tbuckley/cabot-search huggingface dataset:
Phase 1b/II study of cancer stemness inhibitor napabucasin (BBI-608) in combination with FOLFIRI +/- bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts).
Authors: Johanna C. Bendell, Joleen Marie Hubbard, Bert H. O'Neil, Derek J. Jonker, Alexander Starodub, James D. Peyton, Henry C. Pitot, Thorvardur Ragnar Halfdanarson, Benjamin Rolland Nadeau, John D. Zubkus, Bamidele Adesunloye, William Jeffery Edenfield, Youzhi Li, Wei Li, Axel Grothey, Laura Borodyansky, Chiang Li
Journal: Journal of Clinical Oncology (2017)

3529 Background: Cancer stem cells are considered to be fundamentally important for resistance, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapy and targeted agents. Methods: A phase Ib/II multi-center study in mCRC pts was done to confirm the RP2D and signs of anti-cancer activity of napabucasin in combination with FOLFIRI +/- Bev. Pts received napabucasin 240 mg PO BID with bi-weekly FOLFIRI IV +/- Bev 5 mg/kg until disease progression or other discontinuation criterion. Results: 82 pretreated mCRC pts were enrolled (ITT); including 32 (39%) previously treated with FOLFIRI +/- bev. Of the 82 pts, 48 received FOLFIRI and 34 FOLFIRI plus bev in combination with napabucasin. There was no dose-limiting or unexpected toxicity or significant PK interactions. Most common adverse events (AEs) included grade 1/2 diarrhea, cramping, nausea, vomiting, fatigue and anorexia with grade 4 diarrhea in 1 pt and 27 pts with grade 3 AEs including: diarrhea (15), fatigue (5), dehydration (1), electrolyte imbalance (4), abdominal pain (1), vomiting (1) and weight loss (1), which resolved with dose reduction and supportive care. Disease control (CR+PR+SD) was observed in 55 of 66 pts who received RECIST evaluation (83%), with 1 CR (1.5%), 13 PR (20%) (33-100% regression) and 27 SD with tumor regression (41%). Conclusions: This phase Ib/II study confirmed that napabucasin can be safely combined with FOLFIRI +/- bev, and shows encouraging signs of efficacy in pretreated mCRC pts, including pts previously treated with FOLFIRI +/- bev. Clinical trial information: NCT02024607. [Table: see text]
Risk stratification including FOXO1 fusion status (FOXO1) in patients with rhabdomyosarcoma (RMS) treated on six recent frontline trials: A report from the Children's Oncology Group (COG).
Authors: Emily Hibbitts, Douglas S. Hawkins, Carola A. S. Arndt, Yueh-Yun Chi
Journal: Journal of Clinical Oncology (2017)

10528 Background: Clinical risk factors associated with outcome in children with either localized or metastatic RMS were identified by Meza et al. (2006) and Oberlin et al. (2008). We re-examined risk stratification by adding FOXO1 to traditional clinical prognostic factors in children with localized or metastatic RMS in a large cohort from COG frontline clinical trials. Methods: Data from six COG clinical trials (D9602, D9802, D9803, ARST0331, ARTS0431, ARST0531) accruing previously untreated patients with RMS from 1997 to 2013 yielded 1,853 eligible patients (two studies each for low, intermediate and high risk patients). Survival tree regression for event-free survival (EFS) and overall survival (OS) was conducted to determine prognostic impact of risk factors. Recursively, the factor most strongly associated with outcome was selected for branching and split using a goodness of fit measure. Factors included were age, FOXO1, group, histology, nodal status, number of metastatic sites, primary site, sex, tumor size, and presence of metastases in bone/bone marrow, soft tissue, effusions, lung, distant lymph nodes, and other sites. Results: 5-year overall EFS and OS was 0.67 (SE, 0.01) and 0.77 (SE, 0.01), respectively. Survival trees for EFS and OS found localized versus metastatic at the first split and included FOXO1 as a significant risk factor. Conclusions: FOXO1 improves risk stratification of patients with localized RMS, although histology and pattern of metastases are more predictive for patients with metastatic RMS. Our findings support incorporation of FOXO1 in risk stratified clinical trials. [Table: see text]
The effect of black cohosh on Ki67 levels in DCIS patients.
