Lung Cancer in Older Adults.. Appropriate treatment?

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Dr Christopher Steer Border Medical Oncology Albury-Wodonga

Honoraria/ Consulting/ Funded Royalties/ Stock Other Company Name

(please specify) Position Janssen X Gilead X Amgen X Travel

1 Lung Cancer in Older Adults.. Appropriate treatment? Faculty Disclosure X No, nothing to disclose Yes, please specify: Dr Christopher Steer Border Medical Oncology Albury-Wodonga Inaugural Chair Geriatric Oncology Interest Group (COSA) Ownership/ Honoraria/ Consulting/ Funded Royalties/ Stock Other Company Name Equity Employee Expenses Advisory Board Research Patent Options (please specify) Position Janssen X Gilead X Amgen X Travel espenses Lung cancer in a global context Lung Cancer Stats - Australia 2010 AIHW & AACR Cancer in Australia: an overview, Cancer series no. 60. Cat. no. CAN 56. Canberra: AIHW. Lung Cancer Stats - Singapore What is the definition of Elderly? Depends on your point of view

In solid tumour trials Elderly = Age > 70

word Blunderbuss is of Dutch origin, from

combination of donder, meaning "thunder",

2 Definition of Elderly? ELVIS trial something vs nothing. In solid tumour trials Elderly = Age > 70 years. Generally accepted in solid tumours elderly = >70 years Elvis Trial something vs nothing. Chemotherapy The Blunderbuss approach The word Blunderbuss is of Dutch origin, from the Dutch word donderbus, which is a combination of donder, meaning "thunder", and bus, meaning "Pipe" (Middle Dutch: busse, box, tube, from the late latin buxis meaning box ) from Ancient Greek pyxίs (πυξίς), box: esp. from boxwood. Chemotherapy The Blunderbuss approach Cancer in the Older Adult Lung Cancer 2

3 Cancer in the Older Person Individualised management + Targeted therapy? Individualised Oncologic and Geriatric Care Plan EGFR mutation status in Asian patients Cancer in the Older Adult Lung Cancer EGFR mutation status in Asian patients EGFR mutation status in Asian patients 3

4 Cancer in the Older Person Individualised management Individual EGFR mutations in Asian patients +? Individualised Oncologic and Geriatric Care Plan NCCN Guidelines

5 NCCN Senior Adult Guidelines ASCO guidelines

Cancer in the Older Person Individualised management +?

Appropriate treatment taking into account not just the age and/or PS of the patient but also Characteristics of the

Physical limitations Carers/social supports Polypharmacy Nutritional status Cancer in the Older Person Individualised

6 Cancer in the Older Person Individualised management +? Individualised Oncologic and Geriatric Care Plan Cancer in the Older Person Individualised management 1. Assessment 2. Appropriate treatment taking into account not just the age and/or PS of the patient but also Characteristics of the tumour including EGFR and ALK status Comorbidities or the lack of them... mental status, functional status, frailty. Physical limitations Carers/social supports Polypharmacy Nutritional status Cancer in the Older Person Individualised management Appropriate treatment? Avoiding overtreatment and subsequent increased toxicity Avoiding undertreatment Appropriate treatment? Avoid Undertreatment Avoid overtreatment Age > 66 years

7 Lung Cancer in Older Adults First Line Chemotherapy Lung Cancer in Older Adults Second Line Chemotherapy n= 2026 ( 9.5%) First Avoid Undertreatment Avoid Undertreatment 7

8 Avoid Undertreatment #2 Avoid Undertreatment Age > 66 years

9 9

10 IFCT-0501 OS curves IFCT-0501 PFS curves QOL Data IFCT-0501 Overall Survival; Doublet vs monotherapy 10

Cancer in the Older Person Individualised management Assessing patients using the Rule of Thumb +?

Predicting chemotherapy toxicity in older adults with cancer: A prospective 500 patient multi-center study A. Hurria, K.

CGA The Cancer and Aging Research Group JCO Sept 1, 2011 vol. 29 no.

start a new chemotherapy regimen Pre-chemo Assessment Chemotherapy toxicity NCI CTCAE v3.

