Anti-PD-1 Antibody Plus Regorafenib in Refractory Microsatellite Stable Metastatic Colorectal Cancer

Efficacy and Safety of Anti-PD-1 Antibody Plus Regorafenib in Refractory Microsatellite Stable Metastatic Colorectal Cancer: a Retrospective Single-arm Cohort Study

Managements for refractory proficient mismatch repair (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC) were still challenging and controversial. Our study sought to investigate the efficacy and safety of anti-PD-1 antibodies plus regorafenib in refractory pMMR/MSS mCRC between July 2019 and June 2021 at the Hunan Cancer Hospital.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Adenocarcinoma
• Intervention / Treatment: Drug: regorafenib plus anti-PD-1 antibodies

Detailed Description

We retrospectively analyzed the efficacy and safety of 103 pMMR/MSS mCRC patients treated with at least one dose of anti-PD-1 antibodies plus regorafenib (80 mg once daily for 21 days on/7 days off 28 days as a cycle) between July 2019 and June 2021 at the Hunan Cancer Hospital. All patients had previously received at least second-line treatment. The patients were evaluated by computed tomography every 2 or 3 treatment cycles until progression or being lost to follow-up. The primary end point was overall survival (OS).

• Study Type: Observational
• Enrollment (Actual): 103

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 1 cycle of anti-PD-1 antibodies plus regorafenib between July 2019 and June 2021 at the Hunan Cancer Hospital.

Description

Inclusion 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).

  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) 0 or 1 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?

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: July 4, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Colorectal cancer;regorafenib;anti-PD-1 antibodies
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies; Immune Checkpoint Inhibitors
• Other Study ID Numbers: REGOPD-1-Hunan

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