Authors: Erin Wysong Hofstatter, Amelia Anne Trant, Karen Stavris, Nina Ruth Horowitz, Brigid K. Killelea, Donald R. Lannin, Veronique Neumeister, David L. Rimm, Anees B. Chagpar
Journal: Journal of Clinical Oncology (2018)

e13541 Background: Recent evidence suggests that black cohosh (Cimicifuga racemosa) may prevent and treat breast cancer through anti-proliferative, pro-apoptotic, anti-estrogenic, and anti-inflammatory effects. We sought to determine the efficacy of black cohosh (BC) as a potential chemoprevention agent by evaluating its ability to decrease the cell proliferation biomarker Ki67 in a pre-operative window trial of ductal carcinoma in situ (DCIS) patients. Methods: Patients were treated pre-operatively with commercial standardized isopropanolic black cohosh extract (20 mg orally twice daily) for 2-5 weeks. Ki67 in DCIS regions was measured using automated quantitative immunofluorescence (AQUA) pre- and post-operatively. A sample size of 22 patients, assuming a 10% drop-out rate, was estimated to achieve 91% power to detect a 0.8 standard deviation of difference with a two-sided significance level at 0.05 using Wilcoxon signed-rank test. Eligible subjects were women newly diagnosed with DCIS on core biopsy, prior to definitive excision (NCT01628536). Results: Of 32 patients enrolled, 24 patients were available for Ki67 analysis; 5 patients’ samples were unevaluable by AQUA and 3 patients lacked DCIS post-treatment. Mean duration of BC therapy was 23 days (range; 13-35 days). Among evaluable patients, we found no significant change in Ki67 values in areas of DCIS with pre-operative exposure to BC (Z = -.9714, p = .33), though a downward trend was observed. Eleven of the 32 patients (34%) were found to have invasive disease at the time of surgery, nine of whom had grade 2-3 DCIS at biopsy; these observations are similar to expected DCIS upgrade rates published in the literature. BC was well tolerated; no related adverse events were above grade 1. Conclusions: Pre-operative exposure to BC did not significantly decrease Ki67 in patients with DCIS, although a downward trend was seen. Our findings suggest that BC is safe for use in breast cancer patients and could be explored as a potential chemoprevention agent. Clinical trial information: NCT01628536.Disease # of patients Avg. Ki67 pre Avg. Ki67 post % decrease p-value DCIS 14 1700 1327 21.94 .68 Invasive 10 1413 1076 23.82 .28 All patients 24 1581 1223 22.64 .33
Comparison of abiraterone acetate and docetaxel with androgen deprivation therapy in high-volume metastatic hormone-sensitive prostate cancer (mHSPC): An updated network meta-analysis and cost minimization analysis in China.
