tbuckley/cabot-search huggingface dataset:
Is obinutuzumab cost-effective in the first-line treatment of CLL?
Authors: David Leroy Veenstra, Carolina M. Reyes, Scott David Ramsey
Journal: Journal of Clinical Oncology (2014)

7052 Background: Obinutuzumab, also known as GA101 (G), is a novel therapy shown to have improved PFS in combination with chlorambucil (GClb) compared to rituximab + chlorambucil (RClb) in the recent CLL-11 trial for previously untreated CLL. The incremental value of G vs. rituximab (R) has not been studied. Methods: Patient outcomes were simulated using a 3-state Markov model that included PFS, progression, and death. The patient population was assumed to be analogous to that studied in the CLL-11 trial. Efficacy parameters were 1) probability of progression, and 2) probability of dying after disease progression. The model parameters were fitted to the observed trial data. Drug utilization and adverse events were incorporated based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs. Sensitivity analyses were conducted to assess uncertainty in the results. Results: Treatment with GClb led to an increase in average life years (+0.61 y) and quality-adjusted life years (QALYs)(+0.56 y) relative to RClb, respectively. The average total costs were similar, with higher drug and adverse event costs for GClb being offset by higher cost of disease progression with RClb. In probabilistic sensitivity analyses, the difference in QALYs ranged from 0.03 to 1.02, and the difference in total cost ranged from approximately -$53,000 to $56,0000. There was an 89% probability that G+Clb was cost-effective at the $100,000 per QALY threshold. Conclusions: Based on the results of the CLL-11 trial, our analysis suggests treatment with GClb compared to RClb is likely cost-effective. Further analyses based on indirect comparisons with other treatment options, as well as updated follow-up data, will help inform coverage and reimbursement policy decisions. Outcome GClb RClb Difference Average life years 5.05 4.44 0.61 Average QALYs 3.36 2.80 0.56 Total drug cost $37,460 $34,875 $2,585 Drug administration $1,134 $803 $330 Supportive care $128 $75 $52 Adverse events $9,851 $6,766 $3,085 Cost of progression $40,004 $46,075 -$6,070 Average total cost $88,577 $88,595 -$18
A multicenter, single-arm evaluation of palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who have experienced CINV during the previous cycle of low emetogenic chemotherapy (LEC).
Authors: A. W. Komorowski, G. R. Morrow, R. Ahmed, D. Cox, P. J. Hesketh
Journal: Journal of Clinical Oncology (2011)

e19587 Background: Patients receiving LEC agents have a 10-30% probability of developing CINV without prophylaxis. Current guidelines recommend one antiemetic agent (generally dexamethasone) for patients (pts) receiving LEC, with a lack of scientific evidence supporting antiemetic use in this population. PALO is a safe and effective antiemetic for pts receiving MEC or HEC, but has not been evaluated in pts receiving LEC. Methods: We conducted a multi-center, single-arm study to evaluate the efficacy of PALO 0.25mg in preventing CINV in pts with confirmed malignant disease who previously experienced either vomiting and/or at least moderate nausea during their last cycle of LEC. PALO was administered prior to the initiation of chemotherapy. Efficacy and safety–including episodes of nausea, retching, and/or vomiting, and use of rescue medication–was assessed from Days 1-6 in patient diaries. The primary outcome was complete response (CR), defined as no emetic episode and no rescue medication for 0-24hrs (acute), >24-120hrs (delayed), and 0-120hrs (overall). Results: A total of 36 pts were enrolled, with 35 pts completing the 5-day study. Patients were mostly female (25, 69.4%), Caucasian (30, 83.3%), with a mean age of 65.0±13.27yrs, and a Karnofsky Performance Status of 82.8±13.86. One patient did not complete verifiable efficacy assessments, with efficacy analysis based on 34 pts. A CR in the acute period (0-24hrs) was noted in 30 pts (88.2%) with no emetic episodes in 31 pts (91.2%). For CINV during the delayed (>24-120hrs) and overall (>0-120hrs) period, 23 pts (67.6%) demonstrated a CR, with no emetic episodes in 27 pts (79.4%). Adverse events (AEs) were seen in 13 pts (36.1%); TEAEs in 12 pts (33.3%)-including decreased appetite, fatigue, headache, and pyrexia (each 2 pts, 5.6%). Conclusions: In patients who experienced CINV on their prior cycle of LEC, palonosetron provided improved CINV prophylaxis in the acute (88% CR) and overall (68% CR) periods, with a safety profile similar to previous trials. Larger studies are warranted to confirm these findings.
