1. Colorectal Cancer in Older Patients Key Issues
Etienne GC Brain, MD PhD Institut Curie
Saint-Cloud, France

2. Epidemiology Screening > 75???
23-45% digestive tumours are diagnosed > 75 yo (FRANCIM 2010)
CRC (INCa 2012)
75-84 yo 14.7% of all cancers
> 85 yo 18.7% of all cancers
1st cancer any sex in elderly
30% new cases yo
Median age at diagnosis 70 yo
Screening > 75???

3. 28 independent studies & 34 194 patients Older patients
Increased frequency of comorbid conditions
More later-stage disease
More emergency surgery
Less curative surgery
More postoperative morbidity and mortality
Worse OS but less striking for CRC-specific survival
Lancet 2000

4. Undertreatment 110 cases > 75 yo (1995-2000)
Treatment according guidelines = 48% pts
Surgery 87% (R0 56%)
Chemotherapy
III 26%
IV 17%
XRT (rectum)
Early stage 17%
Palliative 21%
Apparicio CROH 2009

5. Doat Eur J Cancer 2014

6. 75+ vs < 75: median OS 8.4 months vs 22.3 months
(17.1 months in 75+ w/ chemo)
Doat Eur J Cancer 2014

7. Adjuvant Setting
Sargent NEJM 2001

9. Benefits of oxaliplatin beyond fluoropyrimidine in pts > 70 years is uncertain
Increased risk for AE’s with combination chemo (25% SAE w/ 15% neuropathy)
Decision based on clinician’s clinical judgment
Recurrence risk
Fluoropyrimidine monotherapy is appropriate when oxaliplatin is felt to add excessive risk of toxicity for a patient

10. Questions
Stratification on frailty/life expectancy for oxaliplatin vs none or chemo ves none (ADAGE/PRODIGE 34)
Deficiency in mismatch repair & MSI (high frequency in older patients and improved prognosis)?

11. Metastatic Setting
Most studies show similar benefit to systemic treatments as younger patients
Few specific studies in older patients
FOCUS 2, FFCD, AVEX
Chemo
Mono vs bi-therapy (oxaliplatin, irinotecan)
! Capecitabine > 70
Targeted treatments
Anti-EGFR, anti-VEGF
! Bevacizumab with ATE history

12. A : LV5 FU2 q2w B : FOLFOX q2w Frail and elderly C : capecitabine q3w
PS: FOCUS 1 (Fluorouracil, Oxaliplatin, CPT11 [irinotecan]: Use and Sequencing): median age 64 yo (vs 60% deaths > 75+) (Lancet 2007)
> 6 w: 100% if good tolerance
Initial: 80%
Dose
A : LV5 FU2 q2w R
1:1:1:1
B : FOLFOX q2w
Frail and elderly
C : capecitabine q3w
D : XELOX q3w
Stratification: centre, PS, surgery of primary, age
Primary objective: Overall Treatment Utility = oxaliplatin and PFS (A vs B + C vs D), capecitabine and QoL (A vs C et B vs D)
Secondary objectives: RR, toxicity, OS
Statistics: 2x2, PFS 6 vs 9 mth, α 5% β 20%, QoL 40% vs 60% improvement at 12w, α 5% β 10%, 460 patients

13. Oxaliplatine 5 FU More AE grade ≥ 3 if Multivariate
Median PFS 5.8 [ ] vs 4.5 [ ], HR 0.84 ( , p = 0.07)
More RR 41-54% vs 35-37%)
5 FU
QOL mprovement by 56% w/FU or capecitabine
More AE grade ≥ 3 if
Oxaliplatin 39% vs 32% p = 0.17
Cape 40% vs 30% p = 0.03
Multivariate
Less symptoms
Limited disease
 Better OTU

14. FFCD 2001-02 123 patients with mCRC, first line of chemotherapy
5-FU-based chemo ± irinotecan
Median age 80 yo (75-91)
Charlson index≤ 1 75%
MMSE ≤ 27/30 31%
IADL impairment 34%
Toxicity
grade 3-4 toxicity
71 patients (58%): IRI, MMSE, IADL
Dose-intensity reduction > 33%
41 patients (33%): IRI, Alk phosph
≥ 1 unexpected hospitalization (4 mth)
54 patients (44%): MMSE, GDS
Cognitive function and autonomy impairment should be taken into account when choosing a regimen for chemotherapy
Aparicio J Clin Oncol 2013

16. Cunningham Lancet Oncol 2013

17. AVEX PFS: 9.1 vs 5.1 mos (HR 0.53, p<0.001)
OS: 20.7 vs 16.8 mos (HR 0.79, p=0.182)
[AVF2107g results: IFL+/- BEV 20.3 mos vs 15.6 mos (HR 0.66, p<0.001)]
RR: 19.3% vs 10% p=0.042
Grade 3+ AEs: 59% vs 44.1%
Conclusions: Cape + BEV could be a standard for selected elderly patients
Cunningham Lancet Oncol 2013

18. SEER database
3,039 patients ≥ 66, stage IV breast, lung, colon cancer, , bevacizumab
Contra-indication defined as 2 claims for thrombosis, cardiac disease, stroke, hemorrhage, hemoptysis, or GI perforation
Toxicity defined as 1st development of 1 condition > beva
Beva use associated w/ white race, later year of diagnosis, tumor type, and decreased comorbid conditions
35.5% had contra-indication
Black race, increased age, comorbidity, later year of diagnosis, lower socioeconomic status, lung and CRC
If no contra-indication  30% complication (black race)
Hershman J Clin Oncol 2013

19. Cetuximab Pooled analysis from KRAS wild-type pts
CRYSTAL (FOLFIRI +/- cetuximab)
OPUS (FOLFOX +/- cetuximab)
OS, PFS and safety were all similar among older ( ≥ 70 years) and younger (<70 years) pts.
Grade 3+ toxicity was increased in both treatment arms for elderly patients
NO obvious interaction between age (< 70 vs ≥ 70 years) and the differences for treatment toxicity between the arms.
Folprecht ESMO 2010

20. Treatment decisions should not be based on age alone
Fit older patients can tolerate combination cytotoxic therapy as well and benefit as much as younger patients
Same for biologics
Consider less intense regimens for those who are not candidates for standard regimens
Reduced dose FP + oxaliplatin
Cape + BEV