Adjuvant therapy in older adults: controversies and challenges - Colorectal cancer -

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1 International Society of Geriatric Oncology Lisbon October 23 rd 25t h 2014 Adjuvant therapy in older adults: controversies and challenges - Colorectal cancer - Claus-Henning Köhne Klinik für Onkologie und Hämatologie Oldenburg, Germany

2 The facts for all (?) patients

3 5 FU Increases Cure Rate in Stage III colon cancer patients Evidence in 13,793 Patients with Stage III 10.3% Moertel et al NEJM 1990 Sargent D, J Clin Oncol 2009

4 Stage III X-ACT: Overall Survival Capecitabine vs. 5-FU/FA year Capecitabine (n=1004) 81.3% 5-FU/LV (n=983) 77.6% Estimated probability Cape 2500mg/m² d1-14 Dose modifications in ~60% of patients Years HR = 0.84 (95% CI: ) p=0.07 Twelves et al. NEJM 2005

5 MOSAIK Study Survival: Stage III infusional 5-FU/FA vs. FOLFOX p=0.029 Probability HR [95% CI] 4.4% Stage III 0.80 [ ] FOLFOX4 stage III LV5FU2 stage III Data cut-off: January Overall survival (months) De Gramont et al. ASCO 2007

6 Patient groups in adjuvant Therapy No benefit cured Cured by surgery already T O X I C I T Y Jahre

7 The achievements: Adjuvant chemotherapy for stage III colon cancer S u r v i v a l Years FOLFOX + 4% (Cape? + 3%) FU/FA +15% Total ~ 20%

8 Stage II Small survival benefit (3%) with 5-FU Gray et al. Lancet 2007 No further improvement with FOLFOX Tournigant et al. JCO 2012 No clinically defined high risk group seems to benefit from FU/FA or FOLFOX O Connor et al. JCO 2011

9 Colorectal Cancer: A disease of the elderly Median age of patients in clinical trials ~ 60 years Median age at diagnosis of CRC ~ 70 years 76% > age 65 40% > age 75 12% age > 85 40% of CRCs are stage III at diagnosis Howlander, SEER Cancer Statistics Review, 2011

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11 Additional Expected Years of Life By Age/Gender Life expectancy 75 y: yrs 85 y: 6-7 yrs women men Köhne, Folprecht, Goldberg et al, Oncologist, 13:390, 2008

12 Colon Cancer Stage II vs Stage III Patterns of Recurrence Recurrence Rate , ,7 9,4 4 7,7 3,3 5,6 2,4 4,5 1,9 3,3 1,7 3,1 1,9 1,5 1,3 1,2 1,1 1,3 1,1 0,6 0,7 0,8 0,8 0,5 0,5 0,6 0,3 0,2 0,3 0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 5 5,5 6 6,5 7 7,5 8 Year Stage 2: 67% of recurrences occur by 3 years Stage 2 Stage 3 Stage 3: 75% of recurrences occur by 3 years Sargent et al, JCO 2005

13 US Cancer Demographics and Cancer Trial Enrollment DEMOGRAPHICS (N=75215) ENROLLMENT SEER Incident Cancer Cases % Cancer Trial Participants % Enrollment Fraction* OR enrollment 95% CI RACE White 83% 85.6% 1.7% 1 Black 11% 9% 1.3% 0.71, Hispanic 4% 3% 1.3% 0.72, AGE % 68% 3% % 24% 1.3% 0.43, % 8% 0.5% 0.15, Murthy et al, JAMA 2004; 291: 2720 * enrollment fraction: number of trial enrollees divided by the estimated US cancer cases in each sub- group.

14 California Cancer Registry ( ) Colon Cancer N = Adeno-Ca, age Years T1-4, stage III Post colectomy Known chemotherapy status N = y (44%) N = Age group 12 nodes examined Percentage of patients treated with chemotherapy y N = % y N = % y N = % N = % P - value 58% 51% 50% 48% <.0001 CTx received 74% 62% 38% 11% <.0001 CTx refused 1.8% 3.6% 12% 31% <.0001 Abraham et al. Cancer 2013

15 Elderly patients Treatment with FU plus LV or levamisol n= 3351 (15% > 70y) 7 trials Sargent et al. NEJM 2001

16 All stages Elderly patients and FU/FA vs. FOLFOX MOSAIK data Stage II and III Hazard ratio (95% CIs)* 5y DFS p-value 6y OS p-value <70 years (n=1931) years (n=315) (14%) *Values <1 favor oxaliplatin-based therapy vs. 5-FU/LV; Data for o Tournigand et al. JCO 2012

17 Elderly patients ACCENT analysis stage II and III DFS OS *Values <1 favor oxaliplatin-based therapy vs. 5-FU/LV; Data for oxaliplatin-based regimens 4. McCleary et al. ASCO 2009 (poster 4010) McCleary et al. JCO 2013

18 Stage IIIC (4+LN) in Elderly Patients MOSAIK Sub(sub) group alive probability LV5FU2 DFS FOLFOX4 DFS LV5FU2 OS FOLFOX4 OS OS 18% N= DFS 17% months

19 Adjuvant! Online Prediction for stage II colon cancer: Cancer and non-cancer related 5-year-Mortality Inprovement of cancer specific survival by 1.7% (FU) and 2.3% (FOLFOX) T3 NO MO T4 NO MO T3 cancer death T3 death other cause T4 cancer death T4death other cuase Assumption of Gill model

20 Perioperative therapy of rectal cancer in the elderly Pre-operative CTx/RTx Potential benefit for elderly - reduces local reccurrence + - may preserve sphincter function + - less toxic than post operative RTx/CTx + Pre-operative short course RTx - reduces local recurrence + - less toxic than CTx+RTx ++

21 Conclusions Therapy < 70y > 70y fit elderly Unfit /frail elderly Stage III 5FU/LV or Cape? FOLFOX FOLFOX for N2 +? Stage II 5FU/LV or Cape? - Low risk No adj CTx 5-FU/LV or Cape? - High risk 5FU/LV or Cape? No chemo No data on unfit or frail elderly The decision for adjuvant therapy has to balances the risk of cancer and other competing risks

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