Exploratory analysis of adjuvant chemotherapy benefits after preoperative chemoradiotherapy and radical resection for rectal cancer.
Authors: George J. Chang, In Ja Park, Cathy Eng, Y. Nancy You, Scott Kopetz, Michael J. Overman, Miguel A. Rodriguez-Bigas, John Michael Skibber
Journal: Journal of Clinical Oncology (2012)

3556 Background: Evidence regarding adjuvant chemotherapy (CTx) for patients with rectal cancer after preoperative chemoradiotherapy (CXRT) is limited. The aim of study was to explore the relationship between CXRT response and adjuvant CTx for patients with rectal cancer treated by CXRT and radical resection. Methods: We performed a retrospective consecutive cohort study of patients with locally advanced (cStage II-III by EUS, CT, or MRI) rectal carcinoma treated with preoperative CXRT and radical resection, 1993 to 2008. To explore the late effects, we performed a landmark analysis of patients alive without recurrence at 24 months. The duration free from recurrence (FFR) was compared among patients with complete (CR, ypT0N0), intermediate (IR, ypT1-2N0), or poor (PR, ypT3-4 or N+) response according to adjuvant CTx use and type using multivariate Cox regression. Results: A total of 725 patients met criteria and were evaluated. Median follow-up was 69 months (IQR: 39-104 months). 611 patients received adjuvant CTx: 447 with fluoropyrimidine only (FP), and 139 also received oxaliplatin (Ox). Although receipt of adjuvant chemotherapy was not associated with 5-year FFR overall, (HR: 0.91, 95% CI: 0.58-1.43), adjuvant therapy did appear to suggest a benefit in the IR group (HR, 0.49; 95%CI, 0.21-1.19). 2-year landmark analysis showed that adjuvant CTx was associated with a significant improvement in FFR among the IR patients only (HR, 0.28; 95% CI, 0.08-1.00, p=0.04). Among PR patients FP alone did not improve FFR (HR, 1.22; 95% CI, 0.7-2.12) but the addition of Ox was associated with a non-significant reversal in the direction of the effect (HR, 0.53; 95% CI, 0.16-1.79). Conclusions: In this exploratory analysis, the addition of adjuvant FP CTx appeared to favorably affect the duration FFR only for patients with rectal cancer and intermediate response to CXRT followed by radical resection. These data support the investigation of the role for adjuvant fluoropyrimidine therapy among patients with CR or IR and the addition of oxaliplatin for PR patients.
Minimally invasive surgery for resectable pancreatic cancer in the United States: From staging tool to treatment strategy.
