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.

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 (3_suppl) ◽  
pp. 70-70
Author(s):  
Jin Yan ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Yunwei Han ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Performance Status ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Multicenter Phase ◽  
First Line Treatment

70 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is considered as the standard first-line therapy for metastatic colorectal cancer (mCRC), and maintenance treatment is proven to be a promising and controversial therapeutic strategy which is mainly involved bevacizumab or capecitabine. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib is a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously. Previous studies indicated that anlotinib demonstrated clinical benefits for patients with mCRC. This study aimed to evaluate the efficacy and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib maintenance therapy for mCRC. Methods: ALTER-C-001 trial was an open label, single-arm, multicenter phase II study. A calculated sample size of 53 patients with previously untreated mCRC, ranging from 18-75 years old and an ECOG performance status ≤ 1 were planned to recruit. Eligible patients were treated with capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 6 cycles followed by maintenance therapy of anlotinib (12mg, po, d1~14, q3w) until disease progression or intolerable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints were ORR, DCR, DOR and safety. Results: From January 2020 to September 2020, a total of 9 patients were enrolled, 6 patients were available for efficacy assessment. In best overall response assessment (all confirmed), there were 66.7% PR (4/6), 16.7% SD (1/6) and 16.7% PD (1/6). The preliminary ORR and DCR of the 6 patients was 66.7% (95% CI, 22.3-95.7%) and 83.3% (95% CI, 35.9-99.6%), respectively. The median PFS was not reached. Most treatment-related adverse events (TRAEs) were grade 1-2. Grade 3 or above TRAEs were as follows: hypertriglyceridemia (33.3%), hypertension (16.7%), neutropenia (16.7%) and lipase elevated (16.7%). No grade 5 AEs were observed. Conclusions: The preliminary results indicated that anlotinib plus XELOX regimen followed by anlotinib monotherapy as first-line treatment exhibited antitumor efficacy and manageable toxicity for patients with mCRC. The study is still ongoing and the data will be updated subsequently. Clinical trial information: ChiCTR1900028417.

Phase III trial of a 3-weekly versus 5-weekly schedule of S-1 plus cisplatin (SP) combination chemotherapy for first-line treatment of advanced gastric cancer (AGC): SOS study.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA4024-LBA4024 ◽  
Author(s):  
Min-Hee Ryu ◽  
Eishi Baba ◽  
Kyung Hee Lee ◽  
Narikazu Boku ◽  
Young Iee Park ◽  
...  
Keyword(s):  
Performance Status ◽  
Gastroesophageal Junction ◽  
Dose Intensity ◽  
Phase Iii ◽  
Weekly Schedule ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
First Line Treatment

LBA4024 Background: 5-weekly S-1 plus cisplatin (SP5: S-1 80-120 mg/body/day on D1-21, cisplatin 60 mg/m2 on D8, every 5 weeks) has become a standard first-line chemotherapy for AGC in Japan based on the SPIRITS trial (Lancet Oncol. 2008;9:215). To strengthen the low-dose intensity of cisplatin in this SP5 for greater efficacy, a 3-weekly S-1 plus cisplatin (SP3: S-1 80 mg/m2/day on D1-14, cisplatin 60 mg/m2on D1, every 3 weeks) has been developed in Korea (Cancer Chemother Pharmacol. 2008;61:837). Methods: This SOS study was a multicenter, randomized, open-label, phase III study to evaluate whether SP3 was non-inferior/superior to SP5 in terms of progression-free survival (PFS) determined by a blinded central radiology review according to RECIST v1.1. Patients (pts) with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma and with no prior chemotherapy were randomized 1:1 to receive either SP3 or SP5 until disease progression or unacceptable toxicities. Results: Between February 2009 and January 2012, a total of 625 pts were randomized from 42 sites in Korea and Japan. Median age was 59.6 years. 99% of pts had ECOG performance status 0-1. 16% of pts had prior gastrectomy. 62% of pts had measurable lesions. With a median follow-up of 34.7 months (range, 14.2-48.8) in surviving pts, SP3 was significantly noninferior and superior to SP5 in PFS (median 5.5 months vs. 4.9 months; HR 0.82, 95% CI 0.68-0.99, p=0.0418). Overall response rate (ORR) was also better with SP3 than with SP5 (60% vs. 50%, p=0.029). However, OS of both groups was equivalent (median 14.1 vs. 13.9 months; HR 0.99, 95% CI 0.81-1.21, p=0.9068). Treatment was well tolerated in both arms, while SP3 was associated with more frequent G3/4 anemia (19% vs. 9%) and neutropenia (39% vs. 9%). Dose intensity was higher in SP3 than in SP5 for both agents (median 331 vs. 317 mg/m2/week for S-1, p<0.001; median 18 vs. 12 mg/m2/week for cisplatin, p<0.001). Conclusions: SP3 was noninferior and superior to SP5 in terms of PFS and ORR. However, considering the small benefit in PFS and no difference in OS, both SP3 and SP5 can be recommended for the first-line treatment of AGC. Clinical trial information: NCT00915382.

