tbuckley/cabot-search huggingface dataset:
A single-arm trial of panitumumab in cetuximab refractory KRAS wild-type colorectal cancer.
Authors: R. C. Wadlow, A. F. Hezel, B. M. Wolpin, J. N. Allen, L. S. Blaszkowsky, E. L. Kwak, R. Wang, A. X. Zhu, D. P. Ryan, J. W. Clark
Journal: Journal of Clinical Oncology (2011)

428 Background: While FOLFOX or FOLFIRI with bevacizumab are the standard first-line regimens in the treatment of metastatic colorectal cancer, a role for epidermal growth factor receptor inhibitiion in KRAS wild-type colorectal cancer has been established in the second and third line setting. Cetuximab is a chimeric antibody that consists of approximately 30% murine protein, and panitumumab is a fully human monoclonal antibody. Correspondingly, the rates of severe hypersensitivity reactions are somewhat increased with cetuximab (3%) compared to panitumumab (1%). Presently, cetuximab is typically used in combination with irinotecan in the second or third line setting, and panitumumab is occasionally substituted if hypersensitivity occurs. The value of panitumumab as a salvage agent in cetuximab-resistant colorectal cancer is unknown. Methods: Panitumumab (6 mg/kg every 14 days) was administered to patients with KRAS wild-type metastatic colorectal cancer that had progressed on prior cetuximab. Treatment was continued until disease progression, death, inability to tolerate panitumumab, or study withdrawal. The primary endpoint was response rate (RR). Twenty patients were enrolled in the first stage and, if at least one responded, 12 additional patients were to be enrolled in a second stage. This two-stage design tested the null hypothesis that the RR is less than or equal to 1% versus greater than or equal to 10% with a type I error of 3.6% and 80% power. Blood samples were collected at baseline and prior to cycles 2 and 3 to evaluate for the presence of anti-cetuximab and anti-panitumumab antibodies using the Biacore immunoassay. Results: 22 patients with ECOG PS 0-2 were treated for a median of two cycles. The best response was stable disease (45%) and the RR was 0%. There were a total of 266 toxicities reported, the majority of which were mild (n = 184, 69%) or moderate (n = 63, 24%) in severity. There were 19 grade 3 and 0 grade 4 toxicities. Median overall survival was 1.9 months. Immunologic data will be reported at the time of presentation. Conclusions: Panitumumab is not active as salvage therapy for patients with cetuximab-resistant, KRAS wild-type metastatic colorectal cancer. [Table: see text]
Referral practices of medical oncologists to palliative care for patients with metastatic non-small cell lung cancer (NSCLC).
Authors: Emily Feld, Leora Horn, Sharon E. Phillips
Journal: Journal of Clinical Oncology (2016)

108 Background: Early implementation of palliative care has shown to improve quality of life and prolong survival in pts with metastatic NSCLC. We sought to investigate the attitudes and referral practices among medical oncologists treating pts with metastatic NSCLC. Methods: Participants were identified through the IASLC 2015 membership directory. All participants were contacted via email to complete an 18-question online survey that included demographic variables as well as questions on referral practice and attitudes regarding the role of palliative care in the treatment of metastatic NSCLC pts. Results: The response rate was 31% (93/303). The majority of participants (94%) practice in an academic setting and 57% had no prior palliative care training. 88% of oncologists report easy access to palliative care providers and 94% have an affiliated palliative care practice within their institution. 83% believe there is definitive evidence in the literature supporting the benefit of early palliative care; however, 40% feel this evidence supports only improved quality of life, not prolonged survival. 58% of oncologists agree that metastatic NSCLC pts should be referred to palliative care early in their disease course. In practice, however, they refer 19% of pts to palliative care at the time of first treatment initiation and this only increases to 38% when considering all referrals made when pts are actively receiving chemotherapy. Reasons for not referring pts include lack of symptoms (56%), belief that oncologists can manage palliative care needs independently (46%), not wanting to burden pts with appointments (41%), concern that referral may not be well received by pts (38%), and long wait times (20%). Reasons for referral include inadequately managed pain (97%), no further treatment options (70%), weak support network (71%), depression/anxiety (68%), other cancer-related symptoms (69%), dwindling treatment options (66%), and lack of time to address palliative care needs (58%). Conclusions: While most oncologists acknowledge the benefit of early palliative care consultation for metastatic NSCLC pts, a minority of pts are referred and strategies to improve referrals are needed.
A phase I trial of cabozantinib (XL184) and gemcitabine in advanced pancreatic cancer.
Authors: David Bing Zhen, Kent A. Griffith, Joshua Michael Ruch, Meredith Morgan, Edward Jae-hoon Kim, Vaibhav Sahai, Diane M. Simeone, Mark Zalupski
Journal: Journal of Clinical Oncology (2016)

