Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 561-561
Author(s):  
S. Yuki ◽  
K. Shitara ◽  
M. Yoshida ◽  
D. Takahari ◽  
S. Utsunomiya ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Standard Regimen ◽  
Free Survival

561 Background: Weekly cetuximab and irinotecan is a standard regimen in heavily pretreated patients with metastatic colorectal cancer (MCRC). The aim of this study was to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pretreated MCRC harboring wild-type KRAS. Methods: Patients with wild- type KRAS MCRC that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included in this study. Cetuximab was administered at 500 mg/m2 biweekly with irinotecan. The primary endpoint was response rate. The secondary endpoints included adverse events, progression-free survival, and overall survival. The pharmacokinetics of cetuximab was also evaluated in five patients. Results: From May, 2009 to February, 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 assessable patients, ECOG PS was 0 in 12, 1 in 16, and 2 in two patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4), and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95%CI, 61.4-92.3). The median progression-free survival was 5.3 months (95%CI, 3.4-7.3). Grade 3 skin toxicity was observed in 3 patients (10%), and treatment related death due to pneumonia occurred in one patient. Conclusions: The efficacy data are similar to those of standard dose of cetuximab plus irinotecan. Combination chemotherapy with biweekly cetuximab and irinotecan is effective for pretreated metastatic wild-type KRAS MCRC. No significant financial relationships to disclose.

A phase II trial of panitumumab with irinotecan and S-1 (IRIS) as second-line treatment in patients with wild-type KRAS metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 732-732
Author(s):  
Rai Shimoyama ◽  
Tetsuo Kimura ◽  
Toshi Takaoka ◽  
Kazuki Sakamoto ◽  
Shunji Kawamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Second Line ◽  
Wild Type ◽  
Free Survival ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

732 Background: Panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in second-line chemotherapy increased objective response rate and prolonged progression-free survival (PFS) versus FOLFIRI alone in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) (Peeters et al, J Clin Oncol 2010). This trial (UMIN000004659) evaluated tolerability and efficacy of combination therapy with irinotecan and S-1, an oral fluoropyrimidine (IRIS) plus panitumumab as second-line chemotherapy in patients with WT KRASmCRC. Methods: Main inclusion criteria were: patients with WT KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/m2) and irinotecan (100 mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was completion rate of protocol therapy (CRT). The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Thirty-seven patients were enrolled in 9 centers. The overall CRT was 62.2% (23/37). Most frequent grade 3/4 toxicities were: skin rash (24%), diarrhea (16%), and appetite loss (11%). The overall RR was 32.4% (12/37). Of these, four patients underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI: 3.5-15.4 months) and 20.1 months (95% CI: 16.7-23.2 months), respectively. Conclusions: IRIS plus panitumumab has acceptable toxicity profile and promising efficacy in patients with previously treated WT KRAS mCRC. This regimen can be an additional treatment option for second-line chemotherapy in WT KRAS mCRC. Clinical trial information: UMIN000004659.

Cetuximab Plus Various Chemotherapy Regimens for Patients with KRAS Wild-Type Metastatic Colorectal Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Payam Azadeh ◽  
Nafiseh Mortazavi ◽  
Arezoo Tahmasebi ◽  
Farnaz Hosseini Kamal ◽  
Kambiz Novin
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
The Other ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Standard Chemotherapy ◽  
Free Survival

Background: The aim of this study was to compare the efficacy and hematologic toxicity of cetuximab combined with various types of chemotherapy regimens in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Methods: The response rate, progression-free survival (PFS) and overall survival of the patients were analyzed. Results: In total, 45 patients were included in the study. The overall response rate for the combination of cetuximab and FOLFOX, FOLFIRI and CAPOX was 20, 46 and 30%, respectively, but the differences were not statistically significant. The median PFS for the three groups were 8, 6 and 3.5 months, respectively, but again these differences were not significant. All-grade leukopenia and anemia for the cetuximab plus FOLFOX group were significantly higher than for the other chemotherapy regimens. Conclusion: Our findings suggest that the combination of cetuximab and the three standard chemotherapy regimens resulted in the same outcomes in our patient population of mCRC, with higher hematologic toxicities among the FOLFOX subgroup.