Authors: Xin Hu, Xingxing Yao, Chaoyun Li, Yanjun Liu, Tengbin Xiong, Shuli Qu, Jianye Wang
Journal: Journal of Clinical Oncology (2018)

e17008 Background: The recently published network meta-analysis by Wallis demonstrated no statistically significant difference in the overall survival (OS) for men treated with Abiraterone Acetate plus prednisone/prednisolone with ADT (Abi-ADT) versus docetaxel with ADT (Doce-ADT). Our study aims to provide an update of Wallis’study for patients with high-volume mHSPC, and then to perform economic evaluation between Doce-ADT and Abi-ADT in China through a cost-minimization analysis from both the healthcare and the patient perspectives. Methods: English and Chinese database were systematically searched for randomized controlled trials (RCTs) up to November 2017. The Bucher technique for indirect treatment comparison was used to compare PFS in patients treated with Abi-ADT and those with Doce-ADT. A cost-minimization analysis over a lifetime survival projection was conducted. Drug acquisition costs, hospitalization and testing costs, and adverse events treatment costs were derived from the local setting. Results: Overall, 1895 patients from three trials which reported PFS data were included: 354 (18.7%) patients who received Doce-ADT, 597 (31.5%) patients who received Abi-ADT, and 944 (49.8%) patients who received ADT-alone. The pooled hazard ratio (HR) for PFS was 0.56 (95% CI: 0.46-0.67, I2= 0%, 2 trials, 696 patients) for Doce-ADT versus ADT-alone and 0.47 (95% CI: 0.40-0.55, 1 trial, 1,199 patients) for Abi-ADT versus ADT-alone. The indirect comparison demonstrated no statistically significant difference in PFS for Abi-ADT versus Doce-ADT (HR: 0.84, 95% CI: 0.63–1.12). Cost analysis indicated that Doce-ADT cost less than Abi-ADT with potential savings of up to RMB 246,137 and RMB 66,549 per patient from the healthcare perspective and patient perspective. Conclusions: Based on the evidence that there is no significant difference in either PFS or OS between two strategies in the treatment of high-volume mHSPC patients, the cost analysis concludes that Doce-ADT is a cost-saving alternative compared with Abi-ADT in China.
Efficacy, tolerability, and manageability of TAS-102 plus bevacizumab for metastatic colorectal cancer patients in clinical practice.
Authors: Hideki Ishikawa, Koichi Suzuki, Nao Kakizawa, Fumiaki Watanabe, Kosuke Ichida, Yuji Takayama, Taro Fukui, Fumi Hasegawa, Rina Kikugawa, Kazushige Futsuhara, Shingo Tsujinaka, Yasuyuki Miyakura, Hiroshi Noda, Toshiki Rikiyama
Journal: Journal of Clinical Oncology (2018)

e15535 Background: The C-TASK FORCE trial demonstrated that TAS-102 plus bevacizumab might become a potential treatment option for patients with metastatic colorectal cancer (mCRC) in a refractory setting, but so far the benefits of TAS-102 with bevacizumab compared with TAS-102 alone have not been shown in clinical practice. The present study conducted a retrospective review of 45 consecutive mCRC patients treated with TAS-102 with or without bevacizumab. Methods: Thirty-five mg/m2of TAS-102 was given orally twice daily on days 1–5 and 8–12 in a 28-day cycle, and 5 mg/kg of bevacizumab was administered by intravenous infusion for 30 min every 2 weeks. The disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events were compared between patients treated with TAS-102 with or without bevacizumab. Results: Twenty-three consecutive mCRC patients were treated with TAS-102 (TAS) between April 2014 and March 2016, while 22 were treated with TAS-102 plus bevacizumab (TAS + Bmab) between April 2016 and December 2017. The DCR was 22.7% and 61.1% in the TAS and TAS + Bmab groups, respectively. Median PFS was 3.5 months and 5.6 months in the TAS and TAS + Bmab groups, respectively (P= 0.0181). The TAS + Bmab group exhibited a longer median OS time compared with the TAS group (11.5 months vs 6.5 months, respectively; P= 0.0492). The most common grade 3/4 adverse event was neutropenia, which was observed in one patient (4.5%) in the TAS group and six (29%) in the TAS + Bmab group. Grade 3/4 neutropenia in these six patients was well-managed using pegfilgrastim every month. Conclusions: Our data showed that TAS-102 plus bevacizumab was effective, well-tolerated, and manageable for treatment of mCRC patients in a refractory clinical setting.
Economic aspects of nivolumab in non-small cell lung cancer (NSCLC): Lessons from real life.
