or coupled phase II trials should be tailored to achieve the desired predictive value prior to initiating pivotal phase III studies. Positive predictive value of a phase II study assuming a 1%, 2%, or 5% prior probability of success and 10% type II error rate. [Table: see text]
Preclinical activity of lenalidomide in metastatic colorectal cancer.
Authors: Valeria Leuci, Federica Maione, Maja Todorovic, Enrico Giraudo, Loretta Gammaitoni, Giorgia Migliardi, Massimo Aglietta, Francesco Leone, Livio Trusolino, Andrea Bertotti, Dario Sangiolo
Journal: Journal of Clinical Oncology (2013)

e14654 Background: Metastatic colorectal cancer (mCRC) is currently considered incurable. Recent evidences support the importance of micro-environment and angiogenesis on survival and propagation of mCRC. Lenalidomide is a derivative of thalidomide, effective in several hematologic disorders, whose activity includes modulation on tumor microenvironment and inhibition of angiogenesis. We investigated the preclinical activity of lenalidomide against mCRC in vitro and in vivo. Methods: CRC cell lines and primary mCRC cells were treated with scalar concentrations of lenalidomide (10 to 150 µM). Two cohorts of NOD/SCID mice (n=8) implanted with mCRC xenografts derived from two different patients were treated orally for 21 consecutive days with Lenalidomide (50 mg/Kg/die). Results: In vivo a significant reduction of tumor growth was observed in one cohort compared to untreated controls (n=8), 247±118 mm 3 vs. 567±216 mm 3 (P=0.02), while no significant differences occurred in the second cohort. Pathology review on tumor samples removed from the mice revealed a trend toward the restoration of normal colon tissue morphology and architecture in lenalidomide treated samples compared to untreated controls. Quantitative evaluation of tumor angiogenesis on the responsive cohort, by immunohistochemistry for factor VIII, revealed a tumor-vessel reduction of 49% with lenalidomide compared to controls. Moreover, necrotic-hypoxic areas were reduced by 6 fold in lenalidomide treated xenografts compared to untreated controls (P&lt;0.001). Treatment in vitro did not result in any direct antitumor effect. The average rate of cell death in treated samples was 15.5±2.1%, 15.3±6.7%, and 11.5±3.4% at lenalidomide doses of 10, 40 and 150 µM respectively, compared to 14.6±2.6% of untreated controls. Conclusions: Our data indicate a potential activity of lenalidomide against mCRC. The beneficial effect was limited in-vivo, supporting the hypothesis that the main activity of lenalidomide is exerted through modulation of tumor microenvironment and angiogenesis rather than a direct antitumor effect. Our findings may be of clinical relevance and support further investigations to explore the benefit of lenalidomide in the challenging setting of mCRC.
Development of a decision aid for young canadians diagnosed with breast cancer who are at risk of infertility following cancer treatment.
Authors: Brittany Speller, Marcia Facey, Amanda Sissons, Corinne Daly, Erin Diane Kennedy, Kelly A. Metcalfe, Nancy N. Baxter
Journal: Journal of Clinical Oncology (2017)

