Secondary resection in a general mCRC population with cetuximab-based first-line treatment: Interim analysis of the German noninterventional study ERBITAG.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14532-e14532
Author(s):  
Ulf P Neumann ◽  
Thomas Goehler ◽  
Gernot Reich ◽  
Michael Schwerdtfeger ◽  
Patrick Stuebs ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Response Rate ◽  
Performance Status ◽  
R0 Resection ◽  
Line Treatment ◽  
Resection Rate ◽  
First Line ◽  
Ecog Performance Status ◽  
Noninterventional Study ◽  
First Line Treatment

e14532 Background: Resection of liver and/or lung metastases (LM) are a potentially curative option for patients with mCRC. Cetuximab in combination with irinotecan- or oxaliplatin-based chemotherapy has shown to increase the resection rate of primarily unresectable LM in mCRC patients. After approval of cetuximab in Germany for first-line treatment of pts with unresectable mCRC, this noninterventional study was initiated to evaluate safety and efficacy of cetuximab in combination with various first-line chemotherapy regimens in patients with unresectable mCRC. Methods: We conducted an interim analysis of the first 124 fully documented pts to evaluate the response rate (RR) and resection rate of LM. Enrolment was restricted to pts with mCRC with proven KRAS wildtype mutation status without prior systemic treatment in the metastatic stage. Predefined endpoints were amongst others RR, LM resection rate, TTF, PFS, OS, and safety. Results: From May 2010 to May 2012 360 eligible pts were enrolled at 109 sites (75% office-based physicians), documentation for 124 was finalised (data cut-off for this analysis 03 May 2012) and evaluated. The median age was 68 [range 34-84] years, ECOG performance status was 0, 1, 2 in 29%, 60%, and 9% of pts, respectively, in 2% of pts ECOG performance status was missing. Resection rate was 18.5% (n=23) performed at 18 sites with 16.9% R0 resections (n=21). 42% of pts (n=52) had liver-limited disease (LLD). Resection rate in pts with LLD was 34.6% (n=18) with a 30.6% R0-resection rate (n=16). Median treatment duration from start of cetuximab-based therapy to resection of LM was 3.7 months [0.7-12.0]. Objective response rate was 46.8% (CR 4.8%, PR 41.9%) and 59.6% (CR 5.8%, PR 53.8%) for pts with LLD. Conclusions: In a clinical practice setting cetuximab-based first-line treatment of an unselected population with KRAS wildtype mCRC resulted in an R0-resection rate of 16.9% overall, and 30.6% for LLD pts. These data compare fairly well with data from clinical trials: CRYSTAL, OPUS, and CELIM.

Secondary resection in a general mCRC population with cetuximab-based first-line treatment: Interim analysis of the German noninterventional study ERBITAG.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 590-590 ◽  
Author(s):  
Friedrich Overkamp ◽  
Thomas Goehler ◽  
Gernot Reich ◽  
Michael Schwerdtfeger ◽  
Patrick Stuebs ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Response Rate ◽  
Performance Status ◽  
R0 Resection ◽  
Line Treatment ◽  
Resection Rate ◽  
First Line ◽  
Ecog Performance Status ◽  
Noninterventional Study ◽  
First Line Treatment

