Real-world experience

Technology-enabled real-world evidence (RWE) can now complement clinical trials to provide the full picture of patient outcomes1

RCT
RWE

real-world-experience

ASCO = American Society of Clinical Oncology; FDA = Food and Drug Administration; RCT = randomised controlled trial; RWD = real-world data; RWE = real-world evidence.

RWE is based on data from patients under real-world conditions, offering a patient-centred approach1

real-world-experience

EHR = electronic health record; EMA = European Medicines Agency; FDA = Food and Drug Administration; RWD = real-world data; RWE = real-world evidence.

The combination of data from both RCTs and RWE offers mutually complementary information1

RCT

RCT = randomised controlled trial; RWE = real-world evidence.

RWE can be used to gather data in patients excluded from or unable to be evaluated in RCTs3,5,10

RWE

RWE studies can: 

rwd_vs_rwe5_ire_

RCT= randomised controlled trial; RWE= real-world evidence.

 

 

 

References
  1. Seyfert-Margolis V. Nat Biotechnol. 2018;36(3):228-232.
  2. Maissenhaelter BE, et al. Onkologie (Berl). 2018;24(Suppl 2):91-98.
  3. Beaulieu-Jones BK, et al. Review Clin Pharmacol Ther. 2020;107(4):843-852.
  4. U.S FDA approves Ibrance® (palbociclib) for the treatment of men with HR+, HER2- metastatic breast cancer. Available at: https://www.pfizer.com/news/press-release/press-release-detail/u_s_fda_approves_ibrance_palbociclib_for_the_treatment_of_men_with_hr_her2_metastatic_breast_cancer. Accessed March 2022.
  5. Blonde L, et al.  Adv Ther. 2018;35:1763-1774.
  6. Visvanathan K, et al. J Clin Oncol. 2017;35(16):1845-1854.
  7. ASCO CancerLinQ. Available at: https://www.cancerlinq.org/. Accessed March 2022.
  8. US Food and Drug Administration. Real-world evidence. Available at: https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence. Accessed March 2022.
  9. Cave A, et al. Clin Pharmacol Ther. 2019;106:36-39.
  10. Webster J, Smith D. Clin Ther. 2019;41:336-349.
  11. Kim HS, et al. J Korean Med Sci. 2018;33(34):e213.
  12. Zuidgeest MGP, et al. J Clin Epidemiol. 2017;88:7-13.


©2020 Pfizer. All rights reserved. PP-IBR-IRL-0501 Date of Preparation: March 2022 Legal Category: S1A

PALOMA was the first clinical trial programme to investigate how a CDK4/6 inhibitor might benefit women with HR+/HER2-ABCand is now also the first to be supported by RWE2

real-world-experience

ABC = advanced breast cancer; CDK = cyclin-dependent kinase; EMA = European Medicines Agency; ET = endocrine therapy; FDA = Food and Drug Administration; HR+/HER2- = hormone receptor-positive, human epidermal growth factor receptor 2-negative; mBC = metastatic breast cancer; 
RCT = randomised controlled trial; RWE = real-world evidence.

IBRANCE has been evaluated in 3 RCTs in ~1300 women with HR+/HER2- advanced or mBC as part of Pfizer’s robust PALOMA Clinical Trial Programme3-5

phases

ABC = advanced breast cancer; ER+/HER2- = estrogen receptor-positive, human epidermal growth factor receptor 2-negative; ET = endocrine therapy; HR+/HER2- = hormone receptor positive, human epidermal growth factor receptor 2-negative; mBC = metastatic breast cancer; RCT = randomised controlled trial.

Multiple ongoing real-world studies at varied geographic locations12-16

EHR = electronic health record; PRO = patient-reported outcome; RWE = real-world evidence.

References

  1. McCain J. P T. 2015;40(8):511-520.
  2. DeMichele A, et al. Breast Cancer Res 2021;23:37.
  3. Finn RS, et al. Lancet Oncol. 2015;16(1):25-35.
  4. Finn RS, et al. N Engl J Med. 2016;375(20):1925-1936.
  5. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.
  6. Clinical trials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT00721409. Accessed March 2022.
  7. Clinical trials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT01740427. Accessed March 2022.
  8. Clinical trials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT01942135. Accessed March 2022.
  9. Palbociclib(IBRANCE) US Food and Drug Administration. Resources for Information. Approved drugs. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/palbociclib-ibrance. Accessed March 2022.
  10. European Medicines Agency (EMEA). IBRANCE (palbociclib). Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/ibrance. Accessed March 2022.
  11. IBRANCE (Palbociclib) Capsules FDA Supplement approval. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2019/207103Orig1s008ltr.pdf. Accessed March 2022.
  12. Blum JL, et al. Ann Oncol. 2018;29 (suppl_8):viii90-viii121.
  13. Harbeck N, et al. ESMO Breast 2019; poster 165P.
  14. Kim HS, et al. J Korean Med Sci. 2018;33(34):e213.
  15. Richardson D, et al. ASCO 2020; abstract.