108 Background: Young breast cancer patients are at risk of temporary or permanent infertility following the administration of gonadotoxic cancer treatments. Currently patients do not feel they receive enough information to make informed fertility decisions before treatment. We aim to determine the fertility-related information health care providers and breast cancer survivors consider valuable to include in a Canadian decision aid (Can-DA) for young breast cancer patients by reviewing existing decision support resources. Methods: A qualitative descriptive approach was used to evaluate 6 decision support resources created in other jurisdictions. Using purposeful sampling, 8 multi-disciplinary health care providers and 8 breast cancer survivors from across Canada evaluated 1 to 2 decision support resources in structured interviews. Interviews were conducted in-person and by telephone from March to June 2016 and ranged in length from 30 to 90 minutes. Interviews were transcribed verbatim, organized in NVivo, and analyzed deductively using the pre-defined sections of the interview guide as a framework. Results: Each decision support resource had valuable components to adapt for the Can-DA. Participants valued the inclusion of Canadian-specific and accurate information on resources for additional support and the success rates and cost ranges of fertility preservation procedures. There were mixed views on the impact and value of including in-depth fertility information such as adoption and other fertility-related options after treatment. Discrepancies were also seen on the value of personal stories and an explicit values clarification exercise. There was consensus on the inclusion of only pertinent fertility-related information that does not replicate information in supplementary patient education material to avoid overwhelming patients. Conclusions: The evaluation provided valuable insight on the information and design features to consider for the Can-DA. Findings will be used in combination with the International Patient Decision Aid Standards criteria to ensure the Can-DA meets the fertility information needs of young breast cancer patients in Canada.
Clinical trials networks and enrollment of historically underrepresented populations in medical oncology trials
Authors: J. L. Berkowitz, A. Fernandez, R. A. Dichmann, K. A. Kennedy, B. DiCarlo
Journal: Journal of Clinical Oncology (2009)

e20598 Background: Oncology research is limited by the very low number of patients accrued into clinical trials. Clinical trials networks may help to overcome this limitation by allowing investigations designed through academic centers to be available to patients seen in community practices that are far from these centers. This allows for increased accrual and access for these patients while potentially increasing the pace of progress in clinical oncology research. Methods: In this study, we attempted to determine the effect that clinical trials networks can have on the accrual of cancer patients into clinical investigations. We retrospectively analyzed the records from 2002–2008 of a private practice located over 150 miles from an academic center for accrual into trials. This practice is a member of a clinical trials network affiliated with a major academic cancer center. Accrued patients were divided into subgroups based upon type of malignancy, ethnicity and whether or not they were elderly. In addition, from 2007–2008, the percentage of patients accrued into trials relative to the total number treated onsite was calculated and compared to national averages. Results: In this period, a total of 139 patients at this practice were accrued into clinical trials. By malignancy, they were as follows: breast 36%, colorectal 22%, lung 13%, prostate 8.4%, gastric and lymphoma each 3.0%, pancreatic 1.8%, melanoma 1.2% and ovarian 0.6%. The other 18 patients were in trials for either chemotherapy related anemia 7.8% or bony metastases 3.0%. Of the 139 patients, 45% were elderly and 16% were Hispanic, both markedly higher than national averages. For 2007–2008, 12% of patients that received on site treatment were accrued on to trials. For lung, colorectal, and breast cancer, the number of patients on trial as a percentage of all treated onsite were also higher than the national averages. Conclusions: Clinical trial networks allow a higher percentage of total patients to be accrued than the national average and greatly enhance the potential for both minority and elderly enrollment, two populations that have been historically underrepresented in major clinical trials. It may also help to accelerate the progress of medical oncology research towards better treatments for all patients. No significant financial relationships to disclose.
Neo/adjuvant doxorubicin (A) and ifosfamide (I) versus gemcitabine (G) and docetaxel (T) in patients (PTS) with localized, high risk soft tissue sarcoma (STS): A randomized phase II comparative effectiveness trial.
Authors: Elizabeth J. Davis, Rashmi Chugh, Lili Zhao, J. Sybil Biermann, Sandra L. Wong, Mary Uan-Sian Feng, David Robert Lucas, D'Andra Featherstone, Denise Reinke, Mark M. Zalupski, Scott Schuetze
Journal: Journal of Clinical Oncology (2013)