590 Background: Resection of liver and/or lung metastases (LM) are a potentially curative option for patients with mCRC. Cetuximab in combination with irinotecan- or oxaliplatin-based chemotherapy has shown to increase the resection rate of primarily unresectable LM in mCRC patients. After approval of cetuximab in Germany for first-line treatment of pts with unresectable mCRC, this noninterventional study was initiated to evaluate safety and efficacy of cetuximab in combination with various first-line chemotherapy regimens in patients with unresectable mCRC. Methods: We conducted an interim analysis of the first 124 fully documented pts to evaluate the response rate (RR) and resection rate of LM. Enrolment was restricted to pts with mCRC with proven KRAS wildtype mutation status without prior systemic treatment in the metastatic stage. Predefined endpoints were amongst others RR, LM resection rate, TTF, PFS, OS, and safety. Results: From May 2010 to May 2012 360 eligible pts were enrolled at 109 sites (75% office-based physicians), documentation for 124 was finalised (data cut-off for this analysis 03 May 2012) and evaluated. The median age was 68 [range 34-84] years, ECOG performance status was 0, 1, 2 in 29%, 60%, and 9% of pts, respectively, in 2% of pts ECOG performance status was missing. Resection rate was 18.5% (n=23) performed at 18 sites with 16.9% R0 resections (n=21). 42% of pts (n=52) had liver-limited disease (LLD). Resection rate in pts with LLD was 34.6% (n=18) with a 30.6% R0-resection rate (n=16). Median treatment duration from start of cetuximab-based therapy to resection of LM was 3.7 months [0.7-12.0]. Objective response rate was 46.8% (CR 4.8%, PR 41.9%) and 59.6% (CR 5.8%, PR 53.8%) for pts with LLD. Conclusions: In a clinical practice setting cetuximab-based first-line treatment of an unselected population with KRAS wildtype mCRC resulted in an R0-resection rate of 16.9% overall, and 30.6% for LLD pts. These data compare fairly well with data from clinical trials: CRYSTAL, OPUS, and CELIM.

Outcome of patients with KRAS exon 2 wildtype (KRAS-wt) metastatic colorectal carcinoma (mCRC) with cetuximab-based first-line treatment in the noninterventional study ERBITAG and impact of comorbidity and age.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 651-651 ◽  
Author(s):  
Stephan Sahm ◽  
Thomas Goehler ◽  
Christiane Hering-Schubert ◽  
Jan Janssen ◽  
Ulf Peter Neumann ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Performance Status ◽  
Line Treatment ◽  
Resection Rate ◽  
First Line ◽  
Ecog Performance Status ◽  
Exon 2 ◽  
Trial Outcomes ◽  
Noninterventional Study ◽  
First Line Treatment

651 Background: Cetuximab in combination with irinotecan- or oxaliplatin-based chemotherapy has shown to increase ORR, PFS, OS of KRAS-wt mCRC patients (pts). ERBITAG aimed to evaluate safety and efficacy of cetuximab in combination with various first-line chemotherapy regimens in pts with unresectable KRAS-wt mCRC. Methods: KRAS-wt pts on a cetuximab-based first-line treatment with written informed consent could be enrolled in this prospective, non-interventional study. Primary endpoint was ORR, secondary endpoints were amongst others PFS, OS, TTF, and resection rate of liver metastasis. Comorbidities were documented and evaluated by the Charlson Comorbidity Index (CCI). Results: 817 eligible KRAS-wt mCRC pts were enrolled at 144 sites across Germany, documentations for 456 pts were finalised and evaluated. The median age was 65 [27-87] yrs, with 51.5% ≤65 yrs, 34.0% >65-75 yrs, and 14.5% >75 yrs. ECOG performance status was 0, 1, 2, or missing in 34.4%, 49.6%, 8.8%, and 7.2% of pts, respectively. CCI was 0 in 54.4%, and ≥1 in 45.6%. Resection of liver and/or lung metastases was done in 17.3% of pts, 13.4% were R0 resected. For pts with liver limited disease resection rate and R0-rate were 29.3% and 23.8%, respectively. Pts with CCI 0 had no different outcome regardless of age (table). Pts with CCI ≥1 and >75 yrs had a lower ORR and decreased TTF, pts >65-75 yrs had only a decreased TTF as compared to the ≤ 65 yrs age group (table). Conclusions: In this large observational trial outcomes (ORR and PFS) of KRAS-wt mCRC pts on a cetuximab-based first-line treatment were comparable to those reported in pivotal trials. Pts older than 75 yrs without comorbidities (CCI =0) showed no difference to younger pts in ORR, PFS, and TTF. Pts >75 yrs with CCI ≥ 1 had a significant lower ORR and decreased TTF. Clinical trial information: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_455. [Table: see text]

Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
E. Van Cutsem ◽  
M. Nowacki ◽  
I. Lang ◽  
S. Cascinu ◽  
I. Shchepotin ◽  
...  
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Skin Reactions ◽  
Group A ◽  
Group B ◽  
First Line Treatment

4000 Background: Cetuximab in combination with irinotecan-based regimens has proven activity in previously-treated patients (pts) with mCRC. The present trial investigated the effectiveness of cetuximab in combination with standard FOLFIRI compared with FOLFIRI alone in the first-line treatment of pts with epidermal growth factor receptor (EGFR)-expressing mCRC. Methods: Pts were randomized 1:1 to receive either cetuximab (400 mg/m2 initial dose then 250 mg/m2/week [w]) plus FOLFIRI q 2 w (irinotecan 180 mg/m2, FA 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours) (Group A) or FOLFIRI alone (Group B). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate (RR), disease control rate and safety. 633 events were required to statistically differentiate PFS between groups with 80% power. Results: Between August 2004 and October 2005, 1,217 pts were randomized, 608 to Group A and 609 to Group B (60% male, median age 61 [19–84], ECOG performance status: 0=54%; 1=43.5%; 2=3.5%). Median PFS was significantly longer for Group A compared to Group B (8,9 months [8 - 9,5] for Group A vs. 8 months [7.6 - 9] for Group B, p=0.036). Response Rate was also significantly increased by cetuximab (46.9% vs. 38.7%, p=0.005). Treatment was generally well tolerated with neutropenia (26.7% Group A, 23.3% Group B), diarrhea (15.2% and 10.5% respectively) and skin reactions (18.7% and 0.2% respectively) being the most common grade 3/4 adverse events. Conclusions: Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone. [Table: see text]

A randomized, double-blinded, phase II study of paclitaxel/carboplatin (PC) plus CT-322 versus PC plus bevacizumab (Bev) as first-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7584-7584 ◽  
Author(s):  
Eugene Henry Paschold ◽  
Julien Mazieres ◽  
Hervé Lena ◽  
Giorgio Cruciani ◽  
Glen Laird ◽  
...  
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Randomized Study ◽  
Disease Stage ◽  
Line Treatment ◽  
First Line ◽  
Bleeding Events ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
First Line Treatment

7584 Background: CT- 322 is a pegylated protein engineered from the tenth type III human fibronectin domain thatspecifically blocks VEGFR-2 signaling by all known ligands. This international randomized study assessed the efficacy and safety of PC + CT-322 compared to PC + Bev as first-line treatment for advanced non-squamous NSCLC. Methods: In addition to paclitaxel 200 mg/m2and carboplatin AUC 6 given on day 1 of a 21 day cycle(maximum 6 cycles), subjects, stratified by ECOG performance status, disease stage, and site, were randomized 1:1 to receive either CT-322 2 mg/kg on days 1, 8, and 15 (arm A) or Bev 15 mg/kg on day 1 and placebo on days 8 and 15 (arm B). CT -322 and Bev/placebo were continued as maintenance until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety. Results: 255 subjects were randomized to arm A (n=127) or arm B (n=128). Baseline characteristics were wellbalanced. After a median follow- up of 13.8 months, 9 subjects on arm A and 24 on arm B remained on study treatment. The median treatment duration was 19 weeks in arm A and 26.3 weeks on arm B. The median PFS in arm A was 5.6 months compared to 6.8 months in arm B (HR 1.51, 1 -sided p=0.997). In all prespecified subgroups, PFS was favored in arm B. The response rate was 25.2% in arm A compared to 32.8% in arm B. Median OS was 12.5 months in arm A compared to 15.2 months in arm B. The most common grade ≥ 3 adverse events (Arm A vs B) were neutropenia (47.2% vs 49.2%), thrombocytopenia (11.8% vs 6.3%), and fatigue (10.2% in both arms). Grade ≥ 3 hypertension was more frequently reported in arm A (8.7% vs 3.1%). Grade ≥ 3 venous thrombosis (5.5% vs 6.3%), proteinuria (1.6% vs 2.3%), and bleeding events (0.8% vs 1.6%) were similar. Conclusions: PC + CT-322 failed to improve PFS, OS, or response rate compared to PC + Bev. However, thesafety profile in the PC + CT-322 arm was consistent with the anti-angiogenic mechanism of action, suggesting that CT-322 has biological activity as an inhibitor of VEGFR-2.

