Response to treatment

The purpose of this page is to create a central repository of general and disease-specific response criteria. These are divided into three categories: strong, intermediate, and weak endpoints. See the Levels of Evidence page and individual page's response criteria sections for more details.

Strong endpoints

• Overall survival (OS)
• All-cause mortality
• Disease-specific mortality

Intermediate surrogate endpoints

These are almost all measures of time interval between diagnosis and/or start of treatment, and a predefined event such as cancer recurrence, cancer progression, or a composite outcome. We will expand this section over time, including adding literature that supports the use of a surrogate end point for disease-specific scenarios.

Event-free survival (EFS)

Events sometimes defined differently, but usually include relapse, progression, and death from any cause.

References

1. Maurer MJ, Ghesquières H, Jais JP, Witzig TE, Haioun C, Thompson CA, Delarue R, Micallef IN, Peyrade F, Macon WR, Jo Molina T, Ketterer N, Syrbu SI, Fitoussi O, Kurtin PJ, Allmer C, Nicolas-Virelizier E, Slager SL, Habermann TM, Link BK, Salles G, Tilly H, Cerhan JR. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014 Apr 1;32(10):1066-73. Epub 2014 Feb 18. link to PMC article PubMed

Failure-free survival (FFS)

Defined as the absence of an additional systemic therapy, relapse, or non-relapse mortality.

Primary refractory disease

In leukemia, generally refers to the failure to achieve CR or CR_i after two courses of intensive induction.

Progression-free survival (PFS)

The most commonly used surrogate time-based measure.

References

1. Wang X, Wang X, Hodgson L, George SL, Sargent DJ, Foster NR, Ganti AK, Stinchcombe TE, Crawford J, Kratzke R, Adjei AA, Kindler HL, Vokes EE, Pang H. Validation of progression-free survival as a surrogate endpoint for overall survival in malignant mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) trials. Oncologist. 2017 Feb;22(2):189-198. Epub 2017 Feb 10. link to PMC article PubMed

Relapse-free interval (RFI)

Not commonly used outside of the adjuvant setting.

Recurrence- or Relapse-free survival (RFS)

Not commonly used outside of the adjuvant setting. May have slightly varied definitions:

• Defined as the interval from date of randomization to first evidence of recurrence

References

1. Suciu S, Eggermont AMM, Lorigan P, Kirkwood JM, Markovic SN, Garbe C, Cameron D, Kotapati S, Chen TT, Wheatley K, Ives N, de Schaetzen G, Efendi A, Buyse M. Relapse-free survival as a surrogate for overall survival in the evaluation of stage II-III melanoma adjuvant therapy. J Natl Cancer Inst. 2018 Jan 1;110(1). link to original article PubMed

Weak surrogate endpoints

This category includes all surrogate measures that are based on objective response to treatment, without a patient-specific survival component. The most frequently reported weak surrogate endpoint in non-randomized trials is the objective response rate (ORR), usually using the RECIST criteria. Note that many of these weak surrogate endpoints have been correlated with survival endpoints, with the general maxim being patients who respond to therapy are more likely to achieve remission, remain in remission, and therefore have a longer cancer-specific and overall survival. Regardless, we annotate RCTs by their stated primary endpoint, unless the primary endpoint is positive AND a stronger secondary endpoint has a statistically significant finding.

General response rates

• Response rate (RR) A generic term that can be any of the below
• Objective or overall response rate (ORR) Definition may vary across cancer subtypes but usually this is a sum of the CR + PR rates.
• Disease control rate (DCR) Usually this is the sum of the CR + PR + SD rates.
• Clinical feasibility rate Defined as no grade 4 neutropenia/thrombocytopenia or thrombocytopenia with bleeding, no grade 3/4 febrile neutropenia or non-hematological toxicity; no premature withdrawal/death.

Morphologic response rates

• Definitions may vary across cancer subtypes:
  • Complete response rate (CR rate)
  • Minimal response rate (MR rate)
  • Partial response rate (PR rate)
  • Stable disease rate (SD rate)
  • Unconfirmed complete response rate (CRu rate)

RECIST criteria

• RECIST 1.1: Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. PubMed
• iRECIST: Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litière S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EG; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. Epub 2017 Mar 2. link to original article link to PMC article PubMed
• imRECIST: Hodi FS, Ballinger M, Lyons B, Soria JC, Nishino M, Tabernero J, Powles T, Smith D, Hoos A, McKenna C, Beyer U, Rhee I, Fine G, Winslow N, Chen DS, Wolchok JD. Immune-modified Response Evaluation Criteria In Solid Tumors (imRECIST): refining guidelines to assess the clinical benefit of cancer immunotherapy. J Clin Oncol. 2018 Mar 20;36(9):850-858. Epub 2018 Jan 17. link to original article PubMed

Neoadjuvant response rates

• Good response rate
  • In Breast cancer, a score of 3, 4, or 5 on the Miller-Payne scoring system
• Objective clinical response (OCR rate)
• Pathologic complete response rate (pCR rate)

Hematology-specific response rates

• Complete response with incomplete hematologic recovery rate (CR_i rate)
• Complete response without minimal residual disease rate (CR_MRD- rate)
• Complete response with minimal residual disease rate (CR_MRD+ rate)
• Major cytogenetic reponse (MCyR)
• Major hematologic response (MaHR)
• Minor hematologic response (MiHR)
• Overall hematologic response (OHR)

Leukemia-specific response rates

• Morphologic leukemia-free state (MLFS)
• No evidence of leukemia (NEL)

Multiple myeloma-specific response rates

• Near complete response rate (nCR rate)
• Stringent complete response rate (sCR rate)
• Very good partial response rate (VGPR rate)