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

• ClinicalTrials.gov Identifier: NCT06031376
• Recruitment Status: Completed
• First Posted: September 11, 2023
• Last Update Posted: September 11, 2023
• Sponsor: Hunan Cancer Hospital
• Information provided by (Responsible Party): Hunan Cancer Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Metastatic Colorectal Adenocarcinoma	Drug: Fruquintinib; Drug: PD-1 inhibitors; Drug: Trifluridine/Tipiracil; Drug: Bevacizumab

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 Design

• Study Type: Observational
• Actual Enrollment: 106 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Fruquintinib With PD-1 Inhibitors Versus TAS-102 With Bevacizumab in Late-Line mCRC: A Retrospective Cohort Study Based on Propensity Score Matching
• Actual Study Start Date: July 1, 2019
• Actual Primary Completion Date: October 31, 2022
• Actual Study Completion Date: March 31, 2023

Groups and Cohorts

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 Name: 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: TAS-102; Lonsurf; S 95005; Drug: Bevacizumab; Bevacizumab 5 mg /kg, intravenously on days 1,15,every 28 days; Other Name: Avastin

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Approximately 12 months ]
   Overall survival defined as the observed time elapsed between the date of commencement of treatment and the date of death due to any cause

Secondary Outcome Measures :

1. Progression-free survival (PFS) [ Time Frame: Approximately 12 months ]
   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.
2. Overall response rate (ORR) [ Time Frame: Approximately 12 months ]
   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
3. Disease control rate (DCR) [ Time Frame: Approximately 12 months ]
   Disease control rate has been defined as the addition of (CR + PR) rate and also stable disease (SD) rate
4. Treatment-Related Adverse Events (TRAE) [ Time Frame: Approximately 12 months ]
   Treatment-Related Adverse Events (TRAE) as assessed by CTCAE v5.0, including serious adverse events (SAEs)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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.

Criteria

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.

Contacts and Locations

Locations

China, Hunan

Hunan Cancer hospital

Changsha, Hunan, China

Sponsors and Collaborators

Hunan Cancer Hospital

Investigators

• Principal Investigator: Rongrong li, professor; Hunan Cancer Hospital

More Information

• Responsible Party: Hunan Cancer Hospital
• ClinicalTrials.gov Identifier: NCT06031376
• Other Study ID Numbers: FPTB-01
• First Posted: September 11, 2023
• Last Update Posted: September 11, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: please contact the principal investigator of this study or correspondence author.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hunan Cancer Hospital:

Colorectal cancer; Fruquintinib;PD-1;TAS-102; bevacizumab

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Trifluridine; Bevacizumab; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Antiviral Agents; Anti-Infective Agents