Authors: J. K. Smith, E. R. Witkowski, M. M. Murphy, S. Ng, S. A. Shah, J. F. Tseng
Journal: Journal of Clinical Oncology (2011)

243 Background: Debate exists regarding the use of laparoscopy in pancreatic malignancy. The goal of this study was to examine recent laparoscopy use in pancreatic resections for cancer in the US. We hypothesized that there would be two noticeable trends in the use of laparoscopy – the first reflecting staging laparoscopy, the second associated with advancement of laparoscopic pancreatectomy. Methods: The Nationwide Inpatient Sample (NIS), 1998-2007, was used to identify patients ≥ 18 years old with pancreatic cancer who underwent pancreatic resection with or without associated laparoscopy. Patterns of laparoscopy use and correlated outcomes were examined. Results: Among 47599 patients (nationally weighted) who underwent resection for pancreatic cancer, 2640 (5.5%) had procedures that included laparoscopy. Yearly trend analyses demonstrated a peak in laparoscopy in 2003 followed by decreased use, then steady increase after 2005. Laparoscopy at time of resection was not significantly associated with decreased complications (p=0.09), but was associated with lower mortality compared to open resection alone (3.2% vs. 5.9%, p = 0.008). On multivariate analysis, independent predictors of increased complications included older age, male sex, higher comorbidity (Charlson) score, urban location, and non-teaching hospital. For increased risk of death, predictors were older age, male sex, Charlson &gt;2, non-teaching hospital, and non-use of laparoscopy. Conclusions: Trends in the use of laparoscopy during pancreatic resections for cancer suggest initial increased use in the early 2000's following published staging recommendations, with a subsequent decrease contemporaneous with improving imaging techniques. A recent upward trend is likely associated with increased attempts at minimally-invasive resection. The use of laparoscopy is not associated with any difference in complication rate following surgery and is associated with improved perioperative survival. The effects of patient factors, selection, and volume status on minimally invasive pancreatectomy outcomes warrant further investigation. No significant financial relationships to disclose.
A phase I clinical study of weekly heptaplatin and paclitaxel in previously treated patients with advanced solid tumor
Authors: K. H. Jung, D. H. Lee, H. K. Kim, J. Y. Han, H. S. Lim, S. Y. Ju, I. J. Jang, Y. S. Park, J. Ro, J. S. Lee
Journal: Journal of Clinical Oncology (2005)

2039 Background: On a 4-week schedule, the maximal tolerated dose (MTD) for single heptaplatin (H), a less toxic platinum analog, was 480 mg/m2 with recommended dose at 360 mg/m2 (Kim NK et al. Cancer 2001;91:1549–56). We conducted this study to establish the MTD and dose-limiting toxicity (DLT) of weekly administration of H in combination with weekly paclitaxel (P) in previously treated patients (pts) with advanced solid tumor. Methods: Patients with advanced solid tumor, age 20–65, ECOG PS 0–1, 1 or more prior chemotherapy regimens but no prior exposure to platinum or taxanes, and adequate organ function were eligible. P 60 mg/m2 was given first i.v. over 1 hr followed by H i.v. over 1 hr on days 1, 8, and 15, every 4 weeks. Each cohort of 3 pts were treated with escalating doses of H at 120, 150, 200, 250, 300, 350, 400 and up to 450 mg/m2. The DLT and MTD pertaining to first cycle only were obtained and serial blood samples were drawn for H and P pharmacokinetics (PK) during the first cycle. Results: Of 30 pts enrolled, 27 pts were evaluable for toxicity. The DLT was G3 proteinuria, which was noted in 2 of 6 pts at the dose level 450 mg/m2 of H. The MTD was H 400 mg/m2 in combination with P 60 mg/m2. Other significant toxicities were G3/4 neutropenia in 11, G3 thrombocytopenia in 3, G3 constipation, anorexia, and elevated liver enzyme in one patient each. Six of 18 non-small cell lung cancer (NSCLC), 1 of 4 breast cancer and 2 of 2 gastric cancer patients achieved objective tumor responses (PR). PK analysis is in progress. Conclusions: The recommended dose of weekly H is 400 mg/m2 combined with weekly P 60 mg/m2. Further phase II studies of this combination regimen are warranted, particularly in NSCLC and gastric cancer. (Supported in part by SK Pharma and NCC grant 0210140) No significant financial relationships to disclose.
Causes of urban-rural disparities in adjuvant chemotherapy (AC) for rectal cancer (RC).
