tbuckley/cabot-search huggingface dataset:
5-year follow up for 72 metastatic melanoma patients treated with eltrapuldencel-T (CLBS20) vaccine.
Authors: Robert O. Dillman, Carol DePriest
Journal: Journal of Clinical Oncology (2016)

3090 Background: CLBS20 is a patient-specific therapeutic vaccine consisting of autologous dendritic cells loaded with antigens from irradiated cells from an autologous tumor cell line. It potentially presents the entire repertoire of unique antigens resulting from nonsynonymous mutations in a patient’s self-renewing melanoma cells. In previously reported single arm and randomized phase 2 trials, CLBS was associated with a 72% 2-year overall survival (OS). In the randomized trial median OS for CLBS20-treated patients was more than twice that for a vaccine consisting of irradiated autologous tumor cells. Mild local injection site reactions was the most common toxicity. Methods: During 2001 to 2011 72 patients with stage 4 or recurrent stage 3 melanoma were treated with CLBS20 (Clinicaltrials.gov NCT00948480 & NCT00436930). Each had a metastatic melanoma lesion surgically resected, from which a tumor cell line was established, cells from which were incubated with autologous dendritic cells to produce the vaccine that was injected s.c. in 500 micrograms sargramostim (GM-CSF) weekly x 3 weeks and monthly x 5 months (mos). This report summarizes long-term survival data for all CLBS20-treated patients from date of first injection. Results: There were 45 men and 27 women. Median age is 52 years (17 to 83). Tumor sources were 37-lymph node, 15-soft tissue, 20-viscera. Prior therapies included 72-surgery, 41-chemotherapy, 33-Interleukin-2, 30-interferon alpha, 24-GM-CSF, 19-radiation therapy (RT), and 15-RT for brain metastases. All 33 surviving patients were followed 5 years; none were lost to follow up. Median OS is 45.6 mos; 5-year OS is 46%. Median progression free survival (PFS) is 4.4 mos, 5-year PFS is 19%. The 20 patients with recurrent stage 3, have a 70% 5-year OS, median PFS 19.8 mos, and 35% 5-year PFS. For the 52 patients with stage 4, median OS is 41.0 mos, 5-year OS is 36%, and median PFS is 3.8 mos. One patient with refractory progressive measurable disease experienced a delayed complete response that was ongoing at 5 years. Conclusions: CLBS20 is associated with encouraging 5-year overall survival. Because of its unique mechanism of action and absence of toxicity, it should be evaluated further in similar patients. Clinical trial information: NCT00948480. Clinical trial information: NCT00436930.
Impact of clinical stage at diagnosis on outcomes with nivolumab in patients with lung cancer.
Authors: Surabhi Pathak, Vatsala Katiyar, Aakash Putta, Barbara Yim, Thomas E. Lad
Journal: Journal of Clinical Oncology (2018)

e21104 Background: Clinical stage at diagnosis determines prognosis in lung cancer. One third of patients are metastatic at diagnosis with median survival of 1 year. Lately, survival has improved with introduction of immune checkpoint inhibitors. We aim to evaluate differences in outcomes with Nivolumab among patients with non-small cell lung cancer (NSCLC) that are metastatic at diagnosis (ML) compared to those that are non-metastatic at diagnosis and later progress (NML). Methods: We retrospectively reviewed charts of NSCLC patients treated with Nivolumab at our center between 2015-2017. Incomplete charts were excluded. Forty two met the inclusion criteria (ML = 