Authors: Elizabeth Dudnik, Laila Roisman, Jair Bar, Nir Peled, Ariel Hammerman, Sameh Daher, Mor Tal Moskovitz, Sivan Shamai, Ekaterina Hanovich, Alona Zer, Ofer Merimsky, Mira Wollner
Journal: Journal of Clinical Oncology (2017)

e18322 Background: Novel immunotherapy agents' costs have a significant impact on healthcare system budgets. Aside from the cost per dose of the compound, the total treatment cost (TTC) is affected by the duration of treatment (DOT). DOT in real life may differ significantly from that observed in the randomized clinical trials because of the differences in baseline patient characteristics and treatment patterns. Methods: Advanced NSCLC patients (pts) (n=192) treated with nivolumab 3mg/kg q2w (expanded access program/standard of care) at five Israeli cancer centers between January 2015 and March 2016 were included in the analysis. DOT and TTC were assessed in 2 groups (group A: ECOG PS 0/1, n=92; group B: ECOG PS ≥2, n=100). In addition, response for a subgroup of 49 pts was evaluated by RECIST, v.1.1. In this subgroup, DOT and TTC of treatment (Tx) beyond progression (PD) were assessed as well. Nivolumab cost per dose was calculated for a 78 kg pt based on current market price in Israel: 3 mg/kg X 78 kg = 240 mg = 11,250 NIS (2,993 USD). Results: Pt baseline characteristics: median age 67y (range, 41-99); males 68%; smokers 77%; ECOG PS ≥2 52%; Non-squamous/Squamous/NA 78%/19%/3%. 27% of pts continued nivolumab at the time of last follow-up. DOT and TTC are presented in the table below. Conclusions: DOT and TTC are similar for ECOG PS 0/1 and ECOG PS ≥2 pts. Tx beyond PD increases the TTC by 32%. These facts should be taken into consideration when evaluating budget impact of novel immunotherapy agents' implementation into routine practice. [Table: see text]
Fertility-sparing surgery in stage IA2 cervical cancer: Associated factors and long-term survival.
Authors: Mario M. Leitao, Yukio Sonoda, Ginger J. Gardner, Oliver Zivanovic, Nadeem Abu-Rustum, Jill Tseng
Journal: Journal of Clinical Oncology (2016)

e17012 Background: Approximately 40% of cervical cancers are diagnosed between the ages of 20 and 44. Standard therapy for stage IA2 disease consists of non-fertility sparing options. We sought to evaluate the oncologic outcomes of young women with stage IA2 cervical cancer treated with fertility-sparing surgery (FSS). Methods: We queried the SEER database for women younger than age 45 diagnosed with FIGO stage IA2 cervical cancer from 1998-2012 who underwent conization or trachelectomy (defined as FSS) or hysterectomy of any type (defined as non-FSS). Squamous cell, adenocarcinoma and adenosquamous histologies were included. Associated factors and outcomes of FSS vs non-FSS were analyzed. Appropriate univariate and multivariate statistical testing was performed. Results: We identified 1425 women: 245 underwent FSS (conization 85%, trachelectomy 15%) and 1180 underwent non-FSS (simple hysterectomy 53%, modified radical/radical hysterectomy 40%, unspecified hysterectomy 7%). For FSS vs non-FSS, median age was 32 (range, 19-44) vs 37 (range, 22-44) (p < .001), 4% vs 12% of women had grade 3 disease (p < .001), and 23% vs 58% underwent regional lymphadenectomy (p < .001). There were no significant differences in race, marital status, SEER region, histology, or lymph node positivity between the two groups. Those treated with FSS were more likely to be younger (OR 1.14, 95% CI 1.11-1.16) and less likely to have grade 3 disease (OR 0.41, 95% CI 0.18-0.94) than those treated with non-FSS. With a median follow-up of 109 months (range, 0-179), 10-year disease-specific survival (DSS) was 97.6% (SE ± 0.5) for FSS and 98.3% (SE ± 0.7) for non-FSS (p = .12). Lymph node positivity was independently associated with DSS (HR 6.78, 95% CI 1.25-36.76) while FSS was not. When stratified by histology, 10-year DSS for FSS vs non-FSS was as follows: squamous cell, 97.0% vs 98.4% (SE ± 1.3, 0.5; p = .05); adenocarcinoma, 100% vs 98.6% (SE ± 0.0, 1.0; p = .56); and adenosquamous carcinoma, 100% vs 95.1% (SE ± 0.0, 3.4; p = .68). Conclusions: In young women with stage IA2 cervical cancer, DSS is excellent. Treatment with FSS appears to offer comparable oncologic outcomes compared to those treated with non-FSS.
