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P-REALITY-X: Real-world evaluation of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer
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P-REALITY-X: Real-world evaluation of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer
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T00H14M30S
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https://cadmoreoriginalmedia.blob.core.windows.net/b74e42a6-bbe0-4a22-b052-287c15d06da2/VJBM 2023-0004 P-Reality X V2.mp4?sv=2019-02-02&sr=c&sig=H5u7l1FK%2BS7JXH9wcmRtgrCLrfjar4OQyBAAMKIDTtY%3D&st=2024-11-21T09%3A23%3A20Z&se=2024-11-21T11%3A28%3A20Z&sp=r
Upload Date:
2023-10-24T00:00:00.0000000
Transcript:
Language: EN.
Segment:1 Introduction.
[MUSIC PLAYING]
DR HOPE RUGO: On behalf of myself and my authors, I am pleased to present our paper, "Overall Survival with Palbociclib Plus Aromatase Inhibitor Versus Aromatase Inhibitor Alone in Postmenopausal Women and Men with Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, a Large, Real-world Study in US Clinical Practice," published in NPJ Breast Cancer in 2022.
Segment:2 Background.
DR HOPE RUGO: Breast cancer accounts for nearly one third of all cancers among women. Breast cancer treatment recommendations are subtype specific. Approximately 2/3 of breast cancers are hormone receptor positive and human epidermal growth factor receptor two negative or HR positive/HER2 negative. The National Comprehensive Cancer Network, NCCN, guidelines recommend cyclin-dependent kinase 4/6 inhibitors or CDK4/6 inhibitors in combination with endocrine therapy as first line treatment for postmenopausal women, premenopausal women receiving ovarian ablation or suppression, or men with HR positive, HER2 negative Metastatic Breast Cancer, or MBC.
DR HOPE RUGO: The CDK4/6 inhibitor palbociclib was first approved in the United States in February 2015, in combination with the aromatase inhibitor or AI letrozole as first-line treatment for HR positive, HER2 negative metastatic breast cancer. Approval was expanded to include any AI in 2017. The pivotal phase 3 PALOMA-2 clinical trial demonstrated that patients receiving palbociclib plus letrozole had significantly longer progression-free survival than those receiving letrozole alone.
DR HOPE RUGO: Although clinical trials provide valuable drug effectiveness data, patients are subject to strict eligibility criteria and therefore may not represent most patients treated in routine clinical practice. Consequently, real-world studies are important for understanding effectiveness and in turn, informing treatment decisions for patients treated in clinical practice. Comparative real-world effectiveness studies for palbociclib have been limited. The P-REALITY-X study described here aimed to evaluate overall and real-world progression-free survival associated with palbociclib plus an AI versus an AI alone among patients with HR positive/ HER2 negative MBC.
Segment:3 Methods.
DR HOPE RUGO: P-REALITY-X was a retrospective cohort study that used data from the Flatiron Health Analysis Database, a longitudinal database containing de-identified, structured and unstructured electronic health record data from more than three million US cancer patients. Flatiron has an extensive and rigorous data abstraction and harmonization process to ensure optimal data quality for analyses used for regulatory purposes and in peer-reviewed publications.
DR HOPE RUGO: Included patients were treatment-naive, postmenopausal women and men, 18 years of age or older who were first prescribed palbociclib plus an AI or an AI alone for HR positive/HER2 negative MBC between February 3rd, 2015 and March 31st, 2020. Follow-up extended through September 30th, 2020, death, or the patient's last visit, whichever was first.
DR HOPE RUGO: The primary outcome was overall survival, defined as the number of months from the start of treatment with palbociclib plus an AI or an AI alone until death. The secondary outcome was real-world progression-free survival, defined as the number of months from the start of treatment to the first documentation of real-world progressive disease or death due to any cause, whichever occurred first. Disease progression was assessed by the treating clinician using radiology, laboratory evidence, pathology, or clinical assessment. Median survival times for both endpoints were estimated using the weighted Kaplan-Meier method, and hazard ratios were calculated using weighted Cox proportional hazard models.