334 Background: Hepatocyte growth factor (HGF) and its receptor (c-Met) are activated in pancreatic ductal adenocarcinoma (PDAC). Preclinical data showed a combination of cabozantinib (cabo) and gemcitabine (gem) improved tumor control through inhibition of c-Met. We sought to determine the maximum tolerated dose (MTD) of cabo and gem in patients with advanced PDAC. Methods: Patients with unresectable or metastatic PDAC with ≤1 prior treatment and adequate organ function/performance status were eligible. Cabo was given orally once daily for 7 days and continued with gem infused IV over 30 min on days 1, 8, and 15 of a 28 day schedule. Doses were assigned in accordance with a Time to Event Continual Reassessment Method (TITE-CRM) per table below. Primary endpoint was MTD, defined as the highest dose level at which ≤25% of patients incurred a dose-limiting toxicity (DLT) in the first 35 days of therapy. Secondary endpoints included response rate, progression-free survival (PFS), and overall survival (OS). Results: Twelve patients were treated from July 2012 – May 2015. Median number of cycles given was 3 (range: 1-6). MTD was not determined. The probability of DLT was &gt;25% for all dose levels attempted. Four of 10 evaluable patients experienced DLT (shown in table below), including grade 3 ALT/AST elevations (n=3) and thrombocytopenia (n=2). Five of 6 patients who continued therapy beyond cycle 2 incurred at least one grade 3 adverse event. Three patients had a partial response, but each discontinued therapy due to toxicity. Median PFS and OS were 4.7 (95% CI: 1.4 – 9.7) and 10.1 months (95% CI: 3.6 – 20.6), respectively, in treated patients. Conclusions: While the combination of cabo and gem demonstrated activity in PDAC, this regimen is impractical due to DLT at low doses and continuing toxicities despite dose reductions and schedule changes. Clinical trial information: NCT01663272. [Table: see text]
Nationwide underestimation of low-grade invasive ovarian carcinomas: Population-based evidence in SEER.
Authors: P. M. Grimley, K. Apostle, H. A. Young, D. E. Henson
Journal: Journal of Clinical Oncology (2011)

e15523 Background: Identifiers of stage and grade for ovarian serous carcinomas (OSC) can inform both clinical trials and individual patient management, but assignment of this data was missing for 12-23% of cases recently accessioned by the National Cancer Institute’s SEER program. We used descriptive epidemiology to probe for possible explanations. Methods: Incidence rates (IR) for 15,656 cases of histologically confirmed invasive OSC in SEER (2000-2007) were stratified by age, racial-ethnic background and region to compare stage (FIGO), grade (ICD-O-3), tumor size or missing identifiers. Results: Exponential graphs of age-specific IR for cases missing stage consistently aligned with graphs for cases diagnosed in advanced stage regardless of grade. Conversely, graphs of age-specific IR for histologically examined cases with missing grade aligned with graphs for cases of low grade regardless of tumor stage or size identifications. Exponential IR plots of cases missing stage vs. early stage cases, and of cases missing grade vs. high grade cases, demonstrated reproducible graph curve crossings at age >60 years for missing stage, and age <45 years for missing grade. Such age-dependent crossings, characteristic of IR ratio shifts (qualitative age interactions), proved robust in demographic or regional population subsets representing heterogeneities in mean IR (p>0.05). Conclusions: The patterns of missing stage or grade assignments found for OSC were non-random and not evidently linked. Respective biases towards advanced stage or low grade reflect at least two preconditions which constrained the choice of cases for comprehensive oncologic evaluation. Of particular interest, the true IR of low grade OSC in advanced stage may be up to twice those currently represented in SEER. Increasing evidence of molecular biologic differences in the carcinogenic pathways of low and high grade OSC may have yet unrecognized clinical implications. The large scale censoring of unassigned case data, as reflected in SEER, could compromise promising efforts to investigate OSC progression, develop prognostic indices based upon molecular profiles, or individualize therapy.
A comparison of simple single-item measures and the common toxicity criteria in detecting the onset of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer
Authors: R. F. Morton, J. A. Sloan, A. Grothey, D. J. Sargent, H. McLeod, E. M. Green, C. Fuchs, R. K. Ramanathan, S. K. Williamson, R. M. Goldberg
Journal: Journal of Clinical Oncology (2005)

