# Presentation: 525560

## 3 Year DFS vs. 5 Year OS as an endpoint for Adjuvant Colon Cancer Studies:  Data from Randomized Trials  

- D Sargent1, S Wieand2, R Goldberg1, M O’Connell2, A Benson3, P Catalano3, J Benedetti4, G Francini5, L Shepherd6, JF Seitz7, R Labianca8** **

- 1Mayo Clinic-NCCTG, 2NSABP, 3ECOG, 4SWOG, 5University of Siena (Italy), 6NCIC-CTG (Canada), 7University of the Mediterranean (France), 8Ospedali Riuniti (Italy)** **

## Disclosure

- Very preliminary work
- Further analyses underway
- Not for distribution or citation

## Suggestion	

- 3 year disease free survival (DFS) is an appropriate endpoint to replace 5 year overall survival (OS) as an endpoint in adjuvant colon trials
- Would allow more rapid completion, reporting of trials

## Methods

- Data from large randomized trials
- Individual patient data (when available), or investigator furnished summaries.
- Compare 3 year DFS, 5 year OS for each arm
- Compare difference between ‘control’ and experimental arms
- Weighted linear regression

- *Did not include a no treatment control arm

- Total:  38 treatment arms

## 3 year DFS vs 5 year OS

**~1980:             C01          NCCTG-784852**

## 3 year DFS vs 5 year OS

**~1985: INT0035    CO2**

## 3 year DFS vs 5 year OS

**~1988:                 NCIC            NCCTG-874651 Siena                  FFCD                GIVIO**

## 3 year DFS vs 5 year OS

**~1990:       INT0089   NCCTG-894651**

## 3 year DFS vs 5 year OS

**~1995:      NCCTG-914653**

## 3 year DFS vs 5 year OS

## Results

- Regression equation:
- 3 yr DFS=0.05+.93*5 yr OS
- Coefficients not significantly different from 0 and 1
- Correlation 0.92, R2 = 0.85
- Largest difference 6%, 36 of 38 _<_ 3% difference

## Conclusion (1)

- On an arm by arm basis, 3 year DFS is an excellent predictor of 5 year OS
- Event rates virtually identical
- No impact on sample size
- Power for 3 yr DFS will adequately power 5 yr OS

## Within study comparisons

- Does a comparison of arms using 3 yr DFS reach the same conclusion as using 5 yr OS?

## 3 year DFS vs 5 year OS

##  3 yr DFS > 5 yr OS

-  3 yr DFS > 5 yr OS
- 	6 ‘Experimental’
- 	3 ‘Control’

-  3 yr DFS < 5 yr OS
- 	5 ‘Experimental’
- 	7 ‘Control’

##  Difference in 3 yr DFS vs Difference in 5 yr OS

-  Difference in 3 yr DFS vs Difference in 5 yr OS

- In 8 of 16 within study
- comparisons, difference
- in 3 yr DFS > difference
- in 5 yr OS, 4 had the same
- difference.

## Results

- Regression equation:
-   5 yr OS = 0.85*  3 yr DFS
- Correlation 0.87
- R2 = 0.75
- Of 16 total comparisons
- 12 same conclusion both DFS & OS
- 9 No difference, 3 significant difference
- 3 significant only for DFS
- 1 significant only for OS

## Conclusion (2)

- As an endpoint for comparison, 3 yr DFS  may slightly overestimate 5 yr OS 
- May change the conclusion in a non-trivial proportion of trials
- If long-term OS is what we really care about, conclusions based on 3 yr DFS must be considered ‘subject to confirmation’

## Discussion

- Did not have individual patient data from all trials
- Most had a no treatment control
- Need to study more trials with ‘active’ treatment in all arms
- B’s and C’s mixed together, may be beneficial to separate
- Relevance for non-cytotoxic agents

## Future work

- More trials
- Mimic actual trial conduct
- Recreate dataset that would have been available at each given time-point
- Other endpoints: 2 yr DFS, 3 yr OS