19, NML = 23). Data was analyzed using Fischer exact, Mann-Whitney U tests & Kaplan Meier analysis. Results: Median age was 59 yrs in ML and 56 yrs in NML. NML had 69% stage III & 21% stage II at diagnosis. ML had 68% men vs.56% in NML (p = 0.4), 74% smokers vs. 91% in NML(p = 0.02). Non-squamous histology comprised 79% in ML vs.87% in NML (p = 0.1). Median time to metastases in NML was 13 months. Metastases to bone were present in 63% vs. 17% (p = 0.01), brain in 26% vs. 13% (p = 0.03), liver in 42% vs. 8% (p = 0.001), adrenal in 21% vs. 22% (p = 1), lung in 42% vs. 35 % (p = 0.3) in ML vs. NML. Nivolumab was second line treatment in 95.4% and third line in rest. Median time from metastatic diagnosis to Nivolumab was 8 vs 15 months (p < 0.05), median number of Nivolumab doses were 5 vs. 10 (p = 0.06) in ML vs. NML. Pneumonitis requiring steroids occurred in 5% vs. 13%(p = 0.08), thyroid derangement in 21% vs. 17%(p = 0.5) in ML vs. NML. Response rate was 42% vs. 43% (p = 1) in ML vs NML. Median progression free survival from Nivolumab was 5 [95%CI: 0-13] vs. 7 [95%CI: 0-16] months (p = 0.4) in ML vs. NML. Median overall survival from metastatic diagnosis was 16 [95%CI: 16.4-41.5] vs. 29 [95%CI: 0.4-31] months (p = 0.01) for ML vs. NML respectively. Conclusions: Lung cancer patients with metastases at diagnosis have higher tumor burden and poor overall survival compared to patients that progress from initial non-metastatic disease. Nivolumab improves overall survival however difference between the two groups remain significant. This distinction may be considered when studying therapeutic strategies in advanced lung cancer.
EGFR mutation signature in lung adenocarcinoma.
Authors: Wisut Lamlertthon, Jared Weiss, Matthew Wilkerson, Michele C Hayward, David N. Hayes
Journal: Journal of Clinical Oncology (2016)

e23264 Background: The study goals were to characterize and evaluate an EGFR mutation signature developed from the gene expression datasets of lung adenocarcinoma (LAD) patients. Methods: Three LAD patient cohorts with tumor mRNA expression data were utilized. Training datasets comprised 192 patients were analyzed with Significant Analysis of Microarray. The false discovery rate was set at 1% or less. Differentially expressed genes were used to make a new EGFR mutation signature that has been validated in a combined independent datasets. LAD molecular subtypes and clinical data were associated with the signature. Results: A new EGFR mutation signature composed of 1020 genes was identified. Six hundred ninety genes were overexpressed whereas 330 genes were underexpressed. EGFR and ROS1 were on the list of overexpressed genes with fold change of 2.0 and 1.5, respectively, while KRAS and MYC were on the underexpressed list with the same fold change of 0.6. The EGFR mutation signature had good operating characteristics to predict EGFR mutation status in both the training and validation sets. Having a close relationship to the terminal respiratory unit subtype of LAD, the signature also related to better survival outcome. Conclusions: The EGFR mutation signature is valid and reproducible. It elucidates a particular biology that is not exclusively found in patients with EGFR mutation.
Randomized, double-blind, phase 2 study of S-1 plus oxaliplatin (SOX) with or without ramucirumab (RAM) as first-line therapy followed by paclitaxel plus RAM as second-line therapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma (AGC).
