The outcome of patients with advanced hepatocellular carcinoma (HCC) in pre- and post-sorafenib eras using the SEER database.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 276-276
Author(s):  
Jiahuai Tan ◽  
Minsig Choi ◽  
Philip Agop Philip ◽  
Gregory Dyson ◽  
Anthony Frank Shields ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Number Of Patients ◽  
The Impact

276 Background: HCC is the third most common cause of cancer-related death globally. Prognosis for advanced HCC is dismal due to lack of effective treatment options for the majority of patients who present with advanced disease. Sorafenib was the first agent reported to improve overall survival in patients with good liver function enrolled in phase III clinical trials. However, survival impact of sorafenib on the general population with advanced HCC has not been studied to date. Methods: Sorafenib was approved for patients with advanced HCC and Child-Pugh A liver disease in 2007. We analyzed 2005-2006 and 2008-2009 clinical outcome data from the SEER to compare the impact of this targeted therapy in the population based setting. The Kaplan-Meier method was used to estimate the median survival and 95% confidence intervals (CI). The log-rank test was used to test the difference in survival curves. Cox regression analyses were utilized for the estimation of hazard ratios. Results: We identified 2297 and 2808 stage III and IV HCC cases diagnosed in [2005, 2006] and [2008, 2009], respectively. Seventy-seven percent of the patients were male and the median age was 61 years old for males and 66 for females. The median survival estimates (95% CIs) are 3 (3, 4) months and 4 (4, 4) months for patients diagnosed in [2005, 2006] and [2008, 2009], respectively. The hazard ratio (95% CI) for overall survival comparing [2008, 2009] to [2005, 2006] was 0.92 (0.87, 0.98, p-value = 0.01). We performed multivariable Cox regression modeling and African American patients have a hazard ratio of death [1.14 (1.06, 1.23)] as compared to European American patients. Younger females have a decreased hazard of dying relative to younger men, while older females have an increase hazard of dying relative to older men. Conclusions: The approval of sorafenib treatment produced very modest median survival gain in advanced HCC patients based on SEER population study. However, the small benefit in hazard ratio may have been impacted by small number of patients with advanced HCC who are being treated or are able to be treated with sorafenib in this era.

Phase IIb randomized trial of Pexa-Vec (pexastimogene devacirepvec; JX-594), a targeted oncolytic vaccinia virus, plus best supportive care (BSC) versus BSC alone in patients with advanced hepatocellular carcinoma who have failed sorafenib treatment (TRAVERSE).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4161-TPS4161
Author(s):  
Jeong Heo ◽  
Yee Chao ◽  
Derek J. Jonker ◽  
Ari David Baron ◽  
Francois Habersetzer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Vaccinia Virus ◽  
Median Survival ◽  
Hazard Ratio ◽  
High Dose ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Gm Csf

TPS4161^ Background: Pexa-Vec is a targeted oncolytic and immunotherapeutic vaccinia virus engineered to express human granulocyte-macrophage colony stimulating factor (GM-CSF). Direct oncolysis plus GM-CSF expression stimulates tumor vascular disruption and anti-tumor immunity (Nature Rev Cancer, 2009). Pexa-Vec was well-tolerated in Phase 1 trials and was shown to replicate in metastatic tumors following intratumoral (IT) or intravenous (IV) administration (Lancet Oncol, 2008 and Nature, 2011). A randomized high vs low dose Phase 2 trial in 30 patients with advanced HCC, demonstrated prolonged survival in the high-dose Pexa-Vec arm (median survival 14.1 mo vs. 6.7 mo; Hazard Ratio 0.39, p=0.02) (AASLD Annual Meeting, 2011, LB1). Methods: TRAVERSE is a Phase 2b randomized, open-label, multi-center trial in patients with advanced HCC who have failed sorafenib treatment. Approximately 120 patients will be randomized 2:1 to Pexa-Vec plus BSC versus BSC, respectively. Randomization will be stratified by region (Asian vs. non-Asian); sorafenib intolerant vs refractory; and presence vs absence of extra-hepatic disease. The primary objective is to determine overall survival. Main inclusion criteria are advanced HCC having failed sorafenib (intolerance or radiographic progression during or < 3 months following last sorafenib), Child-Pugh A-B7 (no ascites), acceptable hematologic function. Assuming a median overall survival of 4.0 months with BSC and a target hazard ratio of 0.57 (corresponding to an experimental arm median survival of 7.0 months), 73 events (deaths) will provide 70% power at 1-sided alpha = 0.05 to detect a difference in overall survival between the treatment groups using a stratified logrank test. Patients randomized to Pexa-Vec will receive a dose of 109 plaque forming units (pfu) IV on Day 1 followed by five IT treatments between Day 8 and Week 18. Enrollment has begun on this study with clinical trial registry number of NCT01387555. Clinical trial information: NCT01387555.

