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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Adenocarcinoma
• Intervention / Treatment: Drug: Trifluridine/Tipiracil; Drug: Bevacizumab; Drug: Fruquintinib; Drug: PD-1 inhibitors

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 106

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study population were the patients treated with at least 2 cycle of fruquintinib plus PD-1 Inhibitors or TAS-102 plus BEV in patients suffering refractory mCRC from July 2019 to October 2022 at the Hunan Cancer Hospital.

Description

Inclusion Criteria:

1. Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded).
2. 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.
3. Has measurable or non-measurable disease as defined by RECIST version 1.1
4. Is able to swallow oral tablets.
5. Estimated life expectancy ≥12 weeks.
6. Eastern Cooperative Oncology Group performance status (ECOG PS) less than 2
7. Has adequate organ function.

Exclusion Criteria:

1. Pregnancy, lactating female or possibility of becoming pregnant during the study.
2. Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy (excluding alopecia, and skin pigmentation).
3. Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
4. Has severe or uncontrolled active acute or chronic infection.
5. Known carriers of HIV antibodies.
6. Confirmed uncontrolled arterial hypertension or uncontrolled or symptomatic arrhythmia.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fruquintinib plus PD-1 inhibitors; 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; 5mg once daily for 14 days on/7 days off, over a 21-day cycle; Drug: PD-1 inhibitors; 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.; Other Names: anti-PD-1 antibodies
TAS-102 plus bevacizumab; 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; TAS-102 35 mg/m²orally twice a day on days 1-5 and 8-12, every 28 days; Other Names: Lonsurf; TAS-102; S 95005; Drug: Bevacizumab; Bevacizumab 5 mg /kg, intravenously on days 1,15,every 28 days; Other Names: Avastin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hunan Cancer Hospital
• Investigators: Principal Investigator: Rongrong li, professor, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: September 2, 2023
• First Submitted That Met QC Criteria: September 2, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 2, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Colorectal cancer; Fruquintinib;PD-1;TAS-102; bevacizumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Immune Checkpoint Inhibitors; Trifluridine
• Other Study ID Numbers: FPTB-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for principal investigator or correspondence author]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: please contact the principal investigator of this study or correspondence author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No