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 526-526 ◽  
Author(s):  
Barbara Eichhorst ◽  
Anna-Maria Fink ◽  
Raymonde Busch ◽  
Elisabeth Lange ◽  
Hubert Köppler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Interim Analysis ◽  
Research Funding ◽  
Response Rate ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Introduction FCR is the current standard first line treatment regimen in advanced CLL (Hallek et al., Lancet, 2010), but is associated with significant side effects. The GCCLSG initiated an international phase III study in order to test the non-inferiority regarding efficacy and potentially better tolerability of BR compared to FCR in first-line therapy of physically fit pts without del(17p). Methods and Patients 688 CLL pts from 158 sites in five countries (Germany, Austria, Switzerland, Denmark and Czech Republic) were screened centrally for immunophenotype, genomic aberrations by FISH, IGHV sequenzing, comorbidity burden and renal function. 564 CLL pts with CIRS score ≤ 6, creatinine clearance > 70 ml/min and without del(17p) were enrolled between October 2008 and June 2011. Pts were randomly assigned to receive 6 courses of either FCR (N= 284; F 25mg/m2 i.v. d1–3, C 250 mg/m2 i.v. d1–3, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days) or BR (N=280; B 90mg/m2 i.v. d1+2, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days). The intent-to-treat population consisted of 561 pts, because three patients were excluded due to deferred treatment (1 pt decision, 1 treatment before randomization, 1 misdiagnosis). 22 % were Binet A, 38 % Binet B and 40 % Binet C. The median age was 62 years (yrs) (range 33 to 82), median CIRS score 2 (range 0-6). There were significantly more pts with unmutated IGVH in the BR arm (68%) in comparison to the FCR arm (55%; p=0.003). All other characteristics including median age were well balanced. A mean number of 5.27 courses was given in the FCR arm versus 5.41 courses in the BR arm (p=0.022). 70.6% (FCR) and 80.3% (BR) of pts received 6 courses (p=0.008). Dose was reduced by more than 10% in 27.3% (FCR) and 31.6% (BR) of all courses given (p = 0.012). Results The median observation time was 27.9 months (mo) in all pts alive. While response evaluation was missing in 14 pts, 547 pts (274 FCR; BR 273) were evaluable for response and all 561 pts (282 FCR; 279 BR) for progression-free survival (PFS), event-free survival (EFS) and OS. The overall response rate was identical in both arms with 97.8% (p=1.0). The complete response rate (CRR) (confirmed by central immunhistology) with FCR was 47.4% as compared to 38.1% with BR (p=0.031). MRD data were available at interim analysis from 192 pts (99 FCR; 93 BR) of the first 300pts. 71.7% of pts in the FCR and 66.7% in the BR arms achieved MRD-levels below 10-4 in peripheral blood at final staging (p=0.448). The complete MRD data set will be available by November. PFS was 85.0% at 2 yrs in the FCR arm and 78.2% in the BR arm (p=0.041). EFS was 82.6% at 2 yrs in the FCR arm and 75.7% in the BR arm (p=0.037).There was no difference in OS rate for the FCR vs BR arm (94.2% vs 95.8% at 2 years p=0.593). Hazard Ratio for PFS, EFS and OS was 1.385, 1.375 and 0.842 respectively. PFS was assessed in pts < 65 yrs and ≥ 65 yrs. While there was a significant difference in pts < 65 yrs between both treatment arm (median PFS for BR 36.5 mo vs not reached for FCR; p=0.016), the difference disappeared in elderly pts (not reached vs. 45.6 mo; p=0.757). A multivariate analysis including treatment arm, Binet stage, age, sex, comorbidity, serum TK, serum beta2-microglobulin (Beta2M), del(11q) and IGHV status identified treatment arm, Beta2M, del(11q) and IGHV as independent prognostic factors for PFS and EFS. FCR treated pts had significantly more frequent severe, CTC grade 3 to 5, adverse events during the whole observation period (90.8% vs 78.5%; p<0.001). Especially severe hematotoxicity was more frequent in the FCR arm (90.0% vs 66.9%, p<0.001). The higher rate of severe neutropenia (81.7% vs 56.8%, p<0.001) resulted in a significantly higher rate of severe infections (39.0% vs 25.4%, p=0.001) in the FCR arm, especially in the elderly (FCR: 47.4% vs BR: 26.5%; p=0.002). Treatment related mortality occurred in 3.9% (n=11) in the FCR and 2.1% (n=6) in the BR arm. Conclusion The results of this planned interim analysis show that FCR seems more efficient than BR in the first-line treatment of fit CLL pts with regard to higher CRR, as well as longer PFS and EFS. These advantages might be balanced by a higher rate of severe adverse events, in particular neutropenia and infections, associated with FCR. In light of these results, no firm recommendation of one regimen over the other can be given at the present time regarding the first-line use in CLL pts with good physical fitness. Disclosures: Eichhorst: Roche: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding. Gregor:Roche: Consultancy, Honoraria, Travel Support Other; Mundipharma: Travel Support, Travel Support Other. Plesner:Mundipharma: Research Funding. Trneny:Roche: Honoraria, Research Funding. Fischer:Roche: Travel grants Other; Mundipharma: Travel grants, Travel grants Other. Kneba:Roche: Consultancy, Research Funding. Wendtner:Roche: Consultancy, Research Funding; Mundipharma: Consultancy, Research Funding. Kreuzer:Roche: Honoraria; Mundipharma: Honoraria. Stilgenbauer:Roche: Consultancy, Research Funding, Travel grants Other; Mundipharma: Consultancy, Research Funding. Böttcher:Roche: Honoraria, Research Funding. Hallek:Janssen: Research Funding; Gilead: Research Funding; Roche: Research Funding.

