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.

scholarly journals Real World Treatment Patterns and Toxicity Among Elderly Patients with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5571-5571
Author(s):  
Jesus D Gonzalez-Lugo ◽  
Ana Acuna-Villaorduna ◽  
Joshua Heisler ◽  
Niyati Goradia ◽  
Daniel Cole ◽  
...  
Keyword(s):  
Side Effects ◽  
Real World ◽  
Research Funding ◽  
Treatment Patterns ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Treatment Change ◽  
Free Survival ◽  
First Line Treatment

Introduction: Multiple Myeloma (MM) is a disease of the elderly; with approximately two-thirds of cases diagnosed at ages older than 65 years. However, this population has been underrepresented in clinical trials. Hence, there are no evidence-based guidelines to select the most appropriate treatment that would balance effectiveness against risk for side effects in the real world. Currently, guidelines advise that doublet regimens should be considered for frail, elderly patients; but more detailed recommendations are lacking. This study aims to describe treatment patterns in older patients with MM and compare treatment response and side effects between doublet and triplet regimens. Methods: Patients diagnosed with MM at 70 years or older and treated at Montefiore Medical Center between 2000 and 2017 were identified using Clinical Looking Glass, an institutional software tool. Recipients of autologous stem cell transplant were excluded. We collected demographic data and calculated comorbidity burden based on the age-adjusted Charlson Comorbidity Index (CCI). Laboratory parameters included cell blood counts, renal function, serum-protein electrophoresis and free kappa/lambda ratio pre and post first-line treatment. Treatment was categorized into doublet [bortezomib/dexamethasone (VD) and lenalidomide/dexamethasone (RD)] or triplet regimens [lenalidomide/bortezomib/dexamethasone (RVD) and cyclophosphamide/bortezomib/dexamethasone (CyborD)]. Disease response was reported as VGPR, PR, SD or PD using pre-established criteria. Side effects included cytopenias, diarrhea, thrombosis and peripheral neuropathy. Clinical and laboratory data were obtained by manual chart review. Event-free survival was defined as time to treatment change, death or disease progression. Data were analyzed by treatment group using Stata 14.1 Results: A total of 97 patients were included, of whom 46 (47.4%) were males, 47 (48.5%) were Non-Hispanic Black and 23 (23.7%) were Hispanic. Median age at diagnosis was 77 years (range: 70-90). Median baseline hemoglobin was 9.4 (8.5-10.5) and 14 (16.1%) had grade 3/4 anemia. Baseline thrombocytopenia and neutropenia of any grade were less common (18.4% and 17.7%, respectively) and 11 patients (20%) had GFR ≤30. Treatment regimens included VD (51, 52.6%), CyborD (18, 18.6%), RD (15, 15.5%) and RVD (13, 13.4%). Overall, doublets were more commonly used than triplets (66, 68% vs 31, 32%). Baseline characteristics were similar among treatment regimen groups. There was no difference in treatment selection among patients with baseline anemia or baseline neutropenia; however, doublets were preferred for those with underlying thrombocytopenia compared to triplets (93.8% vs 6.2%, p<0.01). Median first-line treatment duration was 4.1 months and did not differ among treatment groups (3.9 vs. 4.3 months; p=0.88 for doublets and triplets, respectively). At least a partial response was achieved in 47 cases (63.5%) and it did not differ between doublets and triplets (61.7% vs 66.7%). In general, first line treatment was changed in 50 (51.5%) patients and the change frequency was higher for triplets than doublets (71% vs 42.4%, p<0.01). Among patients that changed treatment, 17(34.7%) switched from a doublet to a triplet; 15 (30.6%) from a triplet to a doublet and 17 (34.7%) changed the regimen remaining as doublet or triplet, respectively. There was no difference in frequency of cytopenias, diarrhea, thrombosis or peripheral neuropathy among groups. Median event-free survival was longer in patients receiving doublet vs. triplet therapy, although the difference was not statistically significant (7.3 vs 4.3 months; p=0.06). Conclusions: We show a real-world experience of an inner city, elderly MM cohort, ineligible for autologous transplantation. A doublet combination and specifically the VD regimen was the treatment of choice in the majority of cases. In this cohort, triplet regimens did not show better response rates and led to treatment change more often than doublets. Among patients requiring treatment, approximately a third switched from doublet to triplet or viceversa which suggest that current evaluation of patient frailty at diagnosis is suboptimal. Despite similar frequency of side effects among groups, there was a trend towards longer event-free survival in patients receiving doublets. Larger retrospective studies are needed to confirm these results. Disclosures Verma: Janssen: Research Funding; BMS: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

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.

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]

Effect of the addition of bevacizumab to first-line FOLFOX on efficacy, including response rate, progression-free survival, and overall survival, in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 588-588
Author(s):  
M. Suenaga ◽  
N. Mizunuma ◽  
S. Matsusaka ◽  
E. Shinozaki ◽  
M. Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