Authors: Kei Muro, Takaki Yoshikawa, Kohei Shitara, Do-Youn Oh, Yoon-Koo Kang, Hyun Cheol Chung, Toshihiro Kudo, Keisho Chin, Shigenori Kadowaki, Yasuo Hamamoto, Shuichi Hironaka, Kazuhiro Yoshida, Chia-Jui Yen, Yasushi Omuro, Li-Yuan Bai, Kaijiro Maeda, Akichika Ozeki, Reigetsu Yoshikawa, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2018)

4036 Background: RAM (a human IgG1 antibody against vascular endothelial growth factor receptor-2) plus paclitaxel has been found to improve overall survival compared with paclitaxel alone as second-line therapy in patients with AGC. This Asian phase 2 study (RAINSTORM) assessed whether adding RAM to SOX as first-line therapy could improve progression-free survival (PFS). Methods: Chemotherapy-naive patients with AGC were randomized to receive SOX (S-1: 80-120 mg/day, twice daily, Days 1-14; oxaliplatin: 100 mg/m2, Day 1) with RAM (8 mg/kg, Days 1, 8) or placebo (PBO; Days 1, 8) in Part A (21-day cycle); patients received paclitaxel (80 mg/m2, Days 1, 8, 15) and RAM (8 mg/kg, Days 1, 15) in Part B (28-day cycle). PFS (primary endpoint), objective response rate (ORR), disease control rate (DCR), and safety for Part A are reported. The PFS hazard ratio (HR) was estimated using a stratified Cox regression model, with a stratified log-rank test P-value of < 0.2 interpreted as RAM+SOX being a useful regimen for first-line therapy in patients with AGC. Results: RAM+SOX (n = 96) did not show an improvement in PFS compared with PBO+SOX (n = 93) (median PFS: RAM+SOX, 6.34 months; PBO+SOX, 6.74 months; HR [80% CI]: 1.07 [0.86, 1.33]; P = 0.698). Among patients with measurable disease, the ORR was 58.2% and 50.0% (odds ratio [80% CI]: 1.37 [0.84, 2.24]; P = 0.402), and the DCR was 90.9% and 87.0% (odds ratio [80% CI]: 1.53 [0.68, 3.43]; P = 0.501), in the RAM+SOX (n = 55) and PBO+SOX (n = 54) arms, respectively. The most common treatment-emergent adverse events in both arms were peripheral sensory neuropathy (RAM+SOX: 58.3%; PBO+SOX: 75.3%), decreased appetite (56.3%; 62.4%), and nausea (56.3%; 39.8%). The most common adverse events of special interest in the RAM+SOX arm (vs PBO+SOX arm) were bleeding/hemorrhage events (37.5% vs 23.7%), hypertension (29.2% vs 12.9%), and proteinuria (25.0% vs 15.1%). Conclusions: Addition of RAM using a new scheduling regimen (8 mg/kg, Days 1 and 8 every 21 days) to a standard SOX regimen did not improve PFS in patients with AGC. Clinical trial information: NCT02539225.
PG2 injection, a novel botanical drug approved for improving cancer-related fatigue among advanced cancer patients under standard palliative care: A double blind, multi-center, randomized phase IV study.
Authors: Cheng-Hsu Wang, Yuen-Liang Lai, Cheng-Yao Lin, Jen-Shi Chen, Ching-Liang Ho, Kun-Ming Rau, Jo-Ting Tsai, Cheng-Shyong Chang, Su-Peng Yeh
Journal: Journal of Clinical Oncology (2018)

10091 Background: Cancer-related fatigue (CRF) is one of the most frequent and debilitating symptoms in 60% to 90% of patients with advanced cancer. The fatigue experienced by cancer patients can not only deteriorate patient quality of life, but also affect treatment efficacy and survival rate. PG2 injection developed by PhytoHealth Co., Taiwan with Astragulus Polysaccharides as API is the only drug approved by Taiwan Food and Drug Administration (TFDA) for relieving CRF in patients with advanced cancer. To further explore the effect of PG2 injection at lower dose, we recruited more patients in the current study and observe the effect of PG2 injection in 2 doses. Methods: Patients with advanced cancer receiving standard palliative care (SPC) with moderate to severe CRF (Score of the Brief Fatigue Inventory-Taiwan (BFI-T)≥4) were enrolled. Patients were randomized at a 1:1 ratio into two arms of PG2 injection treatment: 500mg dose or 250mg dose (both were prepared in 500ml saline and injected 3 times per week for 4 weeks) for two cycles. Fatigue improvement response rates (FIRR) were analyzed at the end of the first cycle to determine the efficacy of the two PG2 doses. Improvement of BFI-T score for more than 10% is considered as effective for relieving CRF. Results: Three hundred and ten patients were enrolled in this study. Two hundred and fourteen patients were included in the ITT population, including 111 subjects in high dose group and 103 subjects in low dose group. Results showed that improvement in fatigue scores by at least 10%, 20%, 30%, and 40% was observed in 65.07%, 46.60%, 34.95%, and 26.61% of subjects receiving 250 mg PG2 injection after one treatment cycle when compared to the baseline; in 500 mg group, fatigue score improvement by at least 10%, 20%, 30%, and 40% was observed in 65.77%, 51.35%, 34.23%, and 18.92% of subjects after one PG2 treatment cycle when compared to the baseline. Conclusions: This study demonstrates that more than 60% of subjects showed at least 10% improvement in fatigue score when compared to baseline after both 250mg and500mg PG2 treatments. Clinical trial information: NCT01720550. Clinical trial information: NCT01720550.
