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Fundamentals of iRECIST and Oncology Trial Endpoints MERIT Webinar Key Takeaways

iRECIST provides guidance for solid tumor response criteria in immunotherapy to accommodate possible pseudoprogression, which may occur in some subjects. In this presentation, MERIT discussed the rules and principles of iRECIST, imaging endpoints, and special considerations for using iRECIST response criteria.

Summary:

Purpose and Indication of iRECIST

  • Modification of RECIST 1.1 for immunotherapy drugs which can cause pseudoprogression of solid tumors
  • Provide objective methodology of tumor response to immunotherapeutic agents to support clinical trial endpoints

Pseudoprogression

  • An increase in the size of lesions, or the visualization of new lesions, followed by a response; this may occur in approximately 6% of subjects
  • Seen in Immunotherapy agents which inhibit PD-1 or CTLA-4

iRECIST Follows Many Standards of RECIST 1.1 Except for:

  • When new lesion(s) appear at a follow up timepoint, the radiologist will categorize and record new lesions as following:
    • New Lesion-Target (NL-T)
      • Sum of diameter is recorded separately from diameter of target lesion
      • Up to 5 per subject, maximum of 2 per organ
    • New Lesion-Non target (NL-NT): New lesions that were not selected as NL-T are assessed qualitatively
  • New nomenclature: In iRECIST CR, PR, SD, and NN are named iCR, iPR, iSD, and iNN respectively by adding letter “i” for iRECIST or immunotherapy
  • Timepoint response after PD
  • Unconfirmed Progressive Disease (iUPD)
    • May occur multiple times (e.g., iCR-iUPD-iUPD, or iCR-iUPD-iPR-iUPD)
    • Same definition as RECIST 1.1 PD
  • Confirmed Progressive Disease (iCPD)
    • Only comes right after iUPD if progression is confirmed at next visit (4-6 weeks from initial iUPD)
    • iCPD must meet the following requirements
      • If the original cause of iUPD in one timepoint worsens in subsequent timepoint
        • Lesion categories that have resulted in iUPD worsen
          • TL: if SOD increased 5 mm or more
          • NTL: if any increase is seen
          • NL-T: if NL-T SOD increases 5 mm or more
          • NL-NT: if any increase is seen, or if any additional new lesion appears
        • It can be one lesion category or multiple lesion categories
      • If the lesion category that did not cause iUPD in previous timepoint meets RECIST 1.1 PD requirements at current timepoint
    • iUPD is not confirmed if it doesn’t meet requirements for iCPD, then another iUPD is assigned
    • If lesion category assessment is improved and back to iCR, iPR, or iSD threshold, then response is given accordingly
  • Collection of reason why progression cannot be confirmed (may be predefined list of reasons per protocol or imaging charter)
  • Collection of clinical status of patient
    • Assessed subjectively/qualitatively by provider in re: patient’s performance status and disease related symptoms
    • Handled as clinical data from site (as the finalized interpretation from the local provider)
      • Clinically stable or clinically unstable

Special Considerations for iRECIST:

  • Backdate the date of progression when iCPD occurs
    • The Date of PD will the first iUPD that eventually becomes iCPD
  • Responses after iUPD due to NL
    • Presence of new lesion can still result in response
    • When new lesion is stable in their size without causing iCPD
    • In such cases, iUPD can be given when:
      • Additional NL
      • NL-T meets RECIST 1.1 criteria of PD (20% increase)
      • NL-NT meets RECIST 1.1 criteria of PD (Unequivocal increase or approximately 73% of overall increase)
  • Non-Target Assessment – Qualitative assessment
    • No change from baseline or nadir (NC)
    • Increased from baseline or nadir (INC)
    • No change from last assessment (NCLA): to be used after NTL iUPD
    • Further increase from last assessment (INCLA): to be used after NTL iUPD
    • Unequivocal increase (UNE)
  • iRECIST is unvalidated response criteria
    • RECIST 1.1 is still standard and well-received criteria for solid tumor for regulatory fields
    • iRECIST often becomes exploratory endpoint

What Are Some Common Mistakes with iRECIST?

  • Nadir: When PD range is calculated, always use the Nadir, the lowest sum of diameter from the whole timepoint available regardless of iUPD recurrence
  • iCPD from iUPD by Non-Target Lesion: Non-Target Lesion or New lesion Non-Target causing iUPD occurs with any further increase, doesn’t need to be unequivocal increase
  • Target Lesion response weighs more. After iUPD, if target lesion becomes iCR, iPR, or iSD
    • AND Non-target lesion and/or new lesions has not changed from iUPD or non-iUPD
    • Target lesion trumps, and the overall response follows the target lesion response

HIGHLIGHTS FROM Q & A

Q In determining iUPD (100mm) to iUPD (102mm) to (105mm) for target lesions, would this third timepoint be iCPD from the 5mm increase from the original iUPD?
A Yes. The 5 mm increase that triggers iCPD can either be a total of 5 mm over several timepoints as described here, or it can be a 5 mm increase at a single timepoint.

Benefits of MERIT Oncology Solutions:

Comprehensive Imaging Services: We provide end-to-end central oncology imaging services from acquisition and upload, to storage, QC review, blinded independent review, and data export.

Single System: Unlike others that depend on separate applications, our proprietary software, EXCELSIOR™, delivers automation in a single system for all image and workflow management that supports lesion segmentation with the corresponding response criteria such as iRECIST.

Collaborative Partnership: We prioritize a collaborative, partnership-driven approach for all projects with scalable solutions and personalized attention. We adapt quickly to meet your needs. If you’re looking for an oncology imaging services provider that will value your partnership and make your study a priority, consider MERIT.

View full webinar video here

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