Authors: Khodadad Rasool Javaheri, Ali Moghaddamjou, Caroline Speers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

e14603 Background: While urban-rural differences in cancer care are well described, the etiology of these disparities is unclear. Our aims were to 1) characterize differences in AC use based on community size and 2) determine if such disparities are mediated through variations in driving distance (DD) and travel time (TT) to closest cancer center. Methods: Patients diagnosed with stage 2 and 3 RC from 1999 to 2009 and referred to any 1 of 5 regional cancer centers in British Columbia were reviewed. Communities were classified as rural, small urban, moderate urban and large urban based on census data. Using zip codes and a distance matrix application interface, DD and TT to the closest cancer center were determined and categorized into quartiles. Stepwise logistic regression models were constructed to explore AC use based on urban vs rural communities, adjusting for DD and TT. Results: A total of 3,017 patients were identified: median age was 67 years (IQR 58-75), 64% were men and 58% received AC. Patients were distributed across various communities: rural 36%; small urban 12%; moderate urban 13%; and large urban 39%. There were no differences in baseline patient and disease characteristics based on community size (all p&gt;0.05). Compared to patients in large urban centers, those living in rural, small urban and moderate urban areas were less likely to be treated with AC (62 vs 49 vs 54 vs 58%, respectively, p&lt;0.001). Likewise, DD and TT were shortest for large urban and longest for rural residents (both p&lt;0.001). In multivariate analyses that controlled for confounders, urban-rural disparities in receipt of AC persisted, but these differences significantly diminished after adjusting for DD, TT, or both (Table). Conclusions: Urban-rural disparities in AC use is partly mediated by commute. Strategic distribution of cancer services that reduce DD and TT to cancer centers may improve access to AC for a number of RC patients who are living in smaller communities. [Table: see text]
Phase II trial of sorafenib (S [BAY 43–9006]) in metastatic melanoma (MM) including detection of BRAF with mutant specific-PCR (MS-PCR) and altered proliferation pathways-final outcome analysis
Authors: C. J. Min, L. F. Liebes, J. Escalon, A. Hamilton, H. Yee, M. T. Buckley, J. J. Wright, I. Osman, D. Polsky, A. C. Pavlick
Journal: Journal of Clinical Oncology (2008)

9072 Background: This is a completed outcome analysis of a phase II trial of S in MM which aimed to determine if treatment (tx) with S altered tumor proliferation,and induced differential anti-tumor responses (resp) in wt or mutB-Raf MM. Mutation detection was performed using a newly developed fluorescent based mutant-specific PCR assay (MS-PCR). Methods: Biopsy (bx)-accessible, untreated MM with measurable disease (RECIST). Stratification:Tumor BRAF status at codon V600 by routine PCR sequencing and MS-PCR. Tx: BAY 400 mg po BID D1–28 q4w. Serial studies: Repeat bx on day 28 for ki-67, cyclin-D1 and ERK; serum collagen cryptic epitopes (epi); re-imaging every 2 cycles; pts treated until progression (PD). Follow-up analysis done on trial completion. Results: 37 pts (11-M1a, 10-M1b, 16-M1c) enrolled. Routine BRAF sequencing yielded 32 wt and 5 mut. MSPCR yielded 22 wt and 15 mut. Median age: 68 (range 22–91); LDH ≥ 1.5 x nl in 12. Toxicity: Gr I diarrhea (7), alopecia (4), rash (6), mucositis (muc) (4), nausea (4), pain (4), hand-foot(h/f) (2); Gr II HTN (4), fatigue (2), muc (1), rash (3), pain (3), h/f (2); Gr III h/f (1), rash (1), fatigue (1), intestinal perforation (1). Tox identical in both groups. Resp: mutBRAF -1 PR (nodes and subcutaneous masses) and 4 PD; wtBRAF -2 PR, 6 SD and 12 PD after 2 cycles. Assessment incomplete in 12 ( 8 early PD, 1 tox drop-out, 1 withdrew prior to tx and 1 no eval tumor). Epi decreased with resp lasting 16–32 w; biopsies demonstrated down regulation of tumor ki-67, erk and cyclin-D1 in PRs and SD. 6 pts with nodular mel of head or acral, all mutBRAF died of brain mets in < 9m. 20 pts with superficial spreading or lentigo maligna died from PD between 5 and 14 months. 11 remain alive with disease- 5wt (1 nodular) and 6mutBRAF (f/u 6–28 m). Conclusions: S monotherapy is minimally active with few short-term resp in both mu and wt B-Raf MM. Down- regulation of proliferation markers was demonstrated, and MS-PCR improved the detection of muBRAF. In this small pt subset, it appears that nodular melanomas of the head or acral origin, are predominantly mutBRAF and quickly metastasize to brain. Supported by NCI N01-CM17103 and TRI 25XS091. No significant financial relationships to disclose.