Phase IIb randomized trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, plus best supportive care (BSC) versus BSC alone in patients with advanced hepatocellular carcinoma who have failed sorafenib treatment (TRAVERSE).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4152-TPS4152
Author(s):  
James M. Burke ◽  
Caroline Breitbach ◽  
Richard H. Patt ◽  
Riccardo Lencioni ◽  
Michel Homerin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Phase 1 ◽  
Hazard Ratio ◽  
High Dose ◽  
Advanced Hepatocellular Carcinoma ◽  
Clinical Trial Registry ◽  
Logrank Test ◽  
Sorafenib Treatment ◽  
Advanced Hcc

TPS4152 Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus GM-CSF expression stimulates tumor vascular disruption and anti-tumor immunity (Nature Rev Cancer 2009). JX-594 was well-tolerated in Phase 1 trials and was shown to replicate in metastatic tumors following intratumoral (IT) or intravenous (IV) administration (Lancet Oncol 2008 and Nature 2011). A randomized dose-finding Phase 2 trial has been completed with JX-594 in 30 patients with advanced HCC. Treatment with high-dose JX-594 was associated with prolonged survival vs low-dose JX-594 (median survival 14.1 mo vs 6.7 mo; Hazard Ratio 0.39, p=0.02) (AASLD Annual Meeting, 2011, LB1). Methods: TRAVERSE is a Phase 2b randomized, open-label, multi-center trial of JX-594 plus BSC versus BSC in patients with advanced HCC who have failed sorafenib treatment. Approximately 120 patients will be randomized 2:1 to experimental and control arm respectively. Randomization will be stratified by region (Asian vs non-Asian); sorafenib intolerant vs refractory; and presence vs absence of extra-hepatic disease. The primary objective is to determine overall survival in the 2 arms. Assuming a control median overall survival of 4.0 months and a target hazard ratio of 0.57 (corresponding to an experimental arm median survival of 7.0 months), 73 events (deaths) will provide 70% power at 1-sided alpha = 0.05 to detect a difference in overall survival between the treatment groups using a stratified logrank test. Patients randomized to JX-594 will receive a dose of 109 plaque forming units (pfu) IV on Day 1 followed by five IT treatments between Day 8 and Week 18. Main inclusion criteria are advanced HCC having failed sorafenib (intolerance or radiographic progression during or < 3 months following last sorafenib), Child-Pugh A-B7 (no ascites), acceptable hematologic function. Enrollment has begun on this study with clinical trial registry number of NCT01387555.

Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: A randomized, placebo-controlled, double-blind, phase III study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4507-4507 ◽  
Author(s):  
Qiu Li ◽  
Shukui Qin ◽  
Shanzhi Gu ◽  
Xiaoming Chen ◽  
Lizhu Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Chinese Patients ◽  
Biological Behavior ◽  
Advanced Hepatocellular Carcinoma ◽  
Double Blind ◽  
Sorafenib Treatment ◽  
Advanced Hcc