588 Background: Bevacizumab (BV) is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Used in combination with chemotherapy, BV has been shown to improve survival in both first- and second-line treatment for metastatic colorectal cancer (mCRC). However, it was reported that addition of BV to FOLFOX conferred only little survival benefit (Saltz et al. JCO2008). The aim of this study was to assess the efficacy of addition of BV to FOLFOX in first-line treatment for patients with mCRC. Methods: Bevacizumab was approved for mCRC in July 2007 in Japan. This study was conducted at a single institution and comprised 217 consecutive patients receiving first-line treatment for mCRC between 2005 and 2009. The primary objective was to compare survival benefit in patients treated with FOLFOX4 (FF) between 2005 and 2007 with that in patients receiving FOLFOX4+BV 5 mg/kg (FF+BV) between 2007 and 2009. Results: Total number of patients in the FF and FF+BV groups was 132 and 85, respectively. Characteristics of patients were as follows (FF vs. FF+B): median age, 62 yrs (range 28-76 yrs) vs. 60 yrs (range16-74 yrs); ECOG PS0, 98.8% vs. 81.8%; and median follow-up time, 20.8 months vs. 24.4 months. Median progression-free survival (PFS) in the FF and FF+BV groups was 10 months (95% CI, 8.7-11.3) and 17 months (95% CI, 10.2-14.1), while median overall survival (OS) was 21 months (95% CI, 17.9-24.1) and not reached, respectively. Response rate was 46% (95% CI, 37- 54) in FF, and 62% (95% CI, 51-73) in FF+BV. Addition of BV to FOLFOX4 significantly improved PFS (p=0.002) and OS (p<0.001). Conclusions: The additive effect of BV for first-line FOLFOX was reconfirmed. These data indicate potential survival benefits from the addition of BV to FOLFOX in first-line treatment of mCRC. In addition, PFS may be a sensitive indicator of outcome prior to post-treatment. No significant financial relationships to disclose.

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.

scholarly journals The Combination of Bortezomib with Cyclophosphamide, Epirubicin, Etoposide and Prednisone (BCHEP) Regimen As First-Line Treatment for Untreated Patients with Peripheral T Cell Lymphoma: A Prospective, Single Arm, Phase II Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2482-2482
Author(s):  
Haiyan Yang ◽  
Cong Li
Keyword(s):  
T Cell ◽  
Interim Analysis ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
First Line ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
First Line Treatment

Abstract Background: Peripheral T-cell lymphoma (PTCL) is a clinically and biologically heterogeneous disease with poor prognosis. The response rate of standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) is only 50-60%, with a poor long-term survival rate of 10-30%. The addition of etoposide to CHOP increases response rate, but not progression free survival (PFS) or overall survival (OS). Recent study reported that nuclear factor kappa B (NF-κB) pathway plays a critical role in PTCL. Bortezomib, a potent and reversible proteasome inhibitor, can induce tumor cell apoptosis by inhibiting activation of NF-κB pathway and has been recommended as single agent option in relapse/refractory PTCL. We aimed to study the efficacy and safety of bortezomib in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BCHEP) in newly diagnosed PTCL patients for the first time. METHODS: A prospective, single arm, phase 2 study was conducted (NCT04061772). This is an interim analysis. Patients with newly diagnosis of PTCL were treated with up to 6 cycles of BCHEP regimen every 3 weeks. Bortezomib was subcutaneously administered on Days 1 and 8 at a dose of 1.3 mg/m 2 in combination with CHEP， consisting of 100 mg/m 2 etoposide on Days 1 to 3, 750mg/m 2 cyclophosphamide on Day 1, 75mg/m 2 epirubicin on Day 1 and 100mg prednisone on Days 1 to 5. The primary endpoint of the study was ORR including complete response (CR) and partial response (PR). The secondary endpoints included progression free survival (PFS), overall survival (OS) and adverse events (AEs). RESULTS: Between February 2019 and January 2021, a total of twenty-six patients were enrolled. Median age was 57 years (range 37-69) and six (23.1%) were female. Pathological subtypes included ALK-positive anaplastic cell lymphoma (ALCL, n=2), ALK-negative ALCL (n=4), PTCL, not otherwise specified (PTCL-NOS, n=9) and angioimmunoblastic T-cell lymphoma (AITL, n=11). Nineteen patients had stage III/IV disease and eleven had B symptoms, including weight loss in three cases and fever in eight. Ten patients had elevated serum lactate dehydrogenase (LDH), eleven had IPI score higher than 2. All patients had completed BCHEP treatment for at least two cycles and received imaging evaluation. Ten patients received prophylaxis of intrathecal chemotherapy with methotrexate at least once. Three patients received consolidated radiotherapy for metabolic residuals after chemotherapy, while one received autologous hematopoietic stem cell transplantation as consolidation treatment. This study had reached the primary end point at this interim analysis. The ORR was 92.3% (24/26) with a CR rate of 57.7% (15/26). Two patients had progression of disease within two cycles of chemotherapy. After a median follow-up of 16.3 months, twelve patients had disease progression, and six died. Median PFS was 10.9 months and 1-year PFS rate was 65.4%. Median OS was 14.6 months and 1-year OS rate was 88.5%. No patient presented with Grade 5 AE. The most frequent all-grade hematological toxicity was leucopenia (42.3%,11/26), anemia (50%,13/26) and thrombocytopenia (23.1%, 6/26). Other common toxicity included intestinal infection or pneumonia (19.2%, 5/26), Grade 1 peripheral neuropathy (15.4%, 4/26) and nausea (7.7%, 2/26). Dose reduction was performed in eight patients. CONCLUSIONS: Interim results showed that bortezomib in combination with CHEP is associated with high response rate and manageable toxicity in patients with previously untreated PTCL. The BCHEP regimen may serve as a novel first-line treatment option for patients with PTCL. The study is going on to enroll patients and updating results, including the prognostic value of serum inflammatory factors. Larger trials will be necessary to further verify the efficacy of this regimen in treatment naïve PTCL patients and to overcome relapse after remission. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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