11 Cancer in the Older Person Individualised management Assessing patients using the Rule of Thumb +? Individualised Oncologic and Geriatric Care Plan Assessing patients using the CGA. Predicting chemotherapy toxicity in older adults with cancer: A prospective 500 patient multi-center study A. Hurria, K. Togawa, S. G. Mohile, C. Owusu, H. D. Klepin, C. Gross, S. M. Lichtman, V. Katheria, S. Klapper, W. P. Tew?CGA The Cancer and Aging Research Group JCO Sept 1, 2011 vol. 29 no Study Schema Tumor/Treatment Characteristics Eligibility criteria - Age 65 or older - Diagnosis of cancer - To start a new chemotherapy regimen Pre-chemo Assessment Chemotherapy toxicity NCI CTCAE v3.0 (2 MDs) End chemo N Cancer type Sample size: 500 patients 7 participating institutions (Cancer and Aging Research Group) 0 Lung GI Gynecology Breast Urological Other Cancer Stage: 61% stage IV Treatment: 70% polychemotherapy 18% WBC growth factor with cycle 1 11

Age 73 years GI/GU Cancer Standard Dose Poly-chemotherapy Predictors of Toxicity Hemoglobin (male: <11, female: <10) Creatinine Clearance (Jelliffe-ideal wt <34) Fall(s) in last 6 months Hearing

12 Age 73 years GI/GU Cancer Standard Dose Poly-chemotherapy Predictors of Toxicity Hemoglobin (male: <11, female: <10) Creatinine Clearance (Jelliffe-ideal wt <34) Fall(s) in last 6 months Hearing impairment (fair or worse) Limited in walking 1 block (MOS) Assistance required in medication intake (IADL) Decreased social activity (MOS) Age Tumor/ Treatment Variables Labs Geriatric Assessment Variables Predictive Model II Risk factors for Gr. 3-5 Toxicity OR (95% CI) Score Age 73 yrs 1.8 ( ) 2 GI/GU cancer 2.2 ( ) 3 Standard dose 2.1 ( ) 3 Poly-chemotherapy 1.8 ( ) 2 Hemoglobin (male: <11, female: <10) 2.2 ( ) 3 Creatinine Clearance (Jelliffe ideal wt) < ( ) 3 1 or more falls in last 6 months 2.3 ( ) 3 Hearing impairment (fair or worse) 1.6 ( ) 2 Limited in walking 1 block (MOS) 1.8 ( ) 2 Assistance required in medication intake 1.4 ( ) 1 Decreased social activity (MOS) 1.3 ( ) 1 Possible score range: 0-25 Model Performance: Prevalence of Toxicity by Score MD-rated KPS vs. Model II ROC: 0.72 Grade 3-5 Toxicities 100% 80% 60% 40% Low 27% (0 to 5) Mid 53% (6 to 11) 45% 63% High 83% ( 12) 76% 92% 20% 31% 21 % 0% 0 to to 8 9 to to N=39 N=64 N=161 N=123 N=50 N=36 Total Score Grade 3-5 Toxicities 100% 80% 60% 40% 20% 0% 100% 80% 60% 40% 20% 0% Low Mid High 62% 50% 51% MD KPS High Mid 83% Low 53% 27% Model II score Chi-square test p=0.17 Chi-square test p<.0001 Retrospective review n = 120 Recruited over 12 months Age > 65 years Scheduled to received chemotherapy 12

Scoring system slightly modified (removed GI/GU item) Scoring system slightly modified (removed GI/GU item) Wide

1 Risk score predicts grade 3-5 toxicity better than KPS Risk score predicts grade 3-5 toxicity better than KPS

Source: Journal of Geriatric Oncology 2013; 4:334-339 (DOI:10.1016/j.jgo.2013.05.

