1. MJ O’Connell for the ACCENT Collaborative Group
Survival Following Recurrence in Patients with Adjuvant Colon Cancer: Findings from the ACCENT Dataset
MJ O’Connell for the ACCENT Collaborative Group

2. Goal of This Study
Utilize the collaborative ACCENT database to examine four possible prognostic factors in patients with tumor recurrence following treatment for stage II or III colon cancer

3. Trials Included Total: 17 trials; 17,381 pts 3517 QUASAR 867 GIVIO 905
GERCOR
718
NSABP C02
3547
INT 0089
773
NSABP C01
1078
SWOG 9415
259
FFCD
878
N914653
359
NCIC
915
N894651
239
Siena
2176
NSABP C05
408
N874651
2151
NSABP C04
926
INT 0035
1081
NSABP C03
247
N784852 N
Trial
Active Control
No Treatment Control
Total: 17 trials; 17,381 pts

4. Prognostic Factors Examined
Time from randomization on surgical adjuvant protocol to tumor recurrence (<1, 1-2, 2-3, 3-4, >4 years)
Initial stage of colon cancer (II, III)
5FU-based adjuvant therapy vs surgery alone
Era patient entered onto surgical adjuvant protocol ( , , )

5. Methods
Analyses were restricted to only those patients who recurred after initial therapy
Univariate analyses performed using Kaplan-Meier methods and log-rank testing
Cox proportional hazards models, stratified by study, used for multivariate analyses
Interaction tests between each factor and the baseline variables of age, gender, tumor site, and initial stage performed using a likelihood ratio test
Analysis of prognostic value of initial treatment was limited to patients randomized to 5FU-based treatment versus surgery alone

6. Results
Median follow-up of patients still alive: 8 years from randomization, 30.5 months from tumor recurrence
5,722 of 17,381 patients (32.9%) experienced tumor recurrence
Overall median survival following recurrence was 13.1 months
No data regarding tumor characteristics or treatment at time of recurrence is available

7. Selected Patient Characteristics
Percent
Stage II
20%
III
80%
Treatment
Surgery alone
16%
Surgery plus chemotherapy
84%

8. Time from Recurrence to Death
by Year of Recurrence
100
Year 0- 1 (N=1846)
Year 1-2 (N=1854)
Year 2-3 (N=924)
Year 3-4 (N=516)
Year 4+ (N=582)
Total (N=5722) 80 60
% Alive 40
Log Rank P-Value = <0.0001 20 1 2 3 4 5 6 7 8
Time (Years)

9. Time from Recurrence to Death by
Year of Recurrence for Stage II Patients
100
Year 0-1 (N=311)
Year 1-2 (N=351)
Year 2-3 (N=198)
Year 3-4 (N=118)
Year 4+ (N=175)
Total (N=1153) 80 60
% Alive 40
Log Rank P-Value = 20 1 2 3 4 5 6 7 8
Time (Year)

10. Time from Recurrence to Death by
Year of Recurrence for Stage III Patients
100
Year 0-1 (N=1533)
Year 1-2 (N=1499)
Year 2-3 (N=724)
Year 3-4 (N=394)
Year 4+ (N=400)
Total (N=4550) 80 60
% Alive 40
Log Rank P-Value = <0.0001 20 1 2 3 4 5 6 7 8
Time (Year)

11. Time from Recurrence to Death by Stage
100
Stage II (N=1153)
Stage III (N=4550)
Total (N=5703) 80 60
% Alive
Log Rank P-Value = <0.0001 40 20 1 2 3 4 5 6 7 8
Time (Years)

12. Time from Recurrence to Death by Era
100
(N=628)
(N=3904) 80
(N=1190)
Total (N=5722) 60
% Alive 40
Log Rank P-Value = <0.0001 20 1 2 3 4 5 6 7 8
Time (Years)

13. Time from Recurrence to Death by Adjuvant Treatment vs. Surgery Alone
100
Surgery Alone (N=916)
Adjuvant Treatment (N=754)
Total (N=1670) 80 60
% Alive 40
Log Rank P-Value = 20 1 2 3 4 5 6 7 8
Time (Years)

14. Forest Plot of Multivariate Model Hazard RatiosCM

15. Forest Plot of Multivariate Model Hazard Ratios by Stage
Time to Recurrence
Era
Initial Trt
Time to Recurrence
Era
Initial Trt
Hazard Ratio CM

16. Conclusions
Time from initial surgery and stage of the primary colon cancer were important prognostic variables in patients with recurrent colon cancer
Patients who have recurrent tumor following 5FU-based adjuvant therapy had worse prognosis than those without adjuvant chemotherapy
Survival following recurrence improved from

17. Clinical Research Implications
These prognostic factors should be taken into consideration in the design and analysis of treatment protocols for recurrent colon cancer
Differences in clinical behavior of stage II and stage III colon cancer were identified
The importance of contemporary (rather than historical) controls to evaluate treatment benefit was confirmed
The recent availability of new effective agents to treat metastatic colon cancer is likely to prolong survival duration following recurrence

18. ACCENT: Future plans Update ACCENT based on newer trials
Oxaliplatin: MOSAIC, C-07
Irinotecan: PETACC-3; C89803
Capecitabine: X-ACT
Validate existing model; extend based on new data
Develop interactive calculator to define optimal clinical trial endpoint, based on user defined inputs (e.g. mechanism of action, stage mix, post-recurrence survival)
DFS vs OS; best time point

19. ACCENT Collaborative Group
G Yothers, M O’Connell, N Wolmark, S Wieand– NSABP
J Benedetti, C Blanke – SWOG
R Labianca – Ospedali Riuniti (Italy)
D Haller, P Catalano, A Benson – ECOG
C O’Callaghan – NCIC
JF Seitz – University of the Mediterranean (France)
G Francini – University of Siena (Italy)
A de Gramont, T Andre – GERCOR
R Goldberg – CALGB
M Buyse – IDDI (Belgium)
R Gray, D Kerr – Oxford
D Sargent, A Grothey, E Green, S Alberts - NCCTG