Phase 3 prognostic analysis of the automated bone scan index (aBSI) in men with bone-metastatic castration-resistant prostate cancer (CRPC).
Authors: Andrew J. Armstrong, Lars Edenbrandt, Eva Bondesson, Aseem Anand, Orjan Nordle, Michael Anthony Carducci, Michael J. Morris
Journal: Journal of Clinical Oncology (2017)

5006 Background: Quantitative measures of metastatic bone disease are needed in men with mCRPC. We recently demonstrated the validity/reproducibility of a computational approach to bone scan imaging that employs artificial intelligence called the automated BSI (aBSI), which quantifies the percent of skeletal mass involved by cancer. We aimed to extend the prognostic validation of aBSI in a multinational prospective phase 3 clinical study of men with bone-metastatic CRPC. Methods: Whole-body bone scans were acquired at screening in a placebo-controlled phase 3 trial of men with mCRPC and bone metastases and treated with tasquinimod/placebo (n = 1,245). The prospective aBSI biomarker analysis plan was locked in Sept 2014 prior to treatment unblinding. All scans generated at 241 trial sites in 37 countries were assessed for image quality and analyzed using the EXINI bone BSI v.2 software and were blindly associated with outcomes. Baseline aBSI was evaluated for its independent prognostic association with overall survival (OS), radiographic progression-free survival (rPFS), and symptomatic skeletal related events (SSEs). Results: The aBSI-population (721 pts) was representative of the entire trial population based on patient characteristics at screening and OS outcomes. Median aBSI was 1.07 (SE 0.05). The aBSI-population was divided into quartiles (n = 180-181) with aBSI-levels of 0 - 0.3 (Q1); &gt; 0.3 - 1.1 (Q2); &gt; 1.1 - 4.0 (Q3); and &gt; 4.0 (Q4) and median OS ranging from 35 months (Q1) to 13 mo (Q4) (p &lt; 0.0001). Baseline aBSI was significantly associated with OS (HR 1.2 per doubling of BSI; p &lt; 0.0001) and remained independently associated with OS after adjustment for treatment, PSA, CRP, LDH and albumin. Baseline aBSI was also strongly associated with rPFS (p = 0.0005), time to symptomatic progression (p &lt; 0.0001), and time to SSE (p = 0.001). Conclusions: This analysis represents the first phase 3 evaluation of aBSI as a clinically validated prognostic biomarker for OS, rPFS, and SSEs in men with bone-metastatic CRPC, providing independent prognostic information over commonly measured clinical characteristics. Clinical trial information: NCT01234311.
Rechallenge in advanced GIST progressing to imatinib, sunitinib and regorafenib: An Italian survey.