8087 Background: Peripheral neuropathy (PN) is a common and intrusive side effect of chemotherapy. The assessment of PN is typically done via the common toxicity criteria (CTC). To date there is no optimal measure of peripheral neuropathy. We developed simple single-item numerical analogue scale (NAS) assessments for the unique oxaliplatin-induced PN. The purpose of this investigation was to asses the relative sensitivity of the CTC and NAS measures in detecting the onset and severity of PN in patients receiving oxaliplatin. Methods: 696 patients randomized to the FOLFOX4 arm of the the practice-changing inter-group/NCCTG study N9741 provided data on the incidence and severity of PN experienced via bi-weekly CTC assessments and NAS measurements taken every 12 weeks. The NAS is a simple measure from 0 representing no PN to 10 representing PN as bad as it can be. A change of 2 points from baseline on the NAS was used as a conservative estimate of a clinically meaningful change in PN. Results: 276 patients (40%) reported a 2 point worsening from baseline in PN via NAS compared to 256 (37%) with a CTC reported grade 2+ PN and 99 (14%) with a CTC reported grade 3+ PN. For those ultimately reporting PN, median dose to onset of a clinically significant worsening of PN via NAS was 424 mg/m2 relative to a dose to grade 2+ (3+) PN of 765 (961) mg/m2 for CTC criteria. This means that patients notice an increase in PN about two or three months earlier via the NAS relative to the CTC. Agreement between CTC grade 2+ (3+) PN and NAS assessment was only 65% (63%) with a Cohen’s Kappa of 0.26 (0.13). The majority of patients reported the 2 point decline in PN via NAS prior to their reported CTC PN event (53% for grade 2+, 83% for grade 3+). Conclusions: The CTC measurement of PN under-reports the incidence and time to onset of PN relative to simple single-item NAS measures. Grade 2 PN via the CTC is a clinically significant problem according to patient ratings on the NAS. In future studies, it is recommended that the CTC be supplemented by patient-reported measures of PN. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi, sanofi-aventis Sanofi, sanofi-aventis
Docetaxel rechallenge in patients with prostate cancer progressing under castration levels of testosterone (PPuCT): A single-center study.
Authors: L. Robert, J. P. Maroto, A. Sebio, C. Martin, J. Palou, G. Sancho, I. Sullivan, P. Murata, A. Stradella, A. Barnadas
Journal: Journal of Clinical Oncology (2011)

e15105 Background: Until recent developments in treatment of PPuCT (cabezitaxel, abiraterone) progressing after docetaxel, second line therapies were scarce. In our Hospital, Docetaxel as first line treatment was delivered for a fixed number of cycles (between 6 and 8) and not limited until toxicity. Our thought was that this approach could offer the patient an opportunity of a rechallenge with docetaxel at progression. Methods: From February 2002 to August 2010, 116 patients (pt) with a median of 69 years old (45-84) initiated first-line treatment with docetaxel for a median of 6-8 cycles. Rechallenge was considered for those patients that achieved with the first line stable disease (clinically or by PSA) at least. Docetaxel rechallenge was offered if patients presented symptomatic progressive disease or a PSA progression >50% over the nadir. Results: Considering as PSA response a decrease of PSA >30% (Bubley), 60 out of 116 pt (51.7%) had a partial response, and 13 pt (11.2%) stable disease. Of those 73 pt with at least stable disease, 40 pt (31%) were rechallenged with docetaxel, after a median interval free of docetaxel of 6.4 months (1.8–27.11). PSA rechallenge`s response rate was partial response in 15 pt (39%) and stable disease in 5 pt (13%). Finally, 9 pt were considered for third re-treatment with docetaxel, providing a PSA response rate of 33.3%. The overall median total docetaxel cycles delivered was 5 (1-21), and 31 pt received 10 or more cycles of docetaxel. Median total cycles for patients retreated once was 12 (6-21) and 18.5 cycles for patients retreated twice (14-21). Median overall survival (95% CI) was 12 months (9.5-14.5) for patients treated once, compared to 25.1m (21-29) for patients retreated. Those patients re-treated once achieved 23.2m (19-26) of OS and those re-treated twice achieved the 29.3m (23.9-35) of OS. Grade 3-4 haemotoxicitiy was <5% and no treatment-related deaths occurred among the patients rechallenged. Conclusions: Rechallenge with docetaxel is feasible and provides further responses in selected patients with prostate cancer. It might be considered for those patients responding to a first line docetaxel that had a tolerable toxicity.
Presentation, clinical behavior, outcomes and therapies for patients with advanced pancreas adenocarcinoma (PAC) who present with or develop ascites.
Authors: Angel Mier Hicks, Eileen Mary O'Reilly, Marinela Capanu, Maeve Aine Lowery, Kenneth H. Yu
Journal: Journal of Clinical Oncology (2016)