Apatinib monotherapy for chemotherapy-refractory metastatic colorectal cancer: A multicenter, single-arm, prospective study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3527-3527 ◽  
Author(s):  
Fen Wang ◽  
Shubin Wang ◽  
Xia Yuan ◽  
Jun Jia ◽  
Xiaoxia Bi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prospective Study ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Free Survival

3527 Background: Apatinib is an oral highly-selective tyrosine kinase inhibitor (TKI) that blocks vascular endothelial growth factor receptor 2 (VEGFR-2). This exploratory study evaluated the efficacy and safety of apatinib monotherapy in patients with chemotherapy-refractory metastatic colorectal cancer. Methods: In this multicenter, single-arm, prospective study, 48 patients with metastatic colorectal cancer who had failed at least two lines standard chemotherapies including fluorouracil, oxaliplatin and irinotecan were recruited from 14 centers in Guangdong, China. Apatinib at a 500mg dose was administered daily continuously. Each cycle was 4 weeks (28 days). The primary endpoint was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. Results: A total of 48 patients was enrolled in the study from September 3, 2015 to June9, 2017. Four patients achieved a partial response, and 22 achieved stable disease, representing a response rate of 8.3% and a disease control rate of 60.4%. Median follow-up time was 10.3 months. Median progression-free survival (PFS) and overall survival (OS) of evaluable patients (n=41) were 4.7 months (95% confidence interval [CI] 3.7-5.9) and 9.7 months (95% CI 5.9-13.6). The most common grade 3 or 4 adverse events (AE) were hypertension (12.5%), hand-foot syndrome (10.4%), thrombocytopenia (10.4%), proteinuria (8.3%) and mucositis oral (6.3%). Conclusions: Apatinib monotherapy shows promising efficacy and manageable toxicities in patients with chemotherapy-refractory metastatic colorectal cancer. Further phase 3 trial is warranted. Clinical trial information: ChiCTR1900020503.

Panitumumab or cetuximab combined with irinotecan in patients with KRAS wild-type metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 642-642
Author(s):  
Nobuaki Ikezawa ◽  
Satoru Iwasa ◽  
Hirokazu Shoji ◽  
Yoshitaka Honma ◽  
Atsuo Takashima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Group Versus ◽  
Progression Free Survival ◽  
Similar Response ◽  
Wild Type ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

642 Background: Panitumumab and cetuximab are known to be effective in KRAS wild-type metastatic colorectal cancer (mCRC). However, it is not clear whether panitumumab and irinotecan confers benefit that are comparable to those of cetuximab and irinotecan in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes. Methods: We analyzed 139 patients who had received panitumumab or cetuximabu combined with irinotecan for KRAS wild-type mCRC previously treated with fluor opyrimidine-, oxaliplatin-, and irinotecan-based regimes.We evaluated and compared efficacy and safety of panitumumab plus irinotecan and cetuximab plus irinotecan. Results: Baseline characteristics were similar for the two groups receving cetuximab pulus irinotecan (n = 97) and panitumumab plus irinotecan (n = 42),respectively.In patients with measurable lesions,the response rate (unconfirmed complete or partial response) were 20% (18/92) in the group receving cetuximab plus irintecan and 34% (14/41) in that receving panitumumab plus irinotecan. Median progression-free survival was 5.7 months in the cetuximab plus irinotecan group versus 4.3 months in the panitumumab plus irinotecan group. Median overall survival was 11.2 months in the cetuximab plus irinotecan group versus 13.6 months in the panitumumab plus irinotecan group. The most common adverse events in the cetuximab plus irinotecan versus panitumumab plus irinotecan groups were all-grade rash acneiform (82% versus 90%), paronychia (61% versus 52%), and grade 3-4 neutropenia (26% versus 19%). Conclusions: Panitumumab or cetuximab plus irinotecan were well tolerated and produced similar response rate and survivals compared to those previous clinical traials.These combinations are cosidered as standard treatment in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes.

