cancer in older adults….. - international society of geriatric … · 04.01.2016 3 cancer in the...

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Lung Cancer in Older Adults…..

Appropriate treatment?

Dr Christopher SteerBorder Medical Oncology

Albury-WodongaInaugural Chair Geriatric Oncology Interest Group (COSA)

Faculty Disclosure

Company NameHonoraria/Expenses

Consulting/ Advisory Board

Funded Research

Royalties/ Patent

Stock Options

Ownership/ Equity

PositionEmployee

Other (please specify)

Janssen X

Gilead X

Amgen X Travel espenses

No, nothing to disclose X Yes, please specify:

Lung cancer in a global context Lung Cancer Stats - Australia 2010Lung Cancer Stats - Australia 2010

AIHW & AACR 2010. Cancer in Australia: an overview, 2010. Cancer series no. 60. Cat. no. CAN 56. Canberra: AIHW.

Lung Cancer Stats - SingaporeLung Cancer Stats - Singapore

http://www.nccs.com.sg/patientcare/whatiscancer/cancerStatistics/Pages/Home.aspx

What is the definition of

Elderly?

Depends on your point of

view.....

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Definition of “Elderly”?Definition of “Elderly”?

In solid tumour trials – Elderly = Age > 70 years.In solid tumour trials – Elderly = Age > 70 years.

ELVIS trial – something vs nothing.ELVIS trial – something vs nothing.

Generally accepted in solid tumours “elderly” = >70 yearsGenerally accepted in solid tumours “elderly” = >70 years

Elvis Trial – something vs nothing.Elvis Trial – something vs nothing. Chemotherapy – The Blunderbuss approachChemotherapy – 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 approachChemotherapy – The Blunderbuss approach Cancer in the Older Adult – Lung CancerCancer in the Older Adult – Lung Cancer

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Cancer in the Older Person

Individualised managementCancer in the Older Person

Individualised management

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Individualised Oncologic and Geriatric Care Plan

Targeted therapy

EGFR mutation status in Asian patientsEGFR mutation status in Asian patients Cancer in the Older Adult – Lung CancerCancer in the Older Adult – Lung Cancer

EGFR mutation status in Asian patientsEGFR mutation status in Asian patients EGFR mutation status in Asian patientsEGFR mutation status in Asian patients

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Individual EGFR mutations in Asian patients

Individual EGFR mutations in Asian patients




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NCCN Guidelines - 2014NCCN Guidelines - 2014

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NCCN Senior Adult Guidelines - 2013NCCN Senior Adult Guidelines - 2013

ASCO guidelines 2011ASCO guidelines 2011

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Individualised management1. 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

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





• Avoiding overtreatment and subsequent increased toxicity

• Avoiding undertreatment


• Avoiding overtreatment and subsequent increased toxicity

• Avoiding undertreatment

Appropriate treatment?Appropriate treatment?

Avoid “overtreatment”Avoid “overtreatment”

Avoid UndertreatmentAvoid Undertreatment

Age > 66 years1997-2002

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Lung Cancer in Older AdultsLung Cancer in Older AdultsFirst Line Chemotherapy

First

First Line Chemotherapy

First

Lung Cancer in Older AdultsLung Cancer in Older AdultsSecond Line Chemotherapy

n= 2026 ( 9.5%)

Second Line Chemotherapyn= 2026 ( 9.5%)

Avoid UndertreatmentAvoid Undertreatment Avoid UndertreatmentAvoid Undertreatment

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Avoid Undertreatment #2Avoid Undertreatment #2 Avoid UndertreatmentAvoid Undertreatment

Age > 66 years1997-2002

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IFCT-0501 OS curvesIFCT-0501 PFS curves

QOL Data IFCT-0501 –Overall Survival; Doublet vs monotherapy

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Assessing patients using the “Rule of Thumb”Assessing patients using the “Rule of Thumb”

Assessing patients using the CGA.Assessing patients using the CGA.

?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

The Cancer and Aging Research Group

JCO Sept 1, 2011 vol. 29 no. 25 3457-3465

Study Schema

Eligibility criteria

- Age 65 or older

- Diagnosis of cancer

- To start a new chemotherapy regimen

Pre-chemo

AssessmentEnd chemo

Chemotherapy toxicity NCI CTCAE v3.0

(2 MDs)

� Sample size: 500 patients

� 7 participating institutions (Cancer and Aging Research Group)

Tumor/Treatment Characteristics

144 137

86

5650

27

0

20

40

60

80

100

120

140

160

N

Lung GI Gynecology Breast Urological Other

Cancer type

Cancer Stage: 61% stage IVTreatment: 70% polychemotherapy

18% WBC growth factor with cycle 1

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Predictors of Toxicity�Age ≥ 73 years