10524 Background: Approximately 50% of pts with localized, &gt;5 cm, high grade STS develop metastatic disease. Although controversial, adjuvant chemotherapy has demonstrated improved disease-free (DFS) and overall survival (OS). AI can cause significant toxicities that often lead to hospitalization. GT is active in metastatic STS pts and as compared to AI has a favorable schedule and toxicity profile. Methods: In a single-institution phase II study, pts with localized, resectable, high grade STS &gt;5 cm were randomized to receive AI or GT. Pts were stratified by neo- or adjuvant treatment and extremity or non-extremity tumor. Pts received A (75 mg/m2 over 48 hrs) and I (2.5 g/m2/d on D1-3) or G (900 mg/m2 over 90 min on D1,8) and T (100 mg/m2 on D8), both arms with GCSF, for 4 cycles unless progression. Radiation was given after chemotherapy. The primary endpoint of the trial was hospitalization rate during chemotherapy and was compared using a chi square test and multiple logistic regression adjusting for other variables. The trial was powered to detect a reduction in hospitalization rate from 35% to 10% using GT. Survival functions were estimated using Kaplan-Meier method. Results: 84 pts were enrolled from 11/04-8/12 with 80 pts evaluable. The median age is 56 yrs (19-76) and tumor size is 7.8 cm (3.2-25). 55 pts received neoadjuvant therapy and 48 had extremity STS. In the AI arm, 13/37 (35%) pts were hospitalized vs. 11/43 (26%) in the GT arm (p=0.25). The most frequent reason for hospitalization in AI arm was febrile neutropenia (7 events) and in GT arm was hypersensitivity reaction (4 events). The median DFS of pts treated with AI vs GT is 24 months vs not reached, respectively; median follow up is 30 (1-87) months. The 2-year DFS rate is 53% (SD 9%) in the AI arm vs. 71% (SD 7%) in the GT arm and remains marginally significant after adjusting for age, gender, neoadjuvant therapy, tumor site and size (p=0.054). OS rates are not significantly different between arms. Conclusions: Hospitalization rate was not significantly lower with GT compared to AI, although toxicity profile was different. DFS but not OS is marginally improved with GT. Clinical trial information: NCT00189137.
Breast cancer care redesign as an approach to streamline survivorship care: Outcomes and challenges.
Authors: Kathryn Elizabeth Post, Barbara L. Smith, Alphonse G. Taghian, Steven J. Isakoff, Jeffrey M. Peppercorn, Beverly Moy
Journal: Journal of Clinical Oncology (2017)

9 Background: Optimal follow up care for the 3.1 million breast cancer (BC) survivors in the United States has not been definitively determined. ASCO and NCCN recommend that early stage BC patients have a history and physical by their oncology or primary care provider every 3 to 6 months in the first three years post treatment. Additional visits have not been shown to improve outcomes. However, many patients are seen more frequently, leading to increased healthcare costs. In this context, we developed and implemented a BC care redesign algorithm (BCCRA) to reduce redundant follow up. Methods: The BCCRA multidisciplinary team recommended BC survivors be seen by an oncology provider every 6 months for the first five years post treatment and annually thereafter. Retrospective chart review was conducted to evaluate BCCRA adherence from November 2014 to November of 2015. Patients were deemed ineligible if there was a medically necessary reason for visits outside of the BCCRA such as reconstruction, ongoing treatment or clinical trial participation. Eligible charts were analyzed for adherence. For survivors who did not adhere, charts were analyzed for outcome of additional visits. Results: 116 patient charts reviewed and 72 (62.1%) were deemed ineligible. Of the remaining 44 survivors, 26 (59.1 %) adhered and 18 (40.91%) did not adhere. Of the 18 survivors who did not adhere, six had visits due to clinical concern and 12 had visits due to patient or provider preference. Of the 6 patients who had visits for clinical concern, 4 resulted in a change in the patient’s medical management (CMM). Of the 12 patients who had visits due to patient/provider preference, 2 resulted in a CMM. Conclusions: Despite buy-in from a motivated multidisciplinary team, there were challenges to implementing the BCCRA. 62.1% of patients were ineligible and there was a significant proportion of patients/providers who chose more frequent visit schedules. However, the BCCRA had 59.1% adherence which could result in cost reduction and increased flexibility in oncologists’ schedules. Further evaluation of the model is needed to validate these claims.