Low-fat dietary pattern and all cancer mortality in the Women's Health Initiative (WHI) randomized trial.
Authors: Rowan T. Chlebowski, Garnet L Anderson, JoAnn E Manson, Ross L Prentice, Aaron K Aragaki, Snetselaar Linda, Shirley AA Beresford, Lewis H Kuller, Karen Johnson, Dorothy Lane, Juhua Luo, Thomas E Rohan, Li Jiao, Ana Barac, Catherine Womack, Mace Coday, Mridul Datta, Cynthia A. Thomson
Journal: Journal of Clinical Oncology (2018)

1500 Background: In the Women’s Health Initiative randomized (WHI) Dietary Modification (DM) primary prevention trial, after 16.1 years median follow-up, implementation of a low-fat dietary pattern significantly reduced deaths after breast cancer. Mortality from other cancer sites has not been reported. Methods: To determine low-fat dietary pattern influence on deaths from and after breast cancer and other cancers during 8.5 years (median) dietary intervention and now with 17.1 years (median) cumulative follow-up, 48,835 postmenopausal women with no prior cancer, aged 50-79, were randomized at 40 US clinical centers from 1993-1998 to dietary intervention (DM-I) (40%, n = 19,541) to reduce fat intake to 20% of energy and increase fruits, vegetables and grains intake, or usual diet comparison (DM-C) (60%, n = 29,294). DM-I influence on breast, colorectal, endometrium and ovarian cancers alone and as a composite were prospectively determined primary analyses. Results: During dietary intervention, deaths after breast cancer was the only statistically significant cancer mortality finding. During cumulative follow-up with 3,867 deaths after all cancers, significant reduction in deaths after breast cancer continued in the DM-I group (HR 0.85 95% CI 0.74-0.99, P = 0.03) especially in subgroup with waist circumference > = 88 cm (HR 0.78 95% CI 0.64-0.95). Deaths after pancreatic cancer were somewhat lower in the DM-I group (HR 0.89 95% CI 0.70 -1.13, not significant). In addition, in no other cancer or cancer composite group was a dietary intervention effect on death from or after cancer seen (see table). Conclusions: Adoption of a low-fat dietary pattern led to a lower incidence of deaths after breast cancer. No reduction in mortality from other cancer sites was seen. Clinical trial information: NCT00000611.Deaths from cause after cancer DM-I* DM-C* HR (95% CI) P-value Primary analysis Deaths after breast cancer 280(0.098) 507(0.12) 0.85(0.74,0.99) 0.03 Death after colorectal cancer 164 (0.057) 228(0.052) 1.10(0.90,1.35) 0.34 Death after ovarian cancer 92(0.032) 143(0.033) 0.98(0.75,1.27) 0.87 Death after endometrial cancer 69(0.042) 98(0.039) 1.07(0.79,1.46) 0.66
Safety of resuming anti-PD-1 (aPD1) in patients (pts) with immune-related adverse events (irAEs) during combined anti-CTLA-4 (aCTLA4) and aPD1 in metastatic melanoma (MM).