Clinical significance of peritoneal cytology including cell block method and immunohistochemical analysis in pretherapeutic diagnosis of histological subtype for excluding clear cell and mucinous adenocarcinoma from eligibility for neoadjuvant chemotherapy
Authors: T. Matsumoto, M. Hiura, N. Teramoto, T. Yamamoto, Y. Shiroyama, J. Wroblewski, T. Yokoyama, T. Nogawa
Journal: Journal of Clinical Oncology (2008)

16566 Background: Several clinical trials of neoadjuvant chemotherapy for advanced ovarian cancer have been conducted. However, clear cell and mucinous adenocarcinoma should be excluded from the eligible criteria, because these two histological subtypes are resistant to chemotherapy, and the completeness of cytoreduction is the most prognostic factor in survival. In this study, we verified the significance of peritoneal cytology with cell block method and immunohistochemical (IHC) analysis in the pretherapeutic diagnosis of histological subtype in advanced ovarian cancer. Methods: Forty-one patients with advanced epithelial ovarian or primary peritoneal cancer, consisting of 8 serous (S), 9 endometrioid (E), 5 clear cell (C), 14 mucinous (M) and 5 mixed epithelial tumors, treated between 1/2006 and 12/2007 were analyzed. In 27 patients, only conventional cytology technique was performed; in 14 patients, cell block preparation method was also used. IHC staining of estrogen receptor (ER), mutant p53, cytokeratin 20 (CK20), vimentin and periodic acid-Schiff stain (PAS) was performed in the cytology and/or cell block specimens. Results: In conventional peritoneal cytology, the incidence of positive cytology was 63.0% (17/27). Adding cell block method and IHC staining increased the incidence of positive cytology (85.7%, 12/14). PAS was positive in 25% S (2/8), 33% E (3/9), 100% C (5/5) and 100% M (14/14); ER in 63% S (5/8), 100% E (9/9), 0% C (0/5) and 36% M (5/14); p53 in 75% S (6/8), 11% E (1/9), 0% C (0/5) and 0% M (0/14); Vimentin in 0% S (0/8), 100% E (9/9), 60% C (3/5) and 36% M (5/14); CK20 in 0% S (0/8), 0% E (0/9), 0% C (0/5) and 29% M (4/14). Using this IHC panel, the percentage of correct pretherapeutic diagnoses of histological subtype is 95.1% (39/41). Conclusions: Peritoneal cytology with cell block method and IHC staining of ER, p53 and PAS makes pretherapeutic diagnosis of histological subtype more accurate, and may be useful for individualizing treatment in advanced ovarian cancer patients. No significant financial relationships to disclose.