4507 Background: Chinese patients (pts) account for more than 50% of hepatocellular carcinoma (HCC) cases in the world and have special features in etiology, biological behavior, treatment strategy and prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib, an inhibitor targeting vascular endothelial growth factor receptor-2, in Chinese pts with pretreated advanced HCC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 trial done in 31 sites in China, pts with HCC who had received at least one line of systemic therapy (including sorafenib and oxaliplatin-based chemotherapy, which is another first-line standard-of-care in China) and had Child-Pugh liver function class A or B ≤7 points were enrolled. The pts were randomly assigned (2:1) to receive 750 mg apatinib orally once daily or placebo and stratified by ECOG performance status (0 or 1), previous sorafenib treatment (yes or no), and extrahepatic spread and/or macrovascular invasion (yes or no) in 28-day treatment cycles. The primary endpoint was overall survival (OS). Results: Between Apr 01, 2014 and May 03, 2017, 393 pts were randomized and received at least one dose of study treatment (261 in apatinib arm and 132 in placebo arm). The median OS was significantly longer with apatinib than that with placebo (8.7 months [95% CI 7.5-9.8] vs 6.8 months [95% CI 5.7-9.1]; hazard ratio 0.785 [95% CI 0.617-0.998]; p=0.0476). Pts in the apatinib arm also had prolonged median progression free survival (PFS) compared with those in the placebo arm (4.5 months [95% CI 3.9-4.7] vs 1.9 months [95% CI 1.9-2.0]; hazard ratio 0.471 [95% CI 0.369-0.601]; p˂0.0001). The objective response rate was 10.7% (95% CI 7.2-15.1) with apatinib versus 1.5% (95% CI 0.2-5.4) with placebo. Treatment-related adverse events (TRAEs) were reported in 250 (97.3%) pts in the apatinib arm and 92 (70.8%) pts in the placebo arm. The most common TRAEs of grade 3 and 4 were hypertension (71 [27.6%] pts in the apatinib arm vs 3 [2.3%] pts in the placebo arm), hand-foot syndrome (46 [17.9%] vs 0), decreased platelet count (34 [13.2%] vs 1 [0.8%]), and decreased neutrophil count (27 [10.5%] vs 0). 24 (9.3%) pts with apatinib and 13 (10.0%) pts with placebo died due to adverse events, and none were deemed treatment-related by investigators. Conclusions: Apatinib significantly prolonged OS and PFS in Chinese pts with pretreated advanced HCC, and was well tolerated with a manageable safety profile. Clinical trial information: NCT02329860 .

Analysis of prognostic factors in patients with advanced relapsed/refractory NSCLC: Cox regression analysis of a randomized phase III trial comparing docetaxel and paclitaxel poliglumex (PPX)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7040-7040 ◽  
Author(s):  
P. Bonomi ◽  
C. Langer ◽  
M. O’Brien ◽  
K. O’Byrne ◽  
B. Bandstra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Stage Iv ◽  
Tumor Stage ◽  
Phase Iii ◽  
Line Treatment ◽  
Phase Iii Trial ◽  
Cox Regression Analysis ◽  
The Impact

7040 Background: A phase III trial compared PPX to docetaxel as 2nd-line treatment in pts with relapsed/refractory advanced NSCLC (STELLAR 2). While overall survival was similar between arms, the need for supportive measures to manage the effects of myelosuppression was significantly reduced in the PPX arm. The current analysis was performed to evaluate determinants of survival in the 2nd-line treatment of NSCLC. Methods: STELLAR 2 enrolled 849 pts, 427 on PPX and 422 on docetaxel; all patients were included in the analysis. Randomization between the study arms was stratified by tumor stage, performance status (PS), start of frontline chemotherapy (< 4 mo vs more than 4 mo), gender, and prior taxane therapy. Univariate and multivariate Cox regression analyses were performed to evaluate the impact of baseline characteristics on overall survival (OS). Results: At randomization, 29% of pts had received prior taxane, 14% were PS2, 80% had stage IV disease, and 31% had started frontline therapy within the prior 4 months. Risk factors significantly affecting survival as determined by multivariate analysis are listed in the table . These factors were consistent when treatment was added to the model. Prior exposure to taxane was not predictive of survival; tumor stage was a significant univariate predictor (p=0.0349), but had relatively less impact in the multivariate model. Conclusion: These analyses identified several factors associated with reduced survival benefit from standard second line therapy. Consequently, alternative treatment strategies may be necessary in patients with poor prognosis. For example, more tolerable agents may enhance the benefit/toxicity ratio in these patients. [Table: see text] [Table: see text]

A population-based analysis of prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 163-163
Author(s):  
Alan D. Smith ◽  
Winson Y. Cheung
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Elevated Serum ◽  
Advanced Hepatocellular Carcinoma ◽  
Clinical Factors ◽  
Conventional Chemotherapy ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Staging Systems

