1. Diagnosis and Treatment of Neuropathy Post Chemotherapy in Three Health Care Systems HCSRN 2019 Conference April 10, 2019
Kaiser Permanente Research

2. Fontes et al. The Breast 2016; Serenty et al 2014
Peripheral neuropathy is a common side effect of neurotoxic chemotherapies
Chemo induced neuropathy affects anywhere from 11 to 80% of patients using select therapies (e.g., taxanes, platinums)
CIPN can:
Occur during or after treatment or both
Be acute or chronic in nature
Prevention and Treatment
No recommend therapies for prevention
Duloxetine; other agents used (gabapentin, tricyclic antidepressants)
Limited evidence regarding how to prevent it, how to effectively treat it, and how patients in real world practice are being assessed and treated.
Sources: Rivera et al 2018; Staff N, et al. Annals Neurology 2017; Hershmann D, et al. JCO 2016;
Fontes et al. The Breast 2016; Serenty et al 2014
April 18, 2019
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3. Chemo-Induced Neuropathy: Patient Perspectives
“Since the chemotherapy, my fingers feel numb, as do my toes. When I get up in the morning, my fingers are all numb. … when I sewed trousers, I could finish the task in 15 min in the past, but now I need an hour to finish it because my fingers feel numb…” (P4, 5 months after chemotherapy completion)
“I don't think my numbness will completely disappear … I have gradually become clumsy. I have to get someone to help me go out. If I could go out on my own, I would be very happy. I would be just like normal people and wouldn't need the family to take care of me, but [I] still need people to help [me] to go out ... [participant weeps] … So I try to think happier thoughts.” (P12, 23 months after chemotherapy completion)
Chan et al. European Journal of Oncology Nursing, 2018
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

4. Factors associated with CIPN Diagnosis3
Clinical Risk Factors
Diabetes, other neuropathic conditions 2
Medications
Platinums, vinca-alkaloids, taxanes, and non-cancer medications (e.g., statins)is. 1
Patient Demo
age, race, obesity
Limitations of current studies: small sample size, lack of
generalizability, inadequate patient follow up
Sources: Rivera et al. 2018; Staff N, et al. 2017; Hershmann D, et al. 2016;
Fontes et al. 2016; Serenty et al. 2014; Bao et al. 2016; Bulls et al 2019
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

5. Study Aims & Team
To examine factors associated with peripheral neuropathy (PN) diagnosis and treatment in a cohort of insured cancer patients in three integrated health systems using real world EHR data
Research Team
KP Washington: Jessica Chubak, Rebecca Ziebell, Laura Ichikawa
HealthPartners: Pam Pawloski, Mary Becker
NCI: Donna Rivera
KP Northern California: Alyce Adams, Lin Ma, Tatjana Kolesvska
Funder
The NCI Cancer Research Network, Rapid Analysis pilot study
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

6. Methods (1)
Setting: 3 geographically diverse health systems (KPNC, KP Washington, HealthPartners)
Data Source: VDW
Study Sample
Inclusions: 1st observed (invasive) cancer diagnosis age ; prescribed neurotoxic chemotherapy within 12 months of diagnosis; enrolled at time of diagnosis, chemotherapy, and 12 months prior to chemotherapy with at least one clinic visit
Exclusions: diagnosis of PN or use of PN study drug in 12 months before chemotherapy start; opted out of research studies
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

7. Methods (2) Outcome Measures Covariates Statistical Analysis
New Dx of Peripheral Neuropathy following chemo start
Newly dispensed PN medication following PN Dx
Covariates
Patient demographics
Tumor characteristics
Class of chemotherapy received
Comorbidities
Use of non-cancer drugs with known neurotoxic risk
Statistical Analysis
Cox PH models
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

8. Characteristics of patients initiating chemotherapies of interest (13,051)
Age
40-49
1938 (15%)
50-59
3740 (29%)
60-69
4363 (33%)
70-79
2424 (19%)
80+
586 (4%)
Sex
Female
8260 (63%)
Male
4791 (37%)
Race
White
9820 (75%)
Black or African American
1015 (8%)
Asian or Pacific Islander
2033 (16%)
All Other/Unknown
173 (1%)
Ethnicity
Hispanic
11647 (89%)
Non-Hispanic
1404 (11%)
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

9. First Chemotherapy Drug Used by Class*
paclitaxel
docetaxel
carboplatin
oxaliplatin
cisplatin 517
29% of patients used a combination of drugs, mainly Taxane and Platinum
* Drugs used by n≤10 patients not shown
Number of patients
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

10. Cumulative Incidence Curve for PN Dx, accounting for competing risk
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

11. Cumulative Incidence Curve for PN Treatment, accounting for competing risk
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

12. Time to PN Diagnosis Post Chemotherapy Start
Adjusted HR
95% CI
p-value
Site
A (ref) B C
1.43
1.69
<0.0001
Age
40-49
50-59
60-69 (ref)
70-79
80+
0.87
1.05
0.88
0.62
Sex
Female (ref)
Male
0.91
0.01
Race
White, non-Hispanic (ref)
Black/AA, non-Hispanic
Hispanic
Asian/PI
Other/Unknown
1.23
1.09
0.92
0.90
0.0002
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

13. Time to PN Diagnosis, cont
Adjusted HR
95% CI
p-value
Seer Stage
Local
Regional (ref)
Distant
Unstaged
0.75
0.95
0.65
<0.0001
Diabetes
yes no
1.14
0.003
Chronic Pain
1.25
Other Comorbidities
1.19
Other Neurotoxic Agents
1.15
0.0008
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

14. Time to PN Diagnosis: Chemotherapy Class
Drug Class
Adjusted HR
95% CI
p-value
platinum only (ref)
<0.0001
No platinum
1.01
platinum+taxane
1.29
platinum+other
0.52
platinum+taxane+other
1.02
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

15. Time to New PN Treatment Post PN Dx
Adjusted HR
95% CI
p-value
Site
A (ref) B C
0.81
0.55
<0.0001
Age
40-49
50-59
60-69 (ref)
70-79
80+
1.10
1.06
0.99
0.90
0.65
Sex
Female (ref)
Male
0.94
0.36
Race
White, non-Hispanic (ref)
Black/AA, non-Hispanic
Hispanic
Asian/PI
Other
1.24
1.13
0.85
1.53
0.004
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

16. Time to PN Treatment, cont
Median Time to Dx (Days)
Adjusted HR
95% CI
p-value
Seer Stage
Local
Regional (ref)
Distant
Unstaged
46 (0-270)
73 (1-288)
32 (0-147)
0 (0-180)
0.96
1.12
0.75
0.14
Seizure Disorder
yes no
26 (0-180)
50 (0-230)
0.39
Chronic Pain
61 (0-270)
41 (0-200)
1.26
<0.0001
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

17. Conclusions Factors associated with elevated risk PN Dx PN Treatment
Combination taxane and platinum treatment compared to platinum only (similar result compared to taxane only)
Health care system
Black/African American race
Age 60-69
Regional tumor
Comorbid: diabetes, chronic pain
Use of other neurotoxic agents
PN Treatment
Health care system
Black/African American race
Comorbid chronic pain
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

18. Strengths and Limitations
Sample size
Data from multiple health systems
Ability to control for multiple clinical risk factors
Limitations
Dx rather than assessment of CIPN
Unmeasured confounders
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

19. Discussion
April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

20. Thank you Alyce.S.Adams@kp.org April 18, 2019
| © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.