�GI/GU Cancer

�Standard Dose

�Poly-chemotherapy

�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/TreatmentVariables

Geriatric Assessment

Variables

Labs

Predictive Model IIRisk factors for Gr. 3-5 Toxicity OR (95% CI) Score

Age ≥73 yrs 1.8 (1.2-2.7) 2

GI/GU cancer 2.2 (1.4-3.3) 3

Standard dose 2.1 (1.3-3.5) 3

Poly-chemotherapy 1.8 (1.1-2.7) 2

Hemoglobin (male: <11, female: <10) 2.2 (1.1-4.3) 3

Creatinine Clearance (Jelliffe –ideal wt) <34 2.5 (1.2-5.6) 3

1 or more falls in last 6 months 2.3 (1.3-3.9) 3

Hearing impairment (fair or worse) 1.6 (1.0-2.6) 2

Limited in walking 1 block (MOS) 1.8 (1.1-3.1) 2

Assistance required in medication intake 1.4 (0.6-3.1) 1

Decreased social activity (MOS) 1.3 (0.9-2.0) 1

Possible score range: 0-25

Model Performance:Prevalence of Toxicity by Score

Gra

de

3-5

Toxi

citie

s

Total Score

N=39 N=64 N=123 N=36N=50N=161

0%

20%

40%

60%

80%

100%

0 to 4 5 6 to 8 9 to 11 12 to 13 ≥14

“Low” 27%(0 to 5)

31%21%

“Mid” 53%(6 to 11)

45%

63%

“High” 83%( ≥12)

76%

92%

ROC: 0.72

MD-rated KPS vs. Model II

50% 51%62%

0%

20%

40%

60%

80%

100%

90-100 80 ≤70

“Low” “High”“Mid”

Chi-square test p<.0001

Chi-square test p=0.17

27%

53%

83%

0%

20%

40%

60%

80%

100%

0-5 6-10 11-21

“Low”

“Mid”

“High”

Gra

de

3-5

Toxi

citi

es

Model II score

MD KPS

• Retrospective review

• n = 120

• Recruited over 12 months 2011-12.

• Age > 65 years

• Scheduled to received chemotherapy

• Retrospective review

• n = 120

• Recruited over 12 months 2011-12.

• Age > 65 years

• Scheduled to received chemotherapy

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

• 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.

• Wide range of chemotherapy regimens used

• 10% single agent.

Fig. 1

Source: Journal of Geriatric Oncology 2013; 4:334-339 (DOI:10.1016/j.jgo.2013.05.002 )

Copyright © 2013 Elsevier Inc. Terms and Conditions

Risk score predicts grade 3-5 toxicity better than KPS

Fig. 1

Source: Journal of Geriatric Oncology 2013; 4:334-339 (DOI:10.1016/j.jgo.2013.05.002 )

Copyright © 2013 Elsevier Inc. Terms and Conditions

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?

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Date of download: 10/20/2013Copyright © 2012 American Medical

Association. All rights reserved.

From: Carboplatin and Paclitaxel With vs Without Bevacizumab in Older Patients With Advanced Non–Small Cell Lung Cancer

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

Figure Legend:

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I-PASS preplanned subgroup analysisProgression free survival

I-PASS preplanned subgroup analysisProgression free survival

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Median PFS = 12.1 monthsOS at 2 years = 58%

PFS Curve (n=31)

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What is over the horizon?What is over the horizon? Tackling resistance to 1st Gen EGFR inhibitorsTackling resistance to 1st Gen EGFR inhibitors

presented at ASCO 2014

Tackling resistance to crizotinib in ALK+ tumoursTackling resistance to crizotinib in ALK+ tumours

presented at ASCO 2014

Source -http://cancergrace.org/lung/tag/crizotinib/

Immunotherapy – the “long tail” effect…Immunotherapy – the “long tail” effect…

Clin Cancer Res January 15, 2012 18; 336

Examples of PD-L1 NSCLC Sample Immunohistochemical Staininga

Presented By Naiyer Rizvi at 2014 ASCO Annual Meeting

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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)


Maximum Percent Change from Baseline in Tumor Size in Evaluable Patientsa (Central Review, RECIST v1.1)


Antitumor Activity by Pembrolizumab Dose


Time to and Durability of Responsea


Change From Baseline in Tumor Size in All Evaluable Patientsa (RECIST v1.1 by Central Review)


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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)


Conclusions


Conclusions - Let’s put it all together……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.

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.

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Conclusions…..2Conclusions…..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.


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…..3Conclusions…..3


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


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 CancerLung Cancer

http://www.nccs.com.sg/Publications/CancerInformationBooklets/CancerType/Documents/Lung%20Cancer%20(Eng).pdf

Lung Cancer Stats - Australia 2010Lung Cancer Stats - Australia 2010

AIHW & AACR 2010. Cancer in Australia: an overview, 2010. Cancer series no. 60. Cat. no. CAN 56. Canberra: AIHW.