©2020 Pfizer. All rights reserved. PP-IBR-IRL-0501 Date of Preparation: March 2022 Legal Category: S1A

P-REALITY X (Palbociclib Real-world first-Line comparative effectiveness study extended)

A retrospective observational cohort study. A large comparative effectiveness study of 2,888 HR+/HER2- metastatic breast cancer (MBC) patients using electronic health records (EHR) from the Flatiron Database.

The study, which was the largest MBC real-world study to date, looked at post-menopausal women with HR+, HER2- mBC treated in routine clinical practice in the United States. Patients treated with Palbociclib (IBRANCE) in combination with an aromatase inhibitor (AI) compared to AI alone demonstrated an associated significant improvement in overall survival (OS)2

EHR = electronic health record AI = aromatase inhibitor; HR+/HER2- = hormone receptor-positive, human epidermal growth factor receptor 2-negative; mBC = metastatic breast cancer.
 


Authors: Hope S. Rugo, Adam Brufsky, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Rachel M. Layman, Massimo Cristofanilli, Mylin A. Torres, Giuseppe Curigliano, Richard S. Finn, Angela DeMichele.

Please refer to the SmPC before prescribing IBRANCE. Please click here to be directed to the SmPC.
 


 

2,888 HR+/HER2- MBC patients aged ≥18 years who started first-line palbociclib + AI or AI therapy from February 3, 2015, to March 31, 2020. Median follow-up was 23.9 months in the palbociclib + AI group and 24.5 months in the AI group.

 

inclusion_exclusion

 

  • Number of patients (N=2888): PAL+AI (n=1324); AI (n=1564)2
  • Primary endpoint: OS2
  • Secondary endpoint: rwPFS2
     
Observational retrospective analyses are not intended for direct comparisons with clinical trials.
Observational retrospective analyses are designed to evaluate associations among variables and cannot establish causality.


AI = aromatase inhibitor; CDK = cyclin-dependent kinase; EHR = electronic health record; HR+/HER2- = hormone receptor-positive, human epidermal growth factor receptor 2-negative; mBC = metastatic breast cancer 



The P-REALITY X population studied included a diverse group of HR+/HER2- mBC patients

 

Overall, the median age of patients was 70.0 years, 34.8% had de novo MBC, 29.4% had lung or liver involvement, and 38.7% had bone-only disease.

 



Baseline characteristics were well balanced in this large and diverse population after sIPTW*
 

diverse_population

 

Included a heterogeneous US population of post-menopausal men and women in terms of age, race, time to metastatic diagnosis, performance status, bone and visceral involvement, comorbidities



*sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts; Visceral disease was defined as metastatic disease in the lung and/or liver; patients could have other sites of metastases.
Rugo H, et al. Poster 169P. Presented at ESMO Breast Cancer Congress, 3–5 May 2022, Berlin, Germany.

 

Statistical analyses

  • Unadjusted analyses were conducted first.
  • sIPTW as the primary analysis was performed to balance baseline demographic and clinical characteristics.
  • 1:1 PSM was conducted as sensitivity analysis.
  • Median survival times and 95% CIs for OS and rwPFS were estimated using the weighted Kaplan-Meier method.
  • Cox proportional hazards model was used to compute the HR and the corresponding 95% CI.


 

RESULTS

IBRANCE plus AI significantly prolongs real-world overall survival compared with AI alone 

Real-world OS:* sIPTW adjusted analysis

 

adjusted_analysis


Figure adapted from Rugo H, et al. 2022. 
*OS was defined as time in months from start of IBRANCE plus AI or AI alone to death due to any cause recorded by Flatiron Health Analytic Database in the data extract. Date of death was derived from a recent mortality data set generated by combining multiple data sources and benchmarked against the National Death Index. If patients did not die, they were censored at the study cut-off date; sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts.
Rugo H, et al. Poster 169P. Presented at ESMO Breast Cancer Congress, 3–5 May 2022, Berlin, Germany.

 

First-line IBRANCE plus an AI significantly improves real-world overall survival compared to AI alone*†2

Real-world OS in unadjusted cohort and after sIPTW and PSM adjustment

 

sensitivity_analysis_os


Figures adapted from Rugo H, et al. 2022.2 

*before and after sIPTW and PSM adjustment. sIPTW was the primary statistical analysis and PSM was the sensitivity analysis.

Real-world OS was defined as time in months from start of IBRANCE plus AI or AI alone to death due to any cause recorded by Flatiron Health Analytic Database in the data extract. Date of death was derived from a recent mortality data set generated by multiple data sources and benchmarked against the National Death Index. If patients did not die, they were censored at the study cut-off date; sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts;2 §PSM can be used to minimise bias in real-world studies by matching patients across treatment groups, to ensure patient characteristics are balanced;4 sIPTW adjusted analysis.

 

IBRANCE plus AI improves real-world overall survival versus AI alone in the majority of subgroups (1/2)*,†

majority_of_subgroups


Figure adapted from Rugo H, et al. 2022.
*sIPTW adjusted analysis. sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts; Small patient numbers can be a limitation of subgroup analyses. These analyses are considered exploratory. No adjustments were made for multiple testing. 

