1. Previous medical history C n= 37 CB n= 32 CBM n= 30 Total n= 99 Hypertension23 (62%)16 (50%)16 (53%)55 (56%) Hypercholesterolaemia6 (16%)7 (22%)7 (23%)20 (20%) Diabetes7 (19%)6 (18%)2 (7%)15 (15%) Current smoker1 (3%) 0 (0%)2 (2%) Previous smoker6 (17%)2 (7%)4 (13%)12 (13%) Prior Myocardial infarction3 (8%)4 (13%)3 (10%)10 (10%) Prior Angina pectoris3 (8%)3 (9%)1 (3%)7 (7%) Prior Cerebrovascular accident5 (14%)0 (0%)1 (3%)6 (6%) Prior Transient ischaemic attack2 (5%)1 (3%)2 (7%)5 (5%) Prior peripheral vascular disease1 (3%)0 (0%)1 (3%)2 (2%) C n= 37 CB n= 32 CBM n= 30 Total n= 99 Stratification variables Starting Capecitabine dose 2000mg/m 2 /d32 (86%)28 (88%)27 (90%)87 (88%) 2500mg/m 2 /d5 (14%)4 (13%)3 (10%)12 (12%) ECOG PS 0-134 (92%)28 (88%)25 (83%)87 (88%) General characteristics Age Median Age Years (range) 78.5 (75.2-86.0) 78.7 (75.0-84.9) 80.2 (75.2-83.8) Gender Male26 (70%)24 (75%)16 (53%)66 (67%) Primary tumour site Colon25 (68%)24 (75%)19 (63%)68 (69%) Rectum8 (22%)5 (16%)8 (27%)21 (21%) Other3 (8%)3 (9%)3 (10%)9 (9%) Uncertain1 (3%)0 (0%) 1 (1%) Primary tumour resected29 (78%)28 (88%)24 (80%)81 (82%) Metastases resected5 (14%)2 (6%)2 (7%)9 (9%) Extent of disease Liver31 (84%)22 (69%)23 (77%)76 (77%) Lung14 (38%)18 (56%)12 (40%)44 (44%) Peritoneal/Omental9 (24%)2 (6%)6 (20%)17 (17%) The MAX trial included 21% of patients who were aged >75 years. The frequency of co -morbidities were similar to those reported in the general population of this age. The majority of clinicians did choose the lower dose of capecitabine for those aged >75 years. Significant improvement in PFS with addition of bevacizumab (+/- mitomycin C) to capecitabine was seen in this geriatric population, with similar to results reported when compared to the ITT group and those <75 years (data not shown). There was no impact of age based on the interaction test for OS, RR or PFS. Treatment was well tolerated with no signal of increased toxicity (including VTE/ATE) when compared to those aged <75 years. Geriatric age alone should not preclude consideration of bevacizumab as a treatment option for advanced colorectal cancer Abstract Schema Background Methods Fig 1: Kaplan-Meier curves for PFS >75 years Fig 2: OS age subgroup comparisons with test for interaction Conclusions Geriatric subgroup of AGITG MAX trial. International randomised phase III trial of capecitabine (C), bevacizumab (B) and mitomycin C (M) in 1st line metastatic colorectal cancer (CRC). T. J. Price, D. Zannino, K. Wilson, J. Simes, G. A. Van Hazel, B. A. Robinson, A. Broad, V. Ganju, S. P. Ackland, N. C. Tebbutt. The Queen Elizabeth Hospital, Adelaide, Australia; NHMRC Clinical Trials Centre, Sydney, Australia; Sir Charles Gairdner Hospital, Perth, Australia; Christchurch Hospital, Christchurch, New Zealand; Barwon Health, Geelong, Australia; Frankston Hospital, Melbourne, Australia; Newcastle Mater Misericordiae Hospital, Newcastle, Australia; Austin Health, Melbourne, Australia. On behalf of the Australasian Gastro-Intestinal Trials Group. Background: In an aging population a greater proportion of geriatric patients will be considered for systemic chemotherapy. CRC is a common cancer and will be a major health issue in geriatrics. Methods: MAX, a three arm study of C v CB v CBM, found an improvement in PFS with addition of B (+/- MMC) to C¹. This analysis assesses effect of adding B (+/- MMC) to C on PFS, OS, RR and toxicity in geriatric patients (age >75y). Results: 99 patients (21%) were >75y. Number/Median age: C 37/78.5y (75.2-86), CB 32/78.7y (75.2-84.9), CBM 30/80.2y (75.2-83.4). Baseline characteristics were well balanced. 88% commenced C dose of 2000mg/m 2 /day, d1-14, q21 (61% for 75y v 20% 75y C/CB/CBM respectively was (%); vomiting 5/13/3, diarrhoea 19/22/20, stomatitis 3/0/3, HT 0/3/3, thrombosis/thrombus/embolism 5/6/13, cardiac 0/6 (3 Gd5)/3. There was 1 perforation (Gd5) in C. Grade 2/3 HFS (%) was 38/59/53. One Gd 3-4 neutropenia episode in CB, no Gd 3-4 thrombocytopenia. Overall, toxicity rate similar to <75 y. Conclusion: Significant improvement in PFS with addition of B to C was seen in this geriatric population, similar to results of ITT group and those <75yrs. Treatment was well tolerated with no signal of increased toxicity when compared to those <75yrs, including VTE/ATE. Baseline demographics > 75 years NHMRC Clinical Trials Centre, The University of SydneyAUSTRALASIAN GASTRO-INTESTINAL TRIALS GROUP The MAX study is an investigator initiated study, sponsored by the AGITG. An unrestricted educational grant was provided by Roche Products Australia. Co-morbidity demographics > 75 years Aging involves a progressive decline in functional reserve and increased frequency of co-morbidity/Chronic disease. With age, the frequency of cancer also increases. CRC is one of the most common cancers in the population and thus we have a combination of increased frequency of CRC in older patients at a time when their general health is declining. Patients over 75 years historically were excluded from clinical trials. When included patients over 70 years often make up less than 20% of the total patient group, and subsequently the number of patients over 75 years is relatively small. There is conflicting evidence as to the tolerance and outcome of chemotherapy for patients with CRC defined as elderly. The definition of elderly varies between reports making interpretation of results difficult (eg > 65, >70 and > 75 are frequently defined age groups). For fluoropyrimidines, toxicity differences may relate to method of delivery adding to the difficulty of interpreting results. For capecitabine poor renal function, which declines with age, increases the risk of toxicity With the addition of biological agents new toxicities need to be considered, in particular for bevacizumab, where there appears to be higher rates of thromboembolic disease reported. As the MAX trial included an older population we have undertaken an analysis of the patients who we have defined as elderly or geriatric (age >75 years) to further assess the impact of age on outcome and tolerance. Median PFS (months)95% CI Median OS (months) 95% CI C5.6(4.1 - 6.5)13.4(10.1 - 19.9) CB8.8(5.0 - 9.9)15.7(9.0 - 19.8) CBM10.4(8.8 - 12.0)19.9(13.2 - 23.1) Median progression free survival and overall survival in patients >75 years Response C N= 32 (%) CB N= 30 (%) CBM N= 28 (%) Total* N= 90 (%) CR0000 PR9 (28)7 (23)16 (57)32 (36) SD18 (56)17 (57)10 (36)45 (50) PD5 (16)2 (7)1 (4)8 (9) Unknown0 (0)4 (13)1 (4)5 (6) Response Rate9 (28)7 (23)16 (57)32 (36) Response Rate Results patients age >75 years <75y≥75y Cap n= 119 (%) Bev n= 253 (%) Cap n= 37 (%) Bev n= 62 (%) ToxicityGrade 3-5 Febrile neutropenia3 (2.5)6 (2.4)01 (1.6) Anorexia6 (5.0)9 (3.6)2 (5.4)2 (3.2) Nausea6 (5.0)15 (5.9)3 (8.1)2 (3.2) Vomiting6 (5.0)10 (4.0)2 (5.4)5 (8.1) Diarrhoea10 (8)39 (15)7 (19)13 (21) Stomatitis3 (2.5)7 (2.8)1 (2.7)1 (1.6) Rash: Hand-foot skin reaction/PPE19 (16)68 (27)6 (16)17 (27) Fatigue10 (8.4)27 (10.7)5 (13.5)8 (12.9) Thrombocytopenia07 (2.8)00 Proteinuria1 (0.8)12 (4.7)03 (4.8) Hypertension1 (0.8)14 (5.5)02 (3.2) Thrombosis/thrombus/embolism9 (7.6)24 (9.5)2 (5.4)6 (9.7) Cardiac ischemia/infarction/angina07 (2.8)03 (4.8) CNS cerebrovascular ischemia03 (1.2)01 (1.6) Arterial thromboembolic event010 (4.0)02 (3.2) Haemorrhage3 (2.5)8 (3.2)1 (2.7)2 (3.2) Bowel perforation04 (1.6)1 (2.7)0 HUS/HUS-like syndromes02 (0.8)00 <75yo≥75yo Interaction p HR (95% CI)p p PFSMedian PFS: 7.1mMedian PFS: 7.3m C vs. CB0.65 (0.50 - 0.84)0.0010.52 (0.32 - 0.86)0.010.24 C vs. CBM0.66 (0.51 - 0.86)0.0020.38 (0.23 - 0.64)0.0002 C vs. CB/CBM0.65 (0.52 - 0.82)0.00030.45 (0.29 - 0.69)0.00030.19 PFS– subgroup comparisons with test for interaction Toxicity: 75 years MAX was an international, multi-centre randomised phase II/III study of capecitabine v CB v CBM which showed that there is an improvement in PFS with addition of B (+/- MMC) to Capecitabine (Tebbutt et al. JCO 2010 Jul 1;28(19):3191-8). Eligibility included: histologically confirmed, metastatic colorectal cancer carcinoma (CRC), measurable disease, PS 0-2, adequate organ function, no prior treatment for advanced disease excepting prior adjuvant chemotherapy > 6 months prior to randomisation and informed consent. Toxicity was evaluated using National Cancer Institute Common Toxicity Criteria version 3.0 (NCIC CTCAE v3). Tumour response was evaluated using RECIST (Therasse et al. J Natl Cancer Inst 2000; 92: 205-16). Quality of life (QoL) was assessed using EORTC QLQ C30 and gastric/oesophageal modules. Patients of >75 years of age were analysed separately in this unplanned subgroup analysis, with comparison to those aged less than 75 undertaken. This analysis primarily assesses the effect of adding B (+/- MMC) to C on PFS, OS, RR and toxicity in a geriatric set of patients (age >75y). Test for interaction of age group was performed. 0.400.600.801.201.401.60 0.79 (0.50, 1.24), p=0.31 CB/CBM vs. C 0.99 (0.77, 1.27), p=0.94 0.78 (0.46, 1.34), p=0.36 CBM vs. C 1.09 (0.82, 1.45), p=0.55 0.80 (0.47, 1.36), p=0.41 CB vs. C 0.90 (0.67, 1.20), p=0.47 1.00 HR (95% CI) 0.29 0.16 Interaction p HR Cap alone betterWith Bev better < 75yo ≥ 75yo < 75yo ≥ 75yo < 75yo ≥ 75yo