Fruquintinib With PD-1 Inhibitors Versus TAS-102 With Bevacizumab in Late-Line mCRC

Study Overview
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Brief Summary
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Fruquintinib with PD-1 inhibitors (FP) and TAS-102 with bevacizumab (TB) are two common therapies for patients with previous-treated metastatic colorectal cancer (mCRC). However, it's still not clear that which therapy can bring better prognosis. Our study sought to investigate the efficacy and safety of fruquintinib with PD-1 Inhibitors versus TAS-102 with bevacizumab in Late-Line mCRC between July 2019 to October 2022July 2019 and June 2021 at the Hunan Cancer Hospital.

Detailed Description
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This is a retrospective cohort study conducted in Hunan Cancer Hospital. Patients (pts) with mCRC who had received at least the 2nd line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two arms. Overall survival (OS) was set as the primary endpoint. From July 2019 to October 2022, 106 eligible pts in total were enrolled. According to the treatment received, 72 and 34 pts were respectively allocated into FP cohort and TB cohort.

Official Title
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Fruquintinib With PD-1 Inhibitors Versus TAS-102 With Bevacizumab in Late-Line mCRC: A Retrospective Cohort Study Based on Propensity Score Matching

Conditions
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Metastatic Colorectal Adenocarcinoma

Intervention / Treatment
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* Drug: Fruquintinib
* Drug: PD-1 inhibitors
* Drug: Trifluridine/Tipiracil
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded). Have progressed from at least 2 lines of standard treatment,including fluoropyrimidines, irinotecan, oxaliplatin, with or without targeted drugs, like bevacizumab and cetuximab (only for RAS wild-type). Regorafenib was permitted but not required for inclusion. Has measurable or non-measurable disease as defined by RECIST version 1.1 Is able to swallow oral tablets. Estimated life expectancy ≥12 weeks. Eastern Cooperative Oncology Group performance status (ECOG PS) less than 2 Has adequate organ function. Exclusion Criteria: Pregnancy, lactating female or possibility of becoming pregnant during the study. Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy (excluding alopecia, and skin pigmentation). Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease. Has severe or uncontrolled active acute or chronic infection. Known carriers of HIV antibodies. Confirmed uncontrolled arterial hypertension or uncontrolled or symptomatic arrhythmia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fruquintinib plus PD-1 inhibitors<br>In fruquintinib plus PD-1 inhibitors group,The patients were treated orally with Fruquintinib (5mg once daily for 14 days on/7 days off, over a 21-day cycle), combined with 1 of the 5 anti-PD-1 antibodies (i.e., nivolumab, pembrolizumab, camrelizumab, sintilimab, or toripalimab). The anti-PD-1 antibody was administered intravenously on day 1, and its recommended dosage was as follows: nivolumab: 240 mg, every 2 weeks; pembrolizumab, camrelizumab, and sintilimab: 200 mg every 3 weeks; and toripalimab: 240 mg every 3 weeks. | Drug: Fruquintinib<br>* 5mg once daily for 14 days on/7 days off, over a 21-day cycle<br>Drug: PD-1 inhibitors<br>* The anti-PD-1 antibody was administered intravenously on day 1, and its recommended dosage was as follows: nivolumab: 240 mg, every 2 weeks; pembrolizumab, camrelizumab, and sintilimab: 200 mg every 3 weeks; and toripalimab: 240 mg every 3 weeks.<br>* Other names: anti-PD-1 antibodies;|
| TAS-102 plus bevacizumab<br>In TAS-102 plus BEV group, Patients received TAS-102 (35 mg/m²orally twice a day on days 1-5 and 8-12, every 28 days) and bevacizumab (5 mg /kg, intravenously, on days 1 and 15, every 28 days). Bevacizumab was approved to be a 30-minute intravenous infusion before TAS-102. | Drug: Trifluridine/Tipiracil<br>* TAS-102 35 mg/m²orally twice a day on days 1-5 and 8-12, every 28 days<br>* Other names: S 95005;Drug: Bevacizumab<br>* Bevacizumab 5 mg /kg, intravenously on days 1,15,every 28 days<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival defined as the observed time elapsed between the date of commencement of treatment and the date of death due to any cause | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival defined as the time elapsed between the date of commencement of treatment and the date of radiologic tumour progression according to RECIST version 1.1 by investigator's judgement or death from any cause, whichever comes first. | Approximately 12 months | 
| Overall response rate (ORR) | Overall response rate (ORR) was regarded as the proportion of complete responses (CRs) and partial responses (PRs) according to RECIST version 1.1 criteria and using investigator's tumor assessment | Approximately 12 months | 
| Disease control rate (DCR) | Disease control rate has been defined as the addition of (CR + PR) rate and also stable disease (SD) rate | Approximately 12 months | 
| Treatment-Related Adverse Events (TRAE) | Treatment-Related Adverse Events (TRAE) as assessed by CTCAE v5.0, including serious adverse events (SAEs) | Approximately 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer; Fruquintinib;PD-1;TAS-102; bevacizumab