Comparative Effectiveness Research

1. Comparative Effectiveness of Chemotherapy
Regimens for Advanced Lung Cancer
Nikki Carroll
Institute for Health Research
Kaiser Permanente Colorado
HMO Research Network Conference
May 2, 2012

2. REACT Project
• Part of NCI funded Cancer Research Network (CRN) and
Dana Farber Cancer Institute collaboration
• Project Title
• Building CER capacity: Aligning CRN, CMS, and State Resources
to Map Cancer Care
• Goal
• To conduct Research on the Effectiveness of Advanced Cancer
Treatment (REACT)

3. Project Team
• KPCO • Dana Farber Cancer
• Deb Ritzwoller, Tom Delate, Institute
Jared Freml, Kim Bischoff, Nikki • Jane Weeks, Deb Schrag
Carroll
• GHC
• KPNC • Elizabeth Loggers, Arvind
• Larry Kushi, Karl Huang, Ramaprasan, Nick
Heather Clancy Vanneman
• KPNW
• Mark Hornbrook, Joanna
Bulkley, Stephen Houston

4. Background
• Platinum-based chemotherapy may prolong survival and improve
symptom control in advanced stage Non Small Cell Lung Cancer
(NSCLC) patients
• Newer agents including biologics and targeted agents used as
singlet, doublet, or triplet regimens may improve survival
• Newer agents are expensive and may produce side effects
requiring hospitalization.
• Little is known about the comparative effectiveness of various
regimens in an HMO-based community setting

5. Aim of Study
• Examine comparative effectiveness of patients
with late stage NSCLC in terms of
• Survival
• Number of hospitalizations
• Total hospital days

6. Study Design and Sample
• Retrospective cohort identified at 4 HMOs
• Inclusion Criteria
• Stage IIIB/IV NSCLC diagnosis in Tumor Registry
• First cancer diagnosis
• Diagnosed 2000 through 2007
• 21 years or greater at diagnosis
• Continuous enrollment from diagnosis until death,
disenrollment or end of study (December 2008)
• Survival at least 1 month post diagnosis
• Patients not on concurrent therapy

7. Methods
• Survival Analysis
• Stabilized inverse probability weighted estimators
• Propensity covariates: age group, gender, race, median family
income, stage at diagnosis, tumor grade, year of diagnosis, modified
Charlson comorbidity score and health plan
• Number of Hospitalizations/Hospital Days
• Poisson regression modeling
• Stabilized inverse probability weighted estimators
• Propensity covariates: age group, gender, race, median family
income, stage at diagnosis, tumor grade, year of diagnosis, modified
Charlson comorbidity score, and health plan

8. Results
Proportion of Stage IIIB/IV NSCLC Patients Receiving Chemotherapy (N = 6614)
Patients
receiving Doublet
Patients not chemo within Regimen
receiving 120 days 77%
chemo within 55% Singlet
120 days Regimen
N = 3,072
45% 18%
Triplet
Regimen
5%

9. Results by Age Category
• 3,072 patients receiving chemo identified
6% 4%
100%
80%
60%
73%
79%
40%
20%
23%
0% 15%
< 65 > 65
Singlet Doublet Triplet/Oth

10. Results
Year of Diagnosis
100%
90%
80%
70%
60%
Triplet/Oth
50%
40% Doublet
30% Singlet
20%
10%
0%
2000 2001 2002 2003 2004 2005 2006 2007

11. Results
Distribution of First Line Therapy N (% of Total)
Single Agent Therapy 638 (18.5)
Platinum (Cisplatin / Carboplatin) 182 (5.3)
Taxanes 55 (1.6)
Erlotinib 153 (4.4)
Other Singlet 248 (7.2)
Doublet Therapy 2660 (77.0)
Platinums + Taxanes 1930 (55.8)
Platinums + Gemcitabine 268 (7.8)
Platinums + Other 410 (11.9)
Other Doublets 52 (1.5)
Triplet Therapy 160 (4.6)
Carboplatin + Paclitaxel + Bevacizumab 103 (3.0)
Others 57 (1.6)

12. Unadjusted Survival Results
Singlet Doublet Triplet/Other
Mean Survival Time (SE) [Days] 339 (18.1) 466 (13.5) 650 (69.5)
Median Survival Time [Days] 176 252 354
Percent Censored 8.5% 10.4% 29.7%

13. Adjusted Hazard Ratios
HR 95% CI P-value Referent
Group
Singlet vs Triplet/Oth 1.78 1.44 – 2.20 < .0001 Triplet
Doublet vs Triplet/Oth 1.43 1.17 – 1.75 0.0005 Triplet
Singlet vs Doublet 1.29 1.17 – 1.41 < .0001 Doublet

14. Adjusted Survival Curves
Type of Regimen
Singlet
Doublet
Triplet/Oth

15. Adjusted Results
Number of Hospitalizations
Rate Ratio 95% CI P-value Referent
Group
Singlet vs Triplet/Oth 1.42 1.05 – 1.92 0.0229 Triplet
Doublet vs Triplet/Oth 1.12 0.84 – 1.49 0.4430 Triplet
Singlet vs Doublet 1.25 1.09 – 1.43 0.0013 Doublet

16. Adjusted Results
Number of Hospital Days
Rate Ratio 95% CI P-value Referent
Group
Singlet vs Triplet/Oth 1.98 1.71 – 2.29 < .0001 Triplet
Doublet vs Triplet/Oth 1.48 1.29 – 1.71 < .0001 Triplet
Singlet vs Doublet 1.32 1.24 – 1.40 < .0001 Doublet

17. Findings that inform future studies…
100
90
80
Any Chemo +
70
Bevacizumab
60
Doublet/Triplet
50
40 Erlotinib
30
20 Singlet
10
0
2000 2001 2002 2003 2004 2005 2006 2007

18. Conclusions
• Adjusted analysis confirmed that:
• patients on triplet therapy were associated with longer survival than
those patients on singlet or doublet therapy
• patients on triplet therapy were associated with fewer
hospitalizations then those patients on singlet or doublet therapy
• patients on triplet therapy were associated with fewer hospital days
then those patients on singlet or doublet therapy
• Secular changes in the distribution of singlet and triplet
regimens may have an impact on future findings

19. Next Steps
• Additional comparative effectiveness studies
• Examine the factors associated with use of erlotinib and
bevacizumab
• Conduct separate comparative effectiveness analyses
on the impact on survival and hospitalizations by
• Receipt of erlotinib
• Receipt of carboplatin and paclitaxel with and without
bevacizumab

20. Questions?