Final results of ECOG 3503: A pilot study to determine if downstream markers of EGFR linked signaling pathways predict response to erlotinib (OSI-774) in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7588-7588 ◽  
Author(s):  
J. Kolesar ◽  
J. Brahmer ◽  
J. Lee ◽  
P. Guaglianone ◽  
J. Patel ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Response Rate ◽  
Performance Status ◽  
Primary Objective ◽  
Prolonged Survival ◽  
Fish Analysis ◽  
Line Treatment ◽  
First Line ◽  
Predictors Of Response ◽  
First Line Treatment

7588 Background: Predictors of response and survival in patients (pts) who benefit from Erlotinib (Elb) remain controversial. The primary objective is to prospectively identify downstream markers of EGFR linked signaling pathways that are predictive of response. The secondary objectives are to estimate response rate (RR), disease control rate (dcr), time to progression (ttp), survival, and if a grade (gr) 2 rash is predictive of survival. Methods: Pts with advanced NSCLC (Stage IIIB with pleural effusion and IV, no prior systemic treatment, performance status 0–2, no symptomatic CNS metastasis, and adequate renal, hepatic and hematologic function) were accrued to this single arm study. Elb was taken orally once a day until disease progression or unacceptable toxicity. Starting at 150 mg per day, the dose was escalated by 25 mg once every 2 weeks until a gr 2 rash developed, other toxicities precluded escalation, or 250 mg dose reached. Paraffin- fixed tumor tissue was collected on pts for correlative studies including quantitative immunohistochemistry (IHC) for pMAPK. Results: Of 137 pts recruited, 118 were eligible and 57 pts had adequate tissue to do IHC. Dose escalation occurred in 60/118 pts, with 15 getting up to 250 mg. The RR, by RECIST criteria, was 7% (8/112, 1 CR) with dcr of 46% (51/112). Most pts went off trial because of progression of disease (69%). Median survival was 7.9 months (mo), and median ttp was 3.5 mo. Of the 134 pts evaluated for toxicity, 43 (32%), 66 (49%), and 13 (10%) had a gr 1, 2 and 3 rash respectively. pMAPK was not a predictor for response. Using a median score of 20 as the cutoff for pMAPK as positive or negative, negative pMAPK tended to have a longer survival (7.6 mo vs. 5.3 mo, p=0.051). A gr ≥ 2 rash trended towards an association with prolonged survival (12.6 mo vs. 6.4 mo, p=0.099). Conclusions: Elb used as first-line treatment in an unselected population has a response rate and survival similar to first-line chemotherapy. Negative pMAPK may predict for prolonged survival but does not predict response. EGFR mutation and FISH analysis will be available at the meeting. No significant financial relationships to disclose.