DR HOPE RUGO: Endpoints were compared across treatment groups using three statistical methods. The unadjusted analysis simply compared the endpoints without controlling for baseline patient characteristics. The stabilized Inverse Probability Treatment Weighting method, sIPTW, and Propensity Score Matching, PSM, are commonly used statistical approaches for real-world data to control for potential confounding effects due to the lack of study randomization. sIPTW was the primary analysis used, and PSM was the sensitivity analysis.
Segment:4 Results.
DR HOPE RUGO: 2,888 patients were included in the study, of whom 1,324 received palbociclib plus an AI, and 1,564 received an AI alone. In the unadjusted cohort, more patients in the palbociclib group had Eastern Cooperative Oncology Group scores of zero, de novo metastatic breast cancer, lower comorbidity indices, and a higher number of metastatic sites, compared with the AI group alone.
DR HOPE RUGO: Patient demographic and clinical characteristics were generally balanced after both sIPTW and PSM, with most standardized differences for each characteristic being less than 0.1. After sIPTW, median patient age was 70 years in both groups and approximately 1/3 of patients were 75 or older. Approximately 2/3 of patients in each group were white and 9% were black. Approximately 30% of patients in each group had visceral disease. Most patients were treated in community practices, with 8% in each group treated at academic medical centers. Median follow-up duration after sIPTW was 23.9 months in the palbociclib group and 24.5 months in the AI-alone group.
DR HOPE RUGO: Median overall survival and real-world progression-free survival was longer in the palbociclib group, compared with the AI-alone group across the unadjusted sIPTW and PSM analyses. After sIPTW, median overall survival was 49.1 months in the palbociclib group, compared with 43.2 months in the AI group. The corresponding mortality hazard ratio was 0.76, which was associated with p-value less than 0.0001. Results from the PSM sensitivity analysis were similar, demonstrating a median overall survival as 57.8 months in the palbociclib group and 43.5 months in the AI-alone group, with a corresponding hazard ratio of 0.72, with a p-value less than 0.0001.
DR HOPE RUGO: For real-world progression-free survival, median durations were 19.3 months for palbociclib and 13.9 months for AI alone. The corresponding hazard ratio was 0.70, with a p-value less than 0.0001. PSM results for real-world progression-free survival were consistent with those using sIPTW, with median durations of 19.8 months for palbociclib and 14.9 months for AI alone. The corresponding hazard ratio was 0.72, with a p-value less than 0.0001. Subgroup analyses indicated that the overall and real-world progression-free survival benefits associated with palbociclib persisted for most patients, regardless of race, visceral disease, bone-only disease, or de novo metastatic diagnosis after either sIPTW or PSM.
DR HOPE RUGO: We also looked at subsequent treatments among patients. During the follow-up period, 49% of palbociclib and 65% of AI-alone recipients receive subsequent treatments. Of these, 43% of palbociclib and 51% of AI-alone recipients received a second-line CDK4/6 inhibitor. Approximately 20% of palbociclib recipients who received subsequent treatment received either chemotherapy or endocrine therapy alone as subsequent therapy. Whereas in the AI-alone group, 15% received chemotherapy and 30% received endocrine therapy alone.
Segment:5 Discussion.
DR HOPE RUGO: Real-world progression-free survival findings from this study are similar to those from two 2021 palbociclib comparative analyses that also used the Flatiron database. Brufsky and colleagues found that sIPTW real-world progression-free survival was 20.2 months among palbociclib plus letrozole recipients versus 16.9 months among letrozole-only recipients, with a hazard ratio of 0.71, a 95% confidence interval of 0.60 to 0.83. Progression-free survival estimates reported by DeMichele and co-workers were 20 months for palbociclib plus letrozole versus 11.9 months for letrozole only, a hazard ratio of 0.58, with 95% confidence intervals from 0.49 to 0.69. Importantly, the two-year overall survival rate reported by DeMichele was higher in the palbociclib group at 78%, compared with the letrozole-only group at 68%, although median overall survival was not reached in the palbociclib group in either analysis.