209 Background: Ascites develops in a subset of patients with PAC at presentation or as the disease advances. Limited data exist on the prognostic importance of malignant ascites in PAC. Our hypothesis is that this information will provide an understanding of the natural history and facilitate management decisions. Methods: We conducted a retrospective analysis of N = 180 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between January 1, 2009 and December 31, 2014, with PAC and ascites either at presentation or which developed during the disease course. Results: For the 180 patients, overall survival was 15 months. Time from diagnosis to ascites presentation was 11 months and survival time after ascites development was 4 months. Of 62 patients (34%) who had ascitic fluid analyzed, N = 36 (58%) had positive cytology, N = 51 (82%) patients had a serum ascites albumin gradient (SAAG) ≥ 1 and N = 11 (18%) had SAAG &lt; 1.1. Sixty-four (36%) of patients had their ascites managed solely by serial paracenteses. A total of 116 patients required a catheter, from these, N = 108 (93%) had a Tenckhoff catheter, N = 4 (3%) Pleurx catheter, N = 3 (2%) Pigtail catheter and one (1%) a Denver catheter. Eight (4%) patients required two catheters to be placed and N = 6 (3%) Tenckhoff catheters had to be removed. Main observed complications: spontaneous bacterial peritonitis in N = 7 (11%) of patients managed with paracenteses vs. N = 34 (19%) who had a catheter placed, catheter malfunction in N = 8 (4%), acute renal failure in N = 6 (3%). After ascites development N = 79 (44%) of patients received active therapy and N = 101 (56%) patients were managed with supportive care alone. Conclusions: In patients with PAC the presence of ascites is a poor prognostic factor. Serial paracenteses and indwelling catheters are common methods used for alleviating patients’ discomfort. The complication rate was higher with indwelling catheters, primarily associated with infections (e.g. bacterial peritonitis) with low rates of complications occurring related to catheter malfunction, acute renal failure or bowel perforation.
Evaluation of a novel heterologous PrimeBoost immunotherapy in stage III/IV metastatic melanoma patients
Authors: R. E. Hawkins, U. Keilholz, A. Dangoor, A. Harris, C. Ottensmeier, D. Schadendorf, J. Smyth, K. Hoffmann, R. Anderson, G. Pearce
Journal: Journal of Clinical Oncology (2005)

2570 Background: This study evaluates the safety, immunogenicity and clinical response (by RECIST criteria) of increasing doses of DNA plasmid (DNA.Mel3) and MVA viral vector (MVA.Mel3) containing 7 human CTL epitopes from 5 melanoma antigens (Tyrosinase, melan-A, MAGE-1, MAGE-3, NY-ESO-1). Methods: 31 HLA-A2 positive patients with measurable stage III/IV melanoma were enrolled. Immunisations were 3 weeks apart. Epitope-specific CD8+ T cell responses were evaluated using ex vivo tetramer staining and interferon gamma (IFN-γ) ELISPOT assays. Results: At week 16, 20 currently completed patients showed no dose limiting toxicity with only mild to moderate injection site reactions predominantly reported post MVA.Mel3. In the low dose groups (groups 1–3), 8/15 immunologically evaluable patients showed a significant increase of melanA CD8+ tetramer+ T cells. Of these 8, 3 also showed a significant increase of IFN-γ secreting T cells against melanA, tyrosinase leader, and/or NY-ESO-1. One clinical responder, confirmed at week 28, had ELISPOT responses against both melanA and tyrosinase leader. Additionally, of two patients with stable disease at week 16 one showed increases in melanA CD8+ tetramer+ T cells. Conclusions: Low dose heterologous PrimeBoost immunotherapy was safe and stimulated immune responses in >50% of metastatic melanoma patients treated. Immune responses against multiple antigens were observed in the partial clinical responder. Complete 16 week data from the high dose groups (10e8–10e9 pfu) will be available for presentation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oxxon Therapeutics Ltd. Oxxon Therapeutics Ltd.
Assessment of quality of life (QOL) in phase III trials in advanced colorectal cancer (CRC).
Authors: K. Adamowicz, J. Jassem, E. D. Saad
Journal: Journal of Clinical Oncology (2011)