Prognostic impact of human epidermal growth factor-2 (HER2) status on overall survival (OS) of advanced gastric cancer (AGC) patients (pts) treated with standard chemotherapy without trastuzumab as a first-line treatment: A Japanese multicenter collaborative retrospective study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4075-4075
Author(s):  
Tomohiro Nishina ◽  
Nozomu Fuse ◽  
Takeshi Kuwata ◽  
Shigenori Kadowaki ◽  
Eiji Shinozaki ◽  
...  
Keyword(s):  
Performance Status ◽  
Gastroesophageal Junction ◽  
Her2 Status ◽  
Prognostic Impact ◽  
Line Treatment ◽  
First Line ◽  
Standard Chemotherapy ◽  
Ecog Performance Status ◽  
Significant Difference ◽  
First Line Treatment

4075 Background: The prognostic impact of HER2 status on OS of AGC pts treated with standard chemotherapy without trastuzumab for first-line treatment remains controversial. This study investigated whether HER2 status is an independent prognostic factor for AGC pts. Methods: Formalin-fixed paraffin-embedded tumor samples from 293 eligible pts were examined for HER2 by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Eligible criteria included: 1) histologically confirmed gastric or gastroesophageal junction adenocarcinoma, 2) unresectable or recurrent cancer, 3) treated with S-1 plus cisplatin as first-line chemotherapy, 4) age: ≥20, 5) ECOG performance status score: 0-2 and 6) with archived tumor sample. HER2+ was defined as IHC 3+ or IHC 2+/FISH+. Results: Of 293 pts, 43 (15%) were HER2+. Baseline pt characteristics between HER2+ and HER2- pts were significantly different by histology (intestinal/diffuse, 65%/35% vs. 39%/61%; p=0.001), measurable disease by RECIST v1.0 (91% vs. 69%; p=0.003), No. of metastatic sites (≥2, 72% vs. 46%; p=0.003) and presence of liver metastasis (56% vs. 31%; p=0.003). After median follow-up time of 48.9 months with 270 (92%) death events, there was no significant difference in OS between HER2+ and HER2- pts (median, 11.7 vs. 13.7 months; hazard ratio [HR] 1.11, 95% CI 0.79–1.55; log rank p=0.550). After adjusting other prognostic factors with Cox hazard model, HER2+ was still not prognostic for OS (HR 0.890, 95% CI 0.627–1.262, p=0.513). Conclusions: HER2 status has no significant prognostic impact on OS of AGC pts treated with S-1 plus cisplatin without trastuzumab as a first-line treatment.

Is FOLFOXIRI alone or combined with targeted therapy administered as first-line treatment a reasonable choice for most patients with mCRC? Systematic review and network meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15018-e15018
Author(s):  
Mingyi Zhou ◽  
Ping Yu ◽  
Dengue Hernick ◽  
Yanrong Li ◽  
Yuanhe Wang ◽  
...  
Keyword(s):  
Target Therapy ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cochrane Collaboration ◽  
R0 Resection ◽  
Line Treatment ◽  
Resection Rate ◽  
First Line ◽  
First Line Treatment