13 Scoring system slightly modified (removed GI/GU item) Scoring system slightly modified (removed GI/GU item) Wide range of chemotherapy regimens used 10% single agent. Fig. 1 Fig. 1 Risk score predicts grade 3-5 toxicity better than KPS Risk score predicts grade 3-5 toxicity better than KPS in this retrospective review.. But how do we use it in practice? What is the cut-off for combination therapy? Source: Journal of Geriatric Oncology 2013; 4: (DOI: /j.jgo ) Copyright 2013 Elsevier Inc. Terms and Conditions Source: Journal of Geriatric Oncology 2013; 4: (DOI: /j.jgo ) Copyright 2013 Elsevier Inc. Terms and Conditions 13

2012;307(15):1593-1601. doi:10.1001/jama.2012.454 Figure Legend: Date

14 From: Carboplatin and Paclitaxel With vs Without Bevacizumab in Older Patients With Advanced Non Small Cell Lung Cancer JAMA. 2012;307(15): doi: /jama Figure Legend: Date of download: 10/20/2013 Copyright 2012 American Medical Association. All rights reserved. 14

15 I-PASS preplanned subgroup analysis Progression free survival 15

16 PFS Curve (n=31) Median PFS = 12.1 months OS at 2 years = 58% 16

17 What is over the horizon? Tackling resistance to 1st Gen EGFR inhibitors presented at ASCO 2014 Tackling resistance to crizotinib in ALK+ tumours presented at ASCO 2014 Source - otinib/ Immunotherapy the long tail effect Examples of PD-L1 NSCLC Sample Immunohistochemical Staininga Clin Cancer Res January 15, ; 336 Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting 17

Percent Change from Baseline in Tumor Size in Evaluable Patientsa (Central Review, RECIST v1.

Meeting Maximum 1) Antitumor Activity by Pembrolizumab Dose Presented By Naiyer Rizvi at 2014 ASCO

Responsea Change From Baseline in Tumor Size in All Evaluable Patientsa (RECIST v1.

18 Response Rate by RECIST v1.1 (Central Review) and by irrc (Investigator-Assessed) with PD-L1 Clinical Trial Assaya Maximum Percent Change from Baseline in Tumor Size in Evaluable Patientsa (Central Review, RECIST v1.1) Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Maximum Percent Change from Baseline in Tumor Size in Evaluable Patientsa (Central Review, RECIST v1.1) Antitumor Activity by Pembrolizumab Dose Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Time to and Durability of Responsea Change From Baseline in Tumor Size in All Evaluable Patientsa (RECIST v1.1 by Central Review) Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting 18

Change From Baseline in Tumor Size in All Evaluable Patientsa (RECIST v1.

Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Conclusions Presented By

together 1. Aim for appropriate treatment 2.

19 Change From Baseline in Tumor Size in All Evaluable Patientsa (RECIST v1.1 by Central Review) Change From Baseline in Tumor Size in Patients With New Lesions (RECIST v1.1 by Central Review) Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Conclusions Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting Conclusions - Let s put it all together 1. Aim for appropriate treatment 2. Can be achieved via adequate assessment and avoidance of ageism. 3. There is developing evidence that older patients can benefit from standard treatments and that undertreatment is detrimental. 19

Conclusions..2 Practical aspects of treating older patients with lung cancer. 1. Doublet chemotherapy should be the standard of care in older patients with lung cancer.

The role of a formal geriatric assessment and the CARG tool for treatment decisions as well as an intervention should be explored further. Conclusions.

Targeted therapies such as EGFR and ALK inhibitors should be used in patients who exhibit the target regardless of age. but watch out for increased toxicities Any Questions?

20 Conclusions..2 Practical aspects of treating older patients with lung cancer. 1. Doublet chemotherapy should be the standard of care in older patients with lung cancer. Single agent chemotherapy should be reserved for patients considered unfit for platinum agents and/or of poor performance status (regardless of age). 2. The role of a formal geriatric assessment and the CARG tool for treatment decisions as well as an intervention should be explored further. Conclusions..3 Practical aspects of treating older patients with lung cancer. 1. Bevacizumab is not routinely recommended for older patients due to lack of efficacy and increased toxicity. 2. Targeted therapies such as EGFR and ALK inhibitors should be used in patients who exhibit the target regardless of age. but watch out for increased toxicities Any Questions? Lung Cancer Lung Cancer Stats - Australia 2010 AIHW & AACR Cancer in Australia: an overview, Cancer series no. 60. Cat. no. CAN 56. Canberra: AIHW. 20

Integrating Geriatrics into Oncology Care

Integrating Geriatrics into Oncology Care William Dale, MD, PhD Chief, Geriatrics & Palliative Medicine Director, Specialized Oncology Care & Research in the Elderly (SOCARE) Clinic University of Chicago