163 Background: Available clinical prognostic scoring systems for advanced hepatocellular carcinoma (HCC) were developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care for advanced HCC due to its survival benefit. The utility of these prognostic models in the setting of sorafenib is unclear. Our aims were to assess for new prognostic factors in patients treated with sorafenib and compare these with known prognostic systems. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 in British Columbia, Canada and treated with sorafenib at any 1 of 5 regional cancer centers were eligible. Based on the established Okuda, CLIP, Barcelona, and French staging systems, we collected baseline demographic and disease characteristics of patients prior to receipt of sorafenib. Multivariate logistic regression models were constructed to examine for associations between these clinical factors and overall survival. Results: Of 183 patients identified, 152 were evaluable: median age was 63 years, 78% were men, average number of sorafenib treatment was 5.3 cycles, and median overall survival was 9.6 months. The prevalence of hepatitis B, hepatitis C, and alcohol-related liver disease were 32%, 15%, and 11%, respectively. Univariate analyses showed that poor performance status, presence of clinical ascites, as well as elevated serum AST, GGT, ALP, bilirubin and platelet levels were each associated with worse overall survival (all p<0.05). In multivariate analyses, however, none of these clinical factors continued to be independently predictive of outcome (all p>0.05). Conclusions: Traditional clinical prognostic factors developed in the era of conventional chemotherapy do not appear to have the same prognostic utility in this contemporary Western cohort of advanced HCC patients treated with sorafenib. This observation underscores the need to identify molecular biomarkers that provide better prognostic information.

Survival among colorectal cancer patients with a history of previous cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16146-e16146
Author(s):  
Sandi Pruitt ◽  
David E. Gerber ◽  
Hong Zhu ◽  
Daniel Heitjan ◽  
Bhumika Maddineni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Population Based ◽  
Competing Risk ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

e16146 Background: A growing number of patients with colorectal cancer (CRC) have survived a previous cancer. Although little is known about their prognosis, this population is frequently excluded from clinical trials. We examined the impact of previous cancer on overall and cancer-specific survival in a population-based cohort of patients diagnosed with incident CRC. Methods: We identified patients aged ≥66 years and diagnosed with CRC between 2005-2015 in linked SEER-Medicare data. For patients with and without previous cancer, we estimated overall survival using Cox regression and cause-specific survival using competing risk regression, separately by CRC stage, while adjusting for numerous covariates and competing risk of death from previous cancer, other causes, or the incident CRC. Results: Of 112,769 CRC patients diagnosed with incident CRC, 15,935 (14.1%) had a previous cancer – most commonly prostate (32.9%) or breast (19.4%) cancer, with many 7505 (47.1%) diagnosed ≤5 years of CRC. For all CRC stages except IV in which there was no significant difference in survival, patients with previous cancer had modestly worse overall survival (hazard ratios from fully adjusted models range from 1.11-1.28 across stages; see Table). This survival disadvantage was driven by deaths due to previous cancer and other causes. Notably, most patients with previous cancer had improved CRC-specific survival. Conclusions: CRC patients who have survived a previous cancer have generally worse overall survival but superior CRC-specific survival. This evidence should be considered concurrently with concerns about trial generalizability, low accrual, and heterogeneity of participants when determining exclusion criteria. [Table: see text]

Pattern of progression in advanced HCC treated with ramucirumab/placebo: Results from two randomized phase III trials (REACH/REACH-2).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 544-544
Author(s):  
Maria Reig ◽  
Peter R. Galle ◽  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Josep M. Llovet ◽  
...  
Keyword(s):  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Cox Models ◽  
Poor Prognostic Factor ◽  
Advanced Hcc ◽  
Pooled Data ◽  
Phase Iii Trials ◽  
Ecog Ps ◽  
Post Hoc ◽  
The Impact