e15018 Background: Controversy surrounds the question of whether the prognosis of most patients with metastatic colorectal cancer (mCRC) is improved using intensive administration of folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) alone or combined with target therapy as first-line treatment. Methods: We queried PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, ClinicalTrials.gov, the databases of the European Society for Medical Oncology and the American Society of Clinical Oncology to identify abstracts of randomized controlled trials evaluating the efficacies and toxicities of intensive therapies used for first-line treatment of patients with mCRC. The search included articles dated from the inception of these resources until December 31, 2016. We estimated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risks (RRs) for the objective response rate (ORR), the R0 resection rate, and toxicities. Results: Nine RCTs comprising 2,256 patients were included in this network meta-analysis. The PFS of patients administered FOLFOXIRI plus target therapy experienced prolonged PFS and OS and improved ORRs compared with FOLFOX or FOLFIRI plus target therapy (PFS: HR 0.65, 95% CI 0.46–0.91; OS: HR 0.80, 95% CI 0.65–0.98; ORR: HR 1.70, 95% CI 1.16–2.49; R0 resection rate: HR 2.66, 95% CI 1.86–3.82). There were no significant differences between PFS, OS, ORRs, or R0 resection rates and toxicities of patients administered FOLFOXIRI and FOLFOX or FOLFIRI plus target therapy. Further, FOLFOXIRI plus target therapy did not increase toxicities compared with FOLFOX or FOLFIRI plus target therapy, except for neutropenia. Conclusions: FOLFOXIRI plus target therapy when administered as first-line treatment of patients with mCRC is the best choice and did not significantly increase toxicities. FOLFOXIRI is as effective as FOLFOX or FOLFIRI plus target therapy.

Phase II study of infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4089-4089 ◽  
Author(s):  
S. Kopetz ◽  
K. Y. Glover ◽  
C. Eng ◽  
R. A. Wolff ◽  
D. Z. Chang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Intention To Treat ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
First Line Treatment

4089 Background: When compared to bolus 5-fluorouracil (F), leucovorin (L), and irinotecan (I) regimens such as IFL, the infusional F, L, I regimen (FOLFIRI) resulted in a improved toxicity profile with a response rate (RR) of 35% and median progression free survival (PFS) of 6.7 months. When combined with bevacizumab (B) as first-line treatment, IFL demonstrated improved activity with a RR of 45% and a median PFS of 10.6 months. Combining FOLFIRI and B may further improve the efficacy. Methods: We designed a single-arm, phase II trial of FOLFIRI+B with B (5mg/kg), I (180mg/m2), bolus of F (400mg/m2) and L (400mg/m2) with a 46-hour infusion of F (2400mg/m2) every 2 weeks. The primary endpoint was PFS. Chemotherapy naïve mCRC patients (pts) with a performance status of 0–2 received B alone on Day -14, starting FOLFIRI+B on Day 1. Proteomic and radiographic correlative studies were completed and will be reported separately. Results: N=41 pts, median age 56 y/o (range 26–78), M:F = 16:25, 5 pts with prior adjuvant therapy, were enrolled from 1/2005 to 1/2007. A total of 502 cycles have been administered (median = 12). The median PFS is 12.6 months. Response rate by intention-to-treat analysis was 62% (24 pts), with 33% stable disease (13 pts). Responses occurred after a median of 4 months of therapy. Fifteen pts remain on treatment; 26 pts are off study: 7 for progressive disease, 2 withdrew consent, 7 for toxicity and 2 for surgery unrelated to cancer. Eight pts were removed from the study for metastasectomies. Grade 3 or 4 toxicities included 17 occurrences of grade = 3 neutropenia, including 1 grade 4 febrile neutropenia, 4 grade 4 pulmonary emboli, 2 grade 3 hand-foot syndrome, and 1 grade 3 diarrhea. One pt included in the analysis developed a possible microperforation, manifested by peritonitis, after B alone and never received FOLFIRI. Conclusion: FOLFIRI+B is well-tolerated and efficacious, with an impressive PFS that compares favorably to historical controls. This regimen is an excellent choice as a first-line treatment for mCRC. No significant financial relationships to disclose.

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