A dose attenuated schedule of irinotecan and capecitabine in combination with celecoxib in advanced colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3584-3584
Author(s):  
B. F. El-Rayes ◽  
A. F. Shields ◽  
U. Vaishampayan ◽  
L. K. Heilbrun ◽  
M. M. Zalupski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Free Survival ◽  
Study Results ◽  
Cox 2

3584 Background: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in the majority of colorectal cancers. Inhibition of the COX-2 enzyme can sensitize colorectal cancer cells to the apoptotic effects of chemotherapeutic agents and block angiogenesis. This phase II study was undertaken to determine the effects of adding celecoxib to a dose attenuated irinotecan and capecitabine regimen. Methods: The primary objective was to estimate the objective response rate of patients with metastatic colorectal cancer treated with irinotecan, capecitabine, and celecoxib. Previously untreated patients, except for adjuvant therapy, with metastatic colorectal adenocarcinoma were eligible for this study. Patients received irinotecan 70 mg/m2 (over 30 minutes) on days 1 and 8, and capecitabine 2,000 mg/m2/day from day 1 to 14 of a 21-day cycle. Celecoxib was administered at a dose of 400 mg twice-daily starting on day -7 until termination from study. Results: A total of 51 patients (median age 58 years) have been enrolled on the study. The results presented are for the first 48 patients registered to the study. Median performance status was 1. A median number of 5.5 cycles (range 0- 18) were administered. In an intention to treat analysis, objective response rate was 50%. The median progression free survival was 6.9 months (90%CI; 4.7–8.2). Median survival is ≥19.4 months. No treatment related deaths were observed. The only grade 4 toxicity was diarrhea in 2 (4%) patients. Grade 3 toxicities were diarrhea (33%), hand-foot syndrome (8%), nausea (13%), vomiting (8%) and neutropenia (12%). Conclusion: Lowering the dose intensity of irinotecan in this study did not appear to compromise the treatment outcome and markedly improved the therapeutic index of this combination. Celecoxib can be safely administered in combination with irinotecan and capecitabine. Based on the observed progression free survival and response rate, the regimen has promising activity. No significant financial relationships to disclose.

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.

Down-regulation of KRAS-interacting miRNA-143 to predict prognosis and response to EGFR-targeted agents in colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14066-e14066
Author(s):  
Florian Eisner ◽  
Michael Stotz ◽  
Hellmut Samonigg ◽  
Sigurd Lax ◽  
Gerald Hoefler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Targeted Agents ◽  
Wild Type ◽  
Down Regulation ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Expression Levels

e14066 Background: MicroRNA-143 is frequently down-regulated in colorectal cancer (CRC) and influence CRC cell proliferation, apoptosis and sensitivity to 5-fluorouracil. mRNA encoded by the KRAS oncogene has been identified as a target of microRNA-143. However, the prognostic significance of microRNA-143 expression and the ability to predict the patient response to EGFR-targeted agents have not been explored yet. Methods: In this study, we analyzed 77 CRC harboring wild-type KRAS and obtaining treatment with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. MicroRNA-143 expression was measured by RT-PCR in both CRC and corresponding non-neoplastic colon tissue and the expression levels were correlated with clinico-pathological characteristics. Cancer-specific survival was calculated by uni- and multivariate analyses. The progression-free survival and objective response rates on EGFR-targeted therapy were also evaluated. Results: Down-regulation of microRNA-143 was observed in 47/77 (61%) CRC. Multivariate Cox regression analysis identified low levels of microRNA-143 expression as an independent prognostic factor with respect to cancer-specific survival (HR=1.92, CI=1.1-3.4, p=0.024). A significant difference was observed with respect to progression-free survival on EGFR-targeted therapy (p=0.031, log-rank test), but there were no significant differences with regard to the objective response rate. Conclusions: Our data suggest that microRNA-143 expression levels serve as independent prognostic biomarker for KRAS wild-type CRC patients but not as predictor for EGFR-targeted therapy. In addition, we consider microRNA-143 as a potential drug target for future therapy of CRC.

scholarly journals Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer

JAMA ◽  
2019 ◽  
Vol 321 (14) ◽  
pp. 1370 ◽  
Author(s):  
Kimmie Ng ◽  
Halla S. Nimeiri ◽  
Nadine J. McCleary ◽  
Thomas A. Abrams ◽  
Matthew B. Yurgelun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Vitamin D3 ◽  
Standard Dose ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Vitamin D3 Supplementation

Phase II multicenter study of second-line FOLFIRI plus cetuximab (FLIER) in patients with KRAS wild-type metastatic colorectal cancer: Final analysis of survival and additional analysis of BRAF, PI3CA mutations.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 481-481 ◽  
Author(s):  
Yasuhiro Miyake ◽  
Shigeyoshi Iwamoto ◽  
Shoichi Hazama ◽  
Fuminori Goda ◽  
Chu Matsuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Predictive Biomarker ◽  
Second Line ◽  
Wild Type ◽  
Braf Mutations