544 Background: REACH (NCT01140347) and REACH-2 (NCT02435433) studied ramucirumab (RAM) in pts with advanced hepatocellular carcinoma (HCC) following sorafenib; REACH-2 enrolled pts with baseline alpha-fetoprotein (AFP) ≥400 ng/mL, and met its primary endpoint of overall survival (OS) for RAM vs placebo. This post-hoc analysis examined radiological progression patterns (RPP) incidence every 6 weeks per RECIST v1.1, and if RPP were related to OS and post-progression survival (PPS). Methods: Pts with advanced HCC, Child-Pugh A, and ECOG PS 0-1 with prior sorafenib were randomized (REACH 1:1; REACH-2 2:1) to receive RAM 8 mg/kg or placebo Q2W. Among pts with ≥1 RPP (new extrahepatic lesion [NEH], new intrahepatic lesion [NIH], extrahepatic growth [EHG], or intrahepatic growth [IHG]), results were analyzed by trial and for pooled individual patient data of REACH-2 and REACH (AFP ≥400 ng/mL). Cox models evaluated treatment effect of RPP on OS, and prognostic implications of RPP on OS (adjusting baseline ECOG PS, AFP, macrovascular invasion, arm) and on PPS (adjusting ECOG PS, AFP at progression). Results: RPP incidence in the pooled population was: NEH 39%; NIH 24%; EHG 39%; IHG 37%. When examining NEH vs other RPP, PPS was worse among those with NEH in REACH (HR 2.33, 95% CI 1.51, 3.60), REACH-2 (HR 1.49, 95% CI 0.72, 3.08), and the pooled data (HR 1.75, 95% CI 1.12, 2.74). Use of post-discontinuation therapy may have influenced results. OS was also significantly reduced in those with NEH across studies (Table). RAM provided OS benefit in the pooled population, including pts with NEH (HR 0.56, 95% CI 0.39, 0.80). Conclusions: Acknowledging limitations of post-randomization RPP analysis, the emergence of NEH on RAM or placebo may be an independent poor prognostic factor for PPS. The impact of RAM on OS was consistent across all RPP subgroups. Clinical trial information: NCT01140347 and NCT02435433. [Table: see text]

The use of cabozantinib in advanced hepatocellular carcinoma (HCC): Hong Kong multi-center experience.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 316-316
Author(s):  
Yawen Dong ◽  
Thomas Wai-Tong Leung ◽  
Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hong Kong ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Real Life ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

316 Background: In the phase III CELESTIAL trial, cabozantinib showed significant improvement in overall survival with good tolerability in advanced HCC population. We aimed to evaluate the efficacy, survival and tolerability of cabozatinib in advanced hepatocellular carcinoma (HCC) patients in a real life setting. Methods: Between February 2018 and October 2019, consecutive advanced HCC patients who received cabozatinib alone or in combination at University of Hong Kong Health System hospitals were analysed. Cabozantinib was administered at 60 mg continuously daily. Objective response rate (ORR), time-to-progression (TTP), overall survival (OS), and tolerability were evaluated. Results: Overall, 22 patients were included. The median age was 57.1 years (range 48.5-58.6). All patients except one were hepatitis B carriers. More than 80% of the patients had underlying Child-Pugh A cirrhosis. Most patients had metastatic disease (95.5%). More than 70% of patients received cabozantinib beyond second-line, and most of the patients had prior exposure to tyrosine kinase inhibitor (TKI) and/or immunotherapy. The median time from the start of first-line systemic treatment to the start of cabozantinib was 11.2 months. Cabozantinib was administered to 11 patients (50%) as single agent, while the other half received cabozantinib in combination with mostly immune checkpoint inhibitors. The median follow-up was 7.6 months. The table below shows the ORR. The overall median TTP and OS were 4.2 and 8.90 months, respectively. Interestingly, among those who received single agent cabozantinib, the median OS was 5.36 months in contrast to 12.32 months in the patients received combination. Overall, 90.9% of patients experienced treatment related adverse events (TRAEs) with transient liver function occurred in nearly 50% patients. Nevertheless, Grade 3/4 TRAEs was only 12%. Conclusions: Our present study showed that the use of cabozatinib in advanced HCC patients had good anti-tumour activity and survival benefits with acceptable toxicity profile. [Table: see text]

Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA4509-LBA4509 ◽  
Author(s):  
P. A. Philip ◽  
J. Benedetti ◽  
C. Fenoglio-Preiser ◽  
M. Zalupski ◽  
H. Lenz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Clinically Significant