e14072 Background: QOL parameters are often used as endpoints in phase III trials in medical oncology. We assessed the extent to which these parameters had been used in recent studies on CRC and investigated the frequency and correlates of significant QOL gains. Methods: We used the medical subject headings “colorectal neoplasms” and “drug therapy” to search PubMed for the main paper reporting phase III trials on systemic antineoplastic therapies published between 1/1998 and 12/2009 in 10 leading journals (Ann Oncol, Br J Cancer, Cancer, Clin Cancer Res, Eur J Cancer, JCO, JNCI, Lancet Oncol, Lancet and NEJM). We also searched for companion papers reporting on QOL separately. We excluded papers reporting on correlative biology or prognostic factors in isolation from the main trial results. Results: We retrieved 67 trials that enrolled a total of 35,117 evaluable patients in 149 trial arms. The proportion of trials mentioning QOL in the second 6-year period (28.2%) was lower than in the first period (61%; P=0.01). QOL parameters were listed as endpoints in 22 reports (33%), never as primary or co-primary endpoints. The most common instrument used for QOL assessment was QLQ C-30. Formal statistical comparisons involving QOL parameters were reported in 23/67 cases (34%), and a significant difference was found in 7/23 (30%) trials, in 5 cases favoring the experimental arm. QOL was mentioned in the abstract of 19/67 (28%) reports, in 10 cases in the conclusion. Trials with QOL gain included more patients than those without (medians of 572 vs 374), but the difference was not significant. Other associations between gains in QOL and study variables will be presented. Conclusions: QOL has been formally assessed in nearly one-third of contemporary phase III trials in advanced CRC, but this practice seems to be declining. A significant gain in QOL has been found in almost one-third of trials in which such endpoints were analyzed.
Expression of the c-met and HGF in resected hepatocellular carcinoma (rHCC): Correlation with clinicopathological features (CP) and overall survival (OS)
Authors: F. D. Huitzil, M. Y. Sun, M. Capanu, L. H. Blumgart, W. R. Jarnagin, Y. Fong, R. P. DeMatteo, M. I. D’Angelica, M. R. Weiser, G. K. Abou-Alfa
Journal: Journal of Clinical Oncology (2008)

4599 Background: c-met and HGF have been implicated in the development and progression of HCC, however association with CP or OS in pts with HCC is controversial. We determined c-met and HGF mRNA expression in tumor (T) and non-tumoral tissue (NT) in patients (pts) with rHCC; and studied correlation of their expression with CP and OS. Methods: We retrospectively identified 49 pts with rHCC for whom frozen samples of T and NT tissue were available. Tumor c-met/HGF mRNA expression normalized to 18S rRNA expression was determined by RTPCR. T/NT tissue ratio of c-met and HGF mRNA expression was deduced. Validation using immunohistochemistry (IHC) for c-met expression was performed on some samples. CP were recorded and blinded from authors performing the RTPCR. Kruskal-Wallis test and linear models were used for categorical and continuous CP correlation respectively. Results: Pts median age 65, male 65%, cirrhosis 18%, hepatitis B 29%, hepatitis C 9%, and alcohol abuse 26%. Median diameter of the largest lesion was 10.5 cm, satellite nodules 28.6%, bilobar disease 24.5%, portal vein thrombosis 2%, positive margins 10%, microscopic vascular invasion 40%. Pathologic stage: T1 41%, T2 14%, T3 33%, T4 12%. Median relative tumor c-met expression: 3.23 (T/NT ratio 7.1). Median relative tumor HGF expression: 8.13 (T/NT ratio 0.6). c-met expression detected by RTPCR and IHC showed poor correlation. Statistically significant CP correlations are shown in table 1. In general, the higher the c-met and HGF expression, the earlier the stage and more favorable pathologic features. There was no correlation between c-met, HGF and OS. Conclusions: In this cohort of rHCC c-met is overexpressed preferentially in early stage resected disease, however there is no association with OS. The inverse T/NT ratio of HGF expression is possibly explained by the known paracrine production of HGF. Further studies are warranted to evaluate the role of c-met/HGF in the larger cohort of pts with advanced HCC. Correlation of c-met / HGF expression with clinicopathological features Characteristic Direction of the correlation with c-Met expression p Direction of the correlation with HGF expression p T stage Negative 0.002 Negative 0 TNM stage Negative 0.009 Negative 0.011 Largest tumor diameter Negative 0.048 Negative 0.014 Vascular invasion Negative 0.019 Negative 0 Positive resection margin Negative 0.004 Negative 0.011 Abdominal pain Negative 0.027 Negative 0.027 Satellite nodules Negative 0.042 Negative 0.042 Albumin Positive 0.037 AST Negative 0 No significant financial relationships to disclose.