Authors: Megan Pollack, Allison Shayna Betof, Katherine Rappazzo, Ian Valentine, Zeynep Eroglu, Douglas Buckner Johnson, Alexander Noor Shoushtari
Journal: Journal of Clinical Oncology (2017)

9544 Background: Combination aPD1 and aCTLA4 has demonstrated greater response rates (RR) than aPD1 alone in MM. However, aPD1 + aCTLA4 also leads to more frequent and severe irAEs compared to aPD1. The safety of resuming aPD1 following these irAEs is not known. We characterized the safety and efficacy of resuming aPD1 following severe irAEs during aPD1 + aCTLA4 in pts with MM. Methods: We retrospectively reviewed mm pts from 3 academic centers who had a severe irAE with aPD1 + aCTLA4 (defined as CTCAE v4.03 G3-4 or leading to early discontinuation of aPD1 + aCTLA4) and who resumed aPD1 thereafter. We assessed for frequency, timing, and spectrum of irAEs as well as RR, progression free survival (PFS) and overall survival (OS). Results: We identified 64 pts who received aPD1 + aCTLA4 for a median of 2 doses (range, 1-4). The most frequent irAEs that led to aPD1 + aCTLA4 discontinuation were: colitis (36%), hepatitis (23%), hypophysitis (8%), pneumonitis (5%), nephritis (3%), neurologic complications (3%), and pancreatitis (3%); eight pts (13%) had &gt; 1 concurrent severe irAEs. aPD1 was resumed at a median of 55 days after last dose of aCTLA4 + aPD1 (range, 17-289); 23% experienced recurrence of the same irAE with aPD1 monotherapy, 16% experienced a distinct irAE, and 60% did not experience any severe irAE after resuming aPD1. Hepatitis recurred in 6 of 18 pts, pancreatitis in 2 of 2, dermatitis in 1 of 4, nephritis in 1 of 2, pneumonitis in 1 of 3, hypophysitis in 1 of 5, and colitis in 1 of 27; the grade of these recurrent irAEs was: 46% grade 1-2, 33% grade 3, 13% grade 4, and 7% grade 5 (n = 1). One death from irAEs occurred related to Toxic Epidermal Necrolysis (TEN). No difference was observed in time prior to resuming aPD1 in those that had recurrent irAEs vs. those without (median 56 days each). The RR in this cohort was 73% (30% CR; 44% PR); median PFS (range, 2.2-not reached (NR)) and OS (range, 2.4-NR) were not reached. Conclusions: In our experience, pts who resume aPD1 following irAEs with aPD1 + aCTLA4 exhibit variable toxicity profiles with most experiencing no irAEs, but a minority experiencing severe or life-threatening irAEs. We observed excellent efficacy in this cohort.
Thin composite wire strut, durable polymer-coated (Resolute Onyx) versus ultrathin cobalt–chromium strut, bioresorbable polymer-coated (Orsiro) drug-eluting stents in allcomers with coronary artery disease (BIONYX): an international, single-blind, randomised non-inferiority trial
Authors: Clemens von Birgelen, Paolo Zocca, Rosaly A Buiten, Gillian A J Jessurun, Carl E Schotborgh, Ariel Roguin, Peter W Danse, Edouard Benit, Adel Aminian, K Gert van Houwelingen, Rutger L Anthonio, Martin G Stoel, Samer Somi, Marc Hartmann, Gerard C M Linssen, Carine J M Doggen, Marlies M Kok
Journal: The Lancet (2018)
Initiation and shift of antidiabetic therapy and pancreatic cancer.