LBA4509 Background: Epidermal growth factor receptor [EGFR] pathway is a rational target for therapeutic intervention. This study tested the efficacy of an anti-EGFR monoclonal antibody and gemcitabine [G] combination in the Phase III setting in patients with advanced PC. Methods: Eligibility included locally advanced unresectable or metastatic PC; adequacy of organ function; performance status (PS) 0- 2; no prior EGFR therapy; no prior systemic chemotherapy except for adjuvant chemotherapy; and submission of tumor for EGFR immunostaining. The primary endpoint was overall survival. Secondary endpoints included objective response, time to progression, pain control, and quality of life. Assuming 6 months median survival, the study was designed to detect a median improvement to 8 months (1.33 hazard ratio) with 90% power, based on a one-sided 0.0125 test, and 704 eligible patients. Primary analyses used a Cox regression model, stratified for factors used in the randomization. Patients were stratified by PS, stageand prior pancreatectomy, and randomized to either G alone or G plus C. G was given at a dose of 1,000 mg/m2/wk for seven weeks out of 8, then 3 weeks on and one week off. C was given as a loading dose of 400 mg/m2 on week 1 and then 250 mg/m2 weekly. Results: 766 pts (735 eligible) with a median age of 64 (30–91) were enrolled by SWOG and CTSU between January 2004 and April 2006. Of those, 51% were males, 21.5% had locally advanced disease, and 13% had PS of 2. The study closed with full accrual. The median survival was 6 months in the G arm and 6.5 months in the G plus C arm for an overall HR of 1.09 (95% CI 0.93–1.27, p= 0.14) . The corresponding PFS was 3 months and 3.5 months, for G and G+C arms, respectively (HR =1.13, 95%CI .97–1.3, p=.058). The confirmed response probabilities were 7 % in each arm, and inclusion of unconfirmed responses yielded 14% in the G arm and 12% in the G + C arm.702 pts were evaluable for toxicity. 90 pts experienced at least one grade 4 toxicity; 14% on the G plus C, 11% on G alone. Conclusions: This study failed to demonstrate a clinically significant advantage of the addition of cetuximab to gemcitabine for overall survival, PFS and response in advanced PC. No significant financial relationships to disclose.

Prognostic factors for metastatic colorectal cancer with and without bevacizumab therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14163-e14163
Author(s):  
Ikenna Osuorji ◽  
Greg Dyson ◽  
Durga Yerasuri ◽  
Philip Agop Philip ◽  
Anthony Frank Shields ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Platelet Count ◽  
Regression Model ◽  
Median Survival ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Colorectal Disease ◽  
Cox Regression Model ◽  
Platelet Counts ◽  
The Impact

e14163 Background: Metastatic colorectal disease is generally incurable and treatment is palliative with the intent to balance toxicity with quality of life. Coin 3 trial showed that pre-chemotherapy platelet counts > 400,000 per μL were associated with poor survival when intermittent chemotherapy was used, whereas patients with lower platelet counts did not have any significant difference between the intermittent and continuous chemotherapy arms. Methods: We reviewed retrospectively 775 stage IV colorectal cancer patients at Karmanos Cancer Center over a 10 year period to see if high platelet count was associated with a poor outcome irrespective of treatment. Our analysis included 480 patients with adenocarcinoma who had not received chemotherapy prior to referral, and where information on the baseline platelet count, race, and age was available. We also analyzed the impact of race, age and bevacizumab use. We used Cox regression model for analysis. Results: Among the patients 48.3% were African American (AA) and 51.7% were Caucasians (C). 34.4 % had had PLT > 400,000 per μL. For those with lower platelet counts the median survival was 26.2 months in the C and 14.1 months in the AA groups respectively. Patients with platelet above 400,000 had a median survival of 15.2 months for C and 12.6 months for AA. Cox regression analysis, showed hazard ratios for outcome of death were; 1.16(1.07-1.26) p<0.001 for age (per 10 yrs), 1.60(1.31-1.94) [AA versus C(ref)] p< 0.001 for race and 1.35(1.10-1.65)[>400 versus <] p<0.004 for platelet count. In subset analysis, 296(61.7%) patients who received chemotherapy had data regarding use of bevacizumab (B). Among the 31.7% who received B, the median survival was 25.6 months compared to14.1 months in the no B arm. A Cox regression model using B as a stratification variable showed that the impact of race {hazard ratio = 1.32 (1.02-1.69) p =0.03} and platelet count {hazard ratio = 1.27(0.97-1.65) p =0.08} were much less. Conclusions: Pre-chemotherapy Platelet count< 400,000, C race and younger age are associated with improved survival. Use of bevacizumab may mitigate the impact of these factors.

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