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]

Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomized phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4035-4035 ◽  
Author(s):  
C. Bokemeyer ◽  
I. Bondarenko ◽  
A. Makhson ◽  
J. T. Hartmann ◽  
J. Aparicio ◽  
...  
Keyword(s):  
Adverse Events ◽  
Performance Status ◽  
Controlled Study ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Curative Intent ◽  
Grade 3 ◽  
Ecog Ps ◽  
First Line Treatment

4035 Background: FOLFOX-4 is a standard first-line treatment for patients (pts) with mCRC. The IgG1 monoclonal antibody cetuximab has proven activity in combination with cytotoxic chemotherapy. Excellent response rates (RRs) have been reported with first-line cetuximab and FOLFOX-4. This randomized, controlled study was conducted to compare RRs of FOLFOX-4 + cetuximab vs FOLFOX-4. Methods: Pts with previously untreated epidermal growth factor receptor (EGFR)-expressing mCRC not resectable with curative intent were eligible. They were randomized 1:1, stratified by ECOG performance status (PS) (0–1 vs 2), to either Group A (cetuximab 400 mg/m2 initial dose then 250 mg/m2/week plus FOLFOX-4 every 2 weeks [oxaliplatin 85 mg/m2 day (d) 1; FA 200 mg/m2 d1, 2; 5-FU 400 mg/m2 bolus + 600 mg/m2 infusion over 22 h, d1, 2]) or Group B (FOLFOX-4 only). The primary objective was the best confirmed RR assessed by independent review; secondary objectives were progression- free survival (PFS), overall survival (OS), the R0 resection rate after metastatic surgery of curative intent and safety. Results: Between July 2005 and March 2006, 337 pts were randomized and treated in more than 70 centers in Europe. 181 (53.7%) pts were male; the median age of all pts was 61.0 years [24–82]; 305 (90.5%) pts had an ECOG PS of 0 or 1, and 32 (9.5%) of 2. The best overall confirmed RR was 45.6% in A and 35.7% in B. For pts with ECOG PS 0–1, RR was 49.0% in A and 36.8% in B (Odds Ratio 1.648, 95%CI [1.043- 2.604]). PFS and OS results are not yet available. The most common grade 3/4 adverse events were neutropenia (27.6% in A; 31.5% in B), diarrhea (7.1 and 6.0%), leucopenia (7.1 and 5.4%) and rash (9.4%, in A only). Conclusions: The addition of cetuximab increased the RR of FOLFOX-4 in first-line treatment of mCRC. Grade 3/4 adverse events, with the exception of skin rash, were not significantly more frequent in the cetuximab arm. No significant financial relationships to disclose.

Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer (mCRC): Final analysis—Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 460-460
Author(s):  
Satoshi Yuki ◽  
Yoshito Komatsu ◽  
Hiraku Fukushima ◽  
Takahide Sasaki ◽  
Toraji Amano ◽  
...  
Keyword(s):  
Adverse Events ◽  
Primary Endpoint ◽  
Performance Status ◽  
Rest Period ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
First Line Treatment

460 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of Irinotecan plus S-1 (IRIS) to FOLFIRI for mCRC, with progression-free survival (PFS) as the primary endpoint. We previously reported that IRIS plus bevacizumab (IRIS/Bev) is very effective as first-line treatment (Komatsu Y et al. Acta Oncol. 2012 May 4). We now report the final results of this study. Methods: Eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, ECOG performance status (PS) of 0-1, and no history of prior chemotherapy. S-1 (40-60 mg depending on patients body surface area) was given orally, twice daily for 2 consecutive weeks, and 100 mg/m2irinotecan and 5 mg/kg bevacizumab was given intravenously on day 1 and 15, followed by 2-week rest period, within a 4-week cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), PFS, and overall survival (OS). Results: A total of 53 patients were enrolled from October 2007 through March 2009. The results were reported for 52 patients with evaluable lesions. The clinical characteristics of the patients were as follows. The median age was 63.5 years (range, 48 to 82). The male:female ratio was 3:2. The most common grade 3 or 4 adverse events were neutropenia (27%) and diarrhea (17%). Grade 3 or 4 hypertension (21%) was attributed to bevacizumab, but there were no life-threatening adverse events, such as gastrointestinal perforation. On an intention-to-treat basis, OR was 63.5% [95% confidence interval (CI) 50.4-76.5%], and the disease control rate was 94.2%. With a median follow-up time of 51.7 months, median PFS was 17.0 months (95%C.I. 14.2-19.8 months) and median survival time was 39.6 months (95%C.I. 34.2-45.0 months). Conclusions: IRIS/Bev is a remarkably active and generally well-tolerated first-line treatment for patients with mCRC. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab: TRICOLORE study) is already started. Clinical trial information: NCT00569790.

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