Five-year overall survival (OS) in non-metastatic androgen-independent prostate cancer (AIPC) patients (pts) treated with nilutamide (N), vaccine (V), and combination therapy
Authors: R. A. Madan, J. L. Gulley, W. L. Dahut, S. M. Steinberg, D. J. Liewehr, J. Schlom, P. M. Arlen
Journal: Journal of Clinical Oncology (2007)

3066 Introduction: There is no standard treatment for pts with non-metastatic AIPC (D0.5).We previously performed the first randomized study in this pt population involving N,V, and combination therapy. To our knowledge this report is the first prospective analysis of OS data in pts with stage D0.5 AIPC. Methods: The initial study randomized 21 pts to treatment with N and 21 pts to treatment with V. The V was an admixture containing a vaccinia vector with the gene for PSA combined with vaccinia containing the costimulatory molecule B7.1. As part of this V strategy, pts also received monthly boosts of fowlpox-PSA with GM-CSF and IL-2 with all vaccinations. Pts who developed rising serum PSA levels on either arm could cross-over to receive both V and N. Initial data demonstrated a clinical benefit in pts treated with combination V and N. Pts characteristics were reviewed and OS was determined using the social security death index. Actuarial analyses of the data using the Kaplan-Meier method were performed. Results: The OS from on-study date in all randomized pts was 4.6 years (yrs) with 3yr OS=71% and 5yr OS=48%. There was no difference in OS in all pts based on Gleason Score (GS) or PSA at diagnosis (dx), orchiectomy, radical prostatectomy, or radiation therapy. However, a subgroup analysis showed a trend to improved OS for pts treated with V alone or V+N (compared to N alone or N+V), who had GS &lt;7 (p=0.18), PSA&lt;20 (p=0.077), and PSA doubling time&lt;3 months (p=0.14). Comparing OS in the study arms: Conclusion: Although these results were not statistically significant due to small cohort sizes, there was a clear trend in both 3yr and 5yr OS in the pts who received V first and crossed-over to V+N, as compared with the reciprocal scheduling of N followed by N+V. A randomized trial at the NCI will compare androgen deprivation therapy (ADT) alone vs ADT plus vaccine to further study the benefits of combination therapy in this population. [Table: see text] No significant financial relationships to disclose.
Clinicopathological features of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) in Japanese patients.
Authors: Akihito Kawazoe, Kohei Shitara, Masaaki Noguchi, Shota Fukuoka, Yasutoshi Kuboki, Hideaki Bando, Wataru Okamoto, Takashi Kojima, Toshihiko Doi, Atsushi Ohtsu, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2016)

629 Background: Recently, anti-programmed death 1 (PD-1) antibody has shown promising efficacy in a phase II trial for patients with microsatellite instability-high (MSI-H) tumors, especially in those with metastatic colorectal cancer (mCRC). Currently, several clinical trials of anti-PD-1 antibody for patients with MSI-H mCRC are ongoing. However, little is known about the frequencies and clinicopathological features of MSI-H mCRC in Japanese patients. Methods: Patients with histologically confirmed adenocarcinoma of mCRC were eligible for this observational study. MSI status was analyzed in tumors using the MSI Analysis System (Promega) composed of 5 mononucleotide markers. KRAS, NRAS, BRAF and PIK3CA mutations were also evaluated using the multiplex kit. Results: A total of 232 patients were enrolled until August 31, 2015, of which MSI-H was detected in 5 patients (2.1%). Among five patients with MSI-H mCRC, median age was 45 years (28-75), four had tumors on right-sided colon, five had moderately differentiated adenocarcinoma, one had poorly differentiated adenocarcinoma, and three had stage IV disease at presentation. Overall survival for patients with MSI-H mCRC from the start of first-line systemic chemotherapy ranged from 8.1 to 62.0 month. All five patients with MSI-H mCRC had RAS wild-type tumors and two had BRAF V600E mutation. One patient with MSI-H mCRC was enrolled in a phase II trial of anti-PD-1 antibody. Conclusions: MSI-H mCRC is rare in Japanese patients. A large scale nationwide cancer genome screening project together with MSI status is required to evaluate more detailed clinicopathological features and facilitate the enrollment of patients with MSI-H mCRC for clinical trials with anti-PD-1 antibody.