481 Background: Survival advantage of second line FOLFIRI plus cetuximab in patients with KRAS wild-type metastatic colorectal cancer has not been well reported. Since mutations in codons 12 and 13 of the KRAS gene predict lack of response to Cetuximab, mutations of V600E BRAF and PI3CA have been controversial. Methods: The aim of this study was to assess the efficacy of second-line FOLFIRI plus cetuximab in KRAS wt mCRC. Primary endpoint was response rate, other secondary endpoints were PFS, OS and safety. KRAS, BRAF, PI3CA tests by direct sequence were performed in Yamaguchi University. The starting dose of irinotecan was 150mg/ m2 (approved dose in Japan), but decreased to 100mg/m2 with UGT1A1 *28,*6 homozygous or both heterozygous. Results: From December 2008 to November 2009, 112 pts were preregistered. 67 (59.8%) pts were KRAS codon 12, 13 wt, and 60 pts were enrolled: 39 males (65%), 21 females (35%); median age was 62 years (range 37-82). The incidence of UGT1A1*28, *6 homozygous was 2.8%, 4.7% respectively. Grade 3/4 adverse events were leucopenia 26.7%, neutropenia 43.3%, paronychia 10.0%, skin toxity (fissure) 10.0% and acne 5.0%. The confirmed response rate (RECIST) was 31.7% (19/60). The median progression free survival and overall survival were 7.5 (C.I. 5.2-10.1) and 19.5 (C.I. 11.7-22.2) months respectively. Three pts had BRAF mutations and tumor shirinkage were +50.9%, +12%, +85.6% respectively. Two pts had PI3CA mutations and tumor shirinkage were +4%, +44%, respectively. Conclusions: FLIER was the first multicenter phase II trial with prospective analysis of KRAS as a predictive biomarker for cetuximab in second-line mCRC in Japan. Second-line FOLFIRI+cetuximab is well-tolerated and active. Mutations in BRAF and PI3CA gene seemed to be lack of response to cetuximab.

Fruquintinib in patients with metastatic colorectal cancer failed in previously bevacizumab-based therapy: A monocentric retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15555-e15555
Author(s):  
Xiaoqiang Gu
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Safety Profile ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Forest Plot ◽  
Lasso Regression ◽  
Standard Regimen

e15555 Background: Fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is a new targeting anti-cancer agent for refractory metastatic colorectal cancer (mCRC). Promising antitumor effect of fruquintinib monotherapy was verified in a phase III FRESCO randomized study of mCRC patients, and only 30% patients were prior bevacizumab-treated. However, comprehensive effect evaluation of fruquintinib in mCRC patients who have previously failed in bevacizumab therapy were scarce. Methods: Forty patients with metastatic CRC who had previously failed at least 2 lines of standard regimen containing bevacizumab in Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine from March 2019 to February 2020 were enrolled. These patients were administrated with fruquintinib (5mg orally, once daily) in cycles of 3 weeks on/ 1 week off. Furthermore, the primary endpoint was overall survival (OS). Secondary endpoints mainly included progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and safety profile. Statistical analyses were performed using IBM SPSS statistics software and ‘R’ statistical software with the ‘forest plot’ package. Subsequently, the variables were screened and verified through LASSO regression with the R software “glmnet” package. Results: The mOS was 8.1months (95%CI, 5.6667-12.8667), mPFS was 4.1833 months (95% CI, 3.5333-5.0667), and DCR was 65% (26 SD in 40 patients). Particularly, gender (HR: 7.11, 95%CI:1.86-27.16,P = 0.005), age (HR:0.91, 95%CI:0.85-0.98,P = 0.012), ECOG(HR:3.75, 95%CI:1.13-12.42,P = 0.03), medication duration (HR:0.62, 95%CI:0.48-0.81,P＜0.001),and the number of metastases(HR:2.95,95%CI:1.21-7.18,P = 0.017) identified the statistically significant association with OS. Eliminating the influence of time factor, ECOG and medication cycle obtained by Lasso regression were the risk factors for OS. The most frequently reported adverse events were mainly hypertension, proteinuria, hand-foot skin reaction, fatigue and diarrhea, and any new safety signals were not observed. Conclusions: Fruquintinib showed an acceptable safety profile and promising efficacy in patients with metastatic colorectal cancer failed in previously bevacizumab-based therapy. Future studies of fruquintinib should focus on identifying the patients most likely to benefit and on minimizing toxicity.

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