Authors: Bruno Vincenzi, Margherita Nannini, Giovanni Grignani, Elena Fumagalli, Silvia Gasperoni, Lorenzo D'Ambrosio, Giuseppe Badalamenti, Angelo Paolo Dei Tos, Lorena Incorvaia, Paolo G Casali, Daniele Santini, Giuseppe Tonini, Marco Stellato, Giovanna Catania, Mariella Spalato Ceruso, Maria A. Pantaleo
Journal: Journal of Clinical Oncology (2017)

11038 Background: We retrospectively collected data from metastatic Italian GIST patients treated with imatinib or sunitinib reintroduction after progression to conventional three or four lines of therapy. Methods: 82 eligible advanced GIST patients, previously treated with imatinib, sunitinib and regorafenib, were collected in the present analysis from 6 cancer centres. All patients received all three standard kinase inhibitors. Imatinib dose increase as active second line or 800 mg upfront in exon 9 mutant GIST were allowed. Specific mutations were recorded if available (deletion versus others) and correlated with survival and response according to RECIST 1.1 or CHOI criteria. Results: Seventy-four of 82 patients received Imatinib 400 mg as rechallenge, while 8 patients were treated with sunitinib at personalised dose and schedule according to the physician’s choice. Mutational status was available in all patients and in 68 patients details about type of mutation were achievable. The median follow-up was 13 months (range 1-42 months). The median time to progression (TTP) in patients receiving a rechallenge therapy was 5.4 months (95% CI 1.9-13.5) and Overall Survival (OS) was 10.6 months (95% CI 2.8-26.9). Apparently, in this setting a correlation between mutational status and response rate, TTP or OS was not found. On the contrary, considering only exon 11 mutated patients and comparing patients with deletion vs non deleted ones a significant difference was identified both in terms of TTP and OS (respectively, P = 0.04 and P = 0.02). Conclusions: Our retrospective data confirm that the rechallenge of imatinib or sunitinib is a reasonable option in advanced GIST patients after failure of previous treatments. As expected, imatinib is the most frequently prescribed option in the Italian real-life setting, demonstrating a TTP and OS longer than those observed in previous studies. Also the prognostic value of the specific type of exon 11 KIT mutations has been confirmed in our series.
Evaluation of Spirulina in the supportive treatment associated to palliative chemotherapy in patients with advanced oncologic disease.
Authors: Silvia Regina Graziani, Carolina Graziani Vital, Hezio Jadir Fernandes, Cassia Costa, Fauzia de Fátima Naime, Brigitte M. Van Eyll, Ricardo Oliveira Da Fonseca, Carla Andressa Rodrigues Dias, Ligia Rabello De Almeida, Patricia Massae Marubayashi, Raphael Francisco Azuaga Neto, Aderson Bohadana Coutinho Rodrigues, Jorge Abissamra Filho, Karina Emi Yamada, Maria Stella Sa Granja De Abreu, Tatiana Caldeira Pontes, Dominique Silva, Carlos Elias Fristachi
Journal: Journal of Clinical Oncology (2016)

e21602 Background: The use of phytotherapy as supportive treatment in patients with oncologic disease has been showed as a usual practice controling symptoms related to chemotherapeutic agents. Spirulina is a sweety water algae and a phytotherapeutic agent, which is known in Asia and South America as a dietary supplement, due to its nutritional properties. This study aimed to evaluate the impact of the association of Spirulina in the conventional treatment and the nutritional laboratories parameters in patients with advanced disease receiving palliative chemoterapeutic treatment. Methods: One hundred and twenty patients with solid tumors (breast, lung, GI tract, prostate, malignant melanoma, oropharynx, gynecologic, sarcoma and pancreas cancer) were included, all with Stage IV (TNM Scale) and median age of 62 ± 6 years (40 to 88 years). Treatment consisted with conventional chemotherapy plus Spirulina at 380 mg, twice a day, continuously and before meal. Serum biochemistry as hemoglobin, albumin, C reactive protein were evaluated and also weight gain and the fold of the thumb muscle, before the beginning of treatment and every 3 weeks, with median evaluation of 6 weeks. Results: One hundred and sixteen (97,6%) of patients were evaluated and four came out of treatment due to gastrointestinal intolerance. The average weight gain was 600 g (-1kg to +1.6 kg) being that, seventy patients had stable weight. The fold of the thumb muscle remained stable during the evaluation period, as the hemoglobin levels, with a median count of 10,2 g/dl. The complaints of weakness and malaise improved even with stable levels of hemoglobin. The average lymphocyte count was 950 mm3 (410 to 1400 mm3), albumin levels was 3,2 g/dl (2,1 to 4,1 g/dl) and C reactive protein was 59,4 ng/dl (2 to 140 ng/dl). Conclusions: We conclude that the use of Sipirulina represents an effective alternative in the nutritional support in patients with advanced oncologic disease and also improved the laboratory biomarkers of nutrition.