DR HOPE RUGO: Overall survival findings from this study differ from those in PALOMA-2, in which the numeric increase in overall survival associated with palbociclib was not statistically significant. Possible reasons for this difference include powering of PALOMA-2 based on the primary endpoint of progression-free survival rather than the secondary endpoint of overall survival. In contrast, overall survival was the primary endpoint in P-REALITY-X, which had a patient population nearly five times that of PALOMA-2 and therefore had greater likelihood of detecting improvements in overall survival.
DR HOPE RUGO: Patient characteristics also differed between the two studies, with median age in P-REALITY-X of 70 years versus 61 to 62 years in PALOMA-2. Additionally, most patients in PALOMA-2 were enrolled from academic medical centers, whereas more than 90% of patients in P-REALITY-X were treated in community medical centers. Finally, PALOMA-2 findings reflect a small number of patients who met rigorous eligibility criteria and were treated under closely monitored clinical trial conditions. Whereas P-REALITY-X findings are derived from patients treated in routine clinical practice and may therefore be comparatively more generalizable.
DR HOPE RUGO: In general, caution should be taken when evaluating consistency between clinical trial and real-world findings. Study strengths include the scope and diversity of the Flatiron database, large sample size, long median follow-up, contemporaneous control arm, validation of overall survival, and real-world progression-free survival in the Flatiron database, and pre-specified primary and secondary endpoints. Additionally, sIPTW and PSM were used to reduce the risk of confounding due to demographic and clinical characteristics.
DR HOPE RUGO: Potential limitations include retrospective database analysis, possible missing or erroneous electronic health record data, small sample sizes in some subgroups, possible confounding effects of unobserved variables, lack of standardized criteria for establishing disease progression, and potential lack of generalizability to other populations.
Segment:6 Conclusion.
DR HOPE RUGO: In summary, P-REALITY-X is the largest, multi-site, real-world comparative analysis to date to evaluate effectiveness of palbociclib combination therapy with AIs for HR positive/ HER2 negative MBC. Results demonstrated prolonged overall survival and real-world progression-free survival associated with receipt of palbociclib plus an AI compared with AI alone among these patients. These benefits were observed for most subgroups of patients analyzed, including those not well represented in breast cancer clinical trials such as black patients and patients 75 years of age or older. These results support the use of palbociclib plus an AI as first-line therapy for patients with HR positive/HER2 negative MBC.
Segment:7 Closing.
DR HOPE RUGO: [MUSIC PLAYING]
Segment:1 Introduction.
[MUSIC PLAYING]
DR HOPE RUGO: On behalf of myself and my authors, I am pleased to present our paper, "Overall Survival with Palbociclib Plus Aromatase Inhibitor Versus Aromatase Inhibitor Alone in Postmenopausal Women and Men with Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, a Large, Real-world Study in US Clinical Practice," published in NPJ Breast Cancer in 2022.
Segment:2 Background.
DR HOPE RUGO: Breast cancer accounts for nearly one third of all cancers among women. Breast cancer treatment recommendations are subtype specific. Approximately 2/3 of breast cancers are hormone receptor positive and human epidermal growth factor receptor two negative or HR positive/HER2 negative. The National Comprehensive Cancer Network, NCCN, guidelines recommend cyclin-dependent kinase 4/6 inhibitors or CDK4/6 inhibitors in combination with endocrine therapy as first line treatment for postmenopausal women, premenopausal women receiving ovarian ablation or suppression, or men with HR positive, HER2 negative Metastatic Breast Cancer, or MBC.
DR HOPE RUGO: The CDK4/6 inhibitor palbociclib was first approved in the United States in February 2015, in combination with the aromatase inhibitor or AI letrozole as first-line treatment for HR positive, HER2 negative metastatic breast cancer. Approval was expanded to include any AI in 2017. The pivotal phase 3 PALOMA-2 clinical trial demonstrated that patients receiving palbociclib plus letrozole had significantly longer progression-free survival than those receiving letrozole alone.
DR HOPE RUGO: Although clinical trials provide valuable drug effectiveness data, patients are subject to strict eligibility criteria and therefore may not represent most patients treated in routine clinical practice. Consequently, real-world studies are important for understanding effectiveness and in turn, informing treatment decisions for patients treated in clinical practice. Comparative real-world effectiveness studies for palbociclib have been limited. The P-REALITY-X study described here aimed to evaluate overall and real-world progression-free survival associated with palbociclib plus an AI versus an AI alone among patients with HR positive/ HER2 negative MBC.
Segment:3 Methods.
DR HOPE RUGO: P-REALITY-X was a retrospective cohort study that used data from the Flatiron Health Analysis Database, a longitudinal database containing de-identified, structured and unstructured electronic health record data from more than three million US cancer patients. Flatiron has an extensive and rigorous data abstraction and harmonization process to ensure optimal data quality for analyses used for regulatory purposes and in peer-reviewed publications.
DR HOPE RUGO: Included patients were treatment-naive, postmenopausal women and men, 18 years of age or older who were first prescribed palbociclib plus an AI or an AI alone for HR positive/HER2 negative MBC between February 3rd, 2015 and March 31st, 2020. Follow-up extended through September 30th, 2020, death, or the patient's last visit, whichever was first.
DR HOPE RUGO: The primary outcome was overall survival, defined as the number of months from the start of treatment with palbociclib plus an AI or an AI alone until death. The secondary outcome was real-world progression-free survival, defined as the number of months from the start of treatment to the first documentation of real-world progressive disease or death due to any cause, whichever occurred first. Disease progression was assessed by the treating clinician using radiology, laboratory evidence, pathology, or clinical assessment. Median survival times for both endpoints were estimated using the weighted Kaplan-Meier method, and hazard ratios were calculated using weighted Cox proportional hazard models.
DR HOPE RUGO: Endpoints were compared across treatment groups using three statistical methods. The unadjusted analysis simply compared the endpoints without controlling for baseline patient characteristics. The stabilized Inverse Probability Treatment Weighting method, sIPTW, and Propensity Score Matching, PSM, are commonly used statistical approaches for real-world data to control for potential confounding effects due to the lack of study randomization. sIPTW was the primary analysis used, and PSM was the sensitivity analysis.
Segment:4 Results.
DR HOPE RUGO: 2,888 patients were included in the study, of whom 1,324 received palbociclib plus an AI, and 1,564 received an AI alone. In the unadjusted cohort, more patients in the palbociclib group had Eastern Cooperative Oncology Group scores of zero, de novo metastatic breast cancer, lower comorbidity indices, and a higher number of metastatic sites, compared with the AI group alone.
DR HOPE RUGO: Patient demographic and clinical characteristics were generally balanced after both sIPTW and PSM, with most standardized differences for each characteristic being less than 0.1. After sIPTW, median patient age was 70 years in both groups and approximately 1/3 of patients were 75 or older. Approximately 2/3 of patients in each group were white and 9% were black. Approximately 30% of patients in each group had visceral disease. Most patients were treated in community practices, with 8% in each group treated at academic medical centers. Median follow-up duration after sIPTW was 23.9 months in the palbociclib group and 24.5 months in the AI-alone group.
DR HOPE RUGO: Median overall survival and real-world progression-free survival was longer in the palbociclib group, compared with the AI-alone group across the unadjusted sIPTW and PSM analyses. After sIPTW, median overall survival was 49.1 months in the palbociclib group, compared with 43.2 months in the AI group. The corresponding mortality hazard ratio was 0.76, which was associated with p-value less than 0.0001. Results from the PSM sensitivity analysis were similar, demonstrating a median overall survival as 57.8 months in the palbociclib group and 43.5 months in the AI-alone group, with a corresponding hazard ratio of 0.72, with a p-value less than 0.0001.
DR HOPE RUGO: For real-world progression-free survival, median durations were 19.3 months for palbociclib and 13.9 months for AI alone. The corresponding hazard ratio was 0.70, with a p-value less than 0.0001. PSM results for real-world progression-free survival were consistent with those using sIPTW, with median durations of 19.8 months for palbociclib and 14.9 months for AI alone. The corresponding hazard ratio was 0.72, with a p-value less than 0.0001. Subgroup analyses indicated that the overall and real-world progression-free survival benefits associated with palbociclib persisted for most patients, regardless of race, visceral disease, bone-only disease, or de novo metastatic diagnosis after either sIPTW or PSM.
DR HOPE RUGO: We also looked at subsequent treatments among patients. During the follow-up period, 49% of palbociclib and 65% of AI-alone recipients receive subsequent treatments. Of these, 43% of palbociclib and 51% of AI-alone recipients received a second-line CDK4/6 inhibitor. Approximately 20% of palbociclib recipients who received subsequent treatment received either chemotherapy or endocrine therapy alone as subsequent therapy. Whereas in the AI-alone group, 15% received chemotherapy and 30% received endocrine therapy alone.
Segment:5 Discussion.
DR HOPE RUGO: Real-world progression-free survival findings from this study are similar to those from two 2021 palbociclib comparative analyses that also used the Flatiron database. Brufsky and colleagues found that sIPTW real-world progression-free survival was 20.2 months among palbociclib plus letrozole recipients versus 16.9 months among letrozole-only recipients, with a hazard ratio of 0.71, a 95% confidence interval of 0.60 to 0.83. Progression-free survival estimates reported by DeMichele and co-workers were 20 months for palbociclib plus letrozole versus 11.9 months for letrozole only, a hazard ratio of 0.58, with 95% confidence intervals from 0.49 to 0.69. Importantly, the two-year overall survival rate reported by DeMichele was higher in the palbociclib group at 78%, compared with the letrozole-only group at 68%, although median overall survival was not reached in the palbociclib group in either analysis.
DR HOPE RUGO: Overall survival findings from this study differ from those in PALOMA-2, in which the numeric increase in overall survival associated with palbociclib was not statistically significant. Possible reasons for this difference include powering of PALOMA-2 based on the primary endpoint of progression-free survival rather than the secondary endpoint of overall survival. In contrast, overall survival was the primary endpoint in P-REALITY-X, which had a patient population nearly five times that of PALOMA-2 and therefore had greater likelihood of detecting improvements in overall survival.
DR HOPE RUGO: Patient characteristics also differed between the two studies, with median age in P-REALITY-X of 70 years versus 61 to 62 years in PALOMA-2. Additionally, most patients in PALOMA-2 were enrolled from academic medical centers, whereas more than 90% of patients in P-REALITY-X were treated in community medical centers. Finally, PALOMA-2 findings reflect a small number of patients who met rigorous eligibility criteria and were treated under closely monitored clinical trial conditions. Whereas P-REALITY-X findings are derived from patients treated in routine clinical practice and may therefore be comparatively more generalizable.
DR HOPE RUGO: In general, caution should be taken when evaluating consistency between clinical trial and real-world findings. Study strengths include the scope and diversity of the Flatiron database, large sample size, long median follow-up, contemporaneous control arm, validation of overall survival, and real-world progression-free survival in the Flatiron database, and pre-specified primary and secondary endpoints. Additionally, sIPTW and PSM were used to reduce the risk of confounding due to demographic and clinical characteristics.
DR HOPE RUGO: Potential limitations include retrospective database analysis, possible missing or erroneous electronic health record data, small sample sizes in some subgroups, possible confounding effects of unobserved variables, lack of standardized criteria for establishing disease progression, and potential lack of generalizability to other populations.
Segment:6 Conclusion.
DR HOPE RUGO: In summary, P-REALITY-X is the largest, multi-site, real-world comparative analysis to date to evaluate effectiveness of palbociclib combination therapy with AIs for HR positive/ HER2 negative MBC. Results demonstrated prolonged overall survival and real-world progression-free survival associated with receipt of palbociclib plus an AI compared with AI alone among these patients. These benefits were observed for most subgroups of patients analyzed, including those not well represented in breast cancer clinical trials such as black patients and patients 75 years of age or older. These results support the use of palbociclib plus an AI as first-line therapy for patients with HR positive/HER2 negative MBC.
Segment:7 Closing.
DR HOPE RUGO: [MUSIC PLAYING]
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