Authors: Philippe Autier, Matteo Franchi, Maria Bota, Agnès Leclercq, Joeri Guillaume, Nancy Van Damme, Giovanni Corrao, Christian Partensky, Mathieu Boniol, Peter Boyle
Journal: Journal of Clinical Oncology (2017)

4126 Background: Concerns have been raised on the risk of pancreatic cancer associated with specific anti-diabetic therapies. We have examined the risk of pancreatic cancer among patients with diabetes prescribed with an oral anti-diabetic drug (OAD) or an incretin drug (DPP4i and GLP-1 RA) or insulin. Methods: The public health insurance databases of Belgium and of Lombardy Region, Italy include nearly 100% of the population living in these countries. We created within these databases two cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) during 01/07/2008-31/12/2013 in Belgium and during 01/01/2008-31/12/2012 in Lombardy Region. The risk of pancreatic cancer after prescription of an anti-diabetic drug was evaluated using multivariate adjusted Cox models including time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled using fixed effects meta-analyses. Results: Results in both cohorts were similar. Among those patients prescribed an OAD, 45% of pancreatic cancers occurred within the 6 months following first prescription, 20% in months 7 to 12 after first prescription and proportions decreased progressively during follow-up. The aHR of pancreatic cancer among subjects prescribed an incretin compared to an OAD was 2.14 [95% CI, 1.71 to 2.67]. The aHR decreased from 3.35 [CI, 2.32 to 4.84] in the first 3 months after first incretin prescription, 2.12 [CI, 1.22 to 3.66] in months 3 to 5.9, 1.95 [CI, 1.20 to 3.16] in months 6 to 11.9, to 1.69 [CI, 1.12 to 2.55] after 12 months. The risk of pancreatic cancer among subjects who were subsequently prescribed insulin was 6.89 [CI, 6.05 to 7.85]. The time from OAD prescription to a shift to incretins or to insulin was significantly lower in patients who were subsequently diagnosed with a pancreatic cancer. Conclusions: The increased risk of pancreatic cancer associated with anti-diabetic therapies could be the consequence of an occult pancreatic cancer that provokes diabetes (reverse causation bias). The search for an occult pancreatic cancer in subjects with newly diagnosed diabetes or patients shifting to more potent anti-diabetic therapy may lead to earlier detection of this cancer.
Efficacy and safety of vitamin K with sorafenib combination treatment against hepatocellular carcinoma: Open-label, randomized phase II study.
Authors: Yoshimichi Haruna, Atsuo Inoue, Seiichi Kawamoto
Journal: Journal of Clinical Oncology (2017)

e15665 Background: Some animal studies showed that vitamin K enhances anti-cancer action of sorafenib for hepatocellular carcinoma (HCC). Our previous examination suggested that it might be because the vitamin K suppresses des-γ-carboxy prothrombin (DCP) production of tumor cells under ischemic status caused by sorafenib. The DCP is known as a tumor growth factor and a tumor angiogenesis factor. In order to clarify the efficacy and safety of vitamin K dosing in sorafenib treatment, we have performed a single center, open label, randomized, phase 2 study. Methods: Forty-four patients with advanced HCC were studied. They were randomly assigned in a 1:1 ratio, to receive vitamin K + sorafenib or to receive sorafenib alone, stratified according to macrovascular invasion and/or extrahepatic spread. The anti-cancer outcome was evaluated by modified RECIST. Results: There was no significant difference between the two groups in baseline characteristics (gender, age, Child-Pugh status and background liver disease). The progression-free survival (PFS) was significantly prolonged in the vitamin K + sorafenib group compared with sorafenib alone group (median time 3.7 months vs. 1.5 months, P = 0.001, hazard ratio 0.35). The disease control rates were 55% in vitamin K + sorafenib group and 18% in sorafenib alone group (P = 0.012). On the other hand, median overall survival (OS) times were 12 months in vitamin K + sorafenib group and 11.5 months in sorafenib alone group (P = 0.27, hazard ratio 0.67). However, 5 patients (23%) of 22 survived for more than 21 months in the vitamin K + sorafenib group, while one (5%) of 22 did in sorafenib alone group. There was no significant difference in incidence of adverse events between the two groups. Conclusions: The vitamin K dosing safely improved anti-cancer outcome of sorafenib treatment against advanced HCC. Clinical trial information: 000007855.