 

IBRANCE plus AI improves real-world overall survival versus AI alone in the majority of subgroups (2/2)*,†

majority_of_subgroups-2


Figure adapted from Rugo H, et al. 2022.
*sIPTW adjusted analysis. sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts; Small patient numbers can be a limitation of subgroup analyses. These analyses are considered exploratory. No adjustments were made for multiple testing.

 

IBRANCE plus AI significantly prolongs real-world progression-free survival compared with AI alone

Real-world PFS:* sIPTW adjusted analysis

 

adjusted_analysis


Figure adapted from Rugo H, et al. 2022.
*Real-world PFS was defined as the number of months from start of IBRANCE plus AI or AI alone to death or disease progression (concluded by the treating clinician based on radiology, laboratory evidence, pathology, or clinical assessment). If patients did not die or have disease progression, they were censored at the date of initiation of next line of therapy for those with two or more lines of therapy or their last visit during the study period for patients with only one line of therapy; sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts.

 

IBRANCE plus AI significantly prolongs real-world progression-free survival* compared with AI alone2

Real-world PFS in unadjusted cohort and after sIPTW and PSM adjustment 

 

sensitivity_analysis


*Real-world PFS was defined as the number of months from start of IBRANCE plus AI or AI alone to death or disease progression (concluded by the treating clinician based on radiology, laboratory evidence, pathology, or clinical assessment). If patients did not die or have disease progression, they were censored at the date of initiation of next line of therapy for those with two or more lines of therapy or their last visit during the study period for patients with only one line of therapy; sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts;4 PSM can be used to minimise bias in real-world studies by matching patients across treatment groups, to ensure patient characteristics are balanced.4
 

Real-world data complements clinical trial data to provide a more complete picture of patient outcomes2,5

PALOMA-2 PFS5
paloma_pfs
P-REALITY X real-world PFS*,†2
real_world_pfs

Observational retrospective analyses are designed to evaluate associations among variables and cannot establish causality. Observational retrospective analyses are not intended for direct comparison with clinical trials.

*Real-world PFS was defined as the number of months from start of IBRANCE plus AI or AI alone to death or disease progression (concluded by the treating clinician based on radiology, laboratory evidence, pathology, or clinical assessment). If patients did not die or have disease progression, they were censored at the date of initiation of next line of therapy for those with two or more lines of therapy or their last visit during the study period for patients with only one line of therapy; sIPTW was applied to patients to balance baseline demographic and clinical characteristics and to adjust for differences in observed potential confounders between the two cohorts.

 

P-REALITY X supports the use of first-line IBRANCE plus AI as a standard of care for patients with HR+ HER2– mBC

First-line IBRANCE in combination with AI improves both real-world OS and real-world PFS compared to AI alone, including in various patient subgroups

 

significant_improvement
 

P-REALITY X is the largest real-world comparative effectiveness study for IBRANCE to date§ with over 5 years of patient data collected with a comparator control arm


Observational retrospective analyses are designed to evaluate associations among variables and cannot establish causality. Observational retrospective analyses are not intended for direct comparison with clinical trials.

*sIPTW adjusted analysis; 49.1 months for IBRANCE plus AI (n=1572) vs 43.2 months for AI alone (n=1137). Hazard ratio=0.76 [95% CI: 0.68–0.87], p=0.0001; 19.3 months for IBRANCE plus AI (n=1572) vs 13.9 months (n=1137) for AI alone Hazard ratio=0.70 [95% CI: 0.62–0.78], p<0.0001; §As of May 2022. 

 

LIMITATIONS

  • This study is a retrospective database study of electronic health records, which may have missing or erroneous data entry and cannot determine causal relationship.
  • Disease progression was based on the treating physician’s clinical assessment or interpretation of radiographic or pathologic results rather than standard criteria (eg, Response Evaluation Criteria in Solid Tumors).
  • While sIPTW and PSM were used to balance baseline and clinical patient characteristics, unobserved variables cannot be fully addressed through these methods.
  • Some subgroups analyzed may not have sufficient power due to sample size (eg, younger patients aged <50 years.
  • Findings presented here may not be generalisable to patient populations not represented in the Flatiron Database.
  • Safety data not collected as part of the study.

 

AI, aromatase inhibitor; CI, confidence interval; HR, hazard ratio; OS, overall survival; sIPTW, stabilised inverse probability of treatment weighting; mBC, metastatic breast cancer; PSM=propensity score matching; rwPFS=real-world progression-free survival; NE, not estimated; Dx, diagnosis; ECOG PS, Eastern Cooperative Oncology Group performance status; ND, not determined; PFS, progression-free survival; HER2, human epidermal growth factor receptor 2; HR, hormone receptor.

References

  1. IBRANCE® Summary of Product Characteristics.
  2. Rugo H, et al. Poster 169P. Presented at ESMO Breast Cancer Congress, 3-5 May 2022, Berlin, Germany.
  3. Data on File (153). Pfizer.
  4. Austin PC. Multivariate BehavRes 2011;46:399–424.
  5. Rugo HS, et al. Breast Cancer Res Treat 2019;174:719–729.


©2020 Pfizer. All rights reserved. PP-IBR-IRL-0525 Date of Preparation: June 2022 Legal Category: S1A