Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer

Rugo, Hope S.; Liu, Xianchen; Li, Benjamin; McRoy, Lynn; Layman, Rachel M.; Brufsky, Adam

doi:10.1016/j.breast.2023.03.015

Cited by 11 publications

(16 citation statements)

References 22 publications

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“…Most of the RWE studies were retrospective ( n = 32) [ 30 – 59 ]; three studies were prospective [ 60 – 65 ], and two were ambispective (retrospective and prospective) studies [ 66 , 67 ]. Three retrospective studies using data from the Flatiron Health longitudinal database had different study time frames and populations (in terms of patient age); however, there remains a possibility of patient overlap across studies [ 35 , 37 , 52 ]. Older patients were defined as ≥ 60 years of age in one study [ 40 ], ≥ 65 years in 21 studies [ 30 , 32 , 34 , 36 – 39 , 42 , 43 , 45 , 46 , 49 , 50 , 52 , 53 , 56 – 58 , 64 , 65 , 68 ], ≥ 70 years in 11 studies [ 31 , 44 , 47 , 48 , 54 , 55 , 59 – 63 , 66 , 67 ], and ≥ 75 years in four studies [ 33 , 35 , 41 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Of the included 37 RWE studies, seven included only older patients [ 37 , 41 , 43 , 59 – 63 ]. Among RWE studies including both younger and older patients, six studies provided data on the proportion of patients aged ≥ 75 years (31% [1960 of 6380]) [ 36 , 37 , 45 , 46 , 51 , 52 ]. Data from a total of 12 studies for patient demographics and baseline characteristics in older patients who received palbociclib were limited and heterogeneous (most studies only described the total patient population).…”

Section: Resultsmentioning

confidence: 99%

“…In one study, rwPFS rate at 12 months was significantly longer in patients ≥ 65 years of age versus patients aged < 65 years [ 64 ]. Six studies included only older patients [ 33 , 35 , 37 , 41 , 59 , 60 ]; in one study using multivariable regression, age (as a continuous variable) was not a significant predictor of rwPFS [ 41 ]. In all three RWE studies with a control arm (two of these three studies included only older patients [ 35 , 37 ]), older patients treated with palbociclib had significantly longer rwPFS compared with control treatment [ 35 , 37 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

“…Six studies included only older patients [ 33 , 35 , 37 , 41 , 59 , 60 ]; in one study using multivariable regression, age (as a continuous variable) was not a significant predictor of rwPFS [ 41 ]. In all three RWE studies with a control arm (two of these three studies included only older patients [ 35 , 37 ]), older patients treated with palbociclib had significantly longer rwPFS compared with control treatment [ 35 , 37 , 52 ]. Of note, all three studies were controlled for potential biases by using stabilized inverse probability of treatment weighting or propensity score matching or both [ 35 , 37 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

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Palbociclib in Older Patients with Advanced/Metastatic Breast Cancer: A Systematic Review

Brain,

Chen,

Simon

et al. 2024

Targ Oncol

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Background Palbociclib in combination with endocrine therapy is approved for treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer. In addition to clinical trials, several real-world studies have evaluated the effectiveness of palbociclib. With increased life expectancy in the general population, breast cancer in older women is also expected to increase. Objective The aim was to systematically review evidence from both clinical trials and real-world studies for palbociclib treatment outcomes in older patients with HR+/HER2− advanced/metastatic breast cancer (a/mBC). Older patients are often underrepresented in clinical trials, and real-world evidence (RWE) will enrich the analysis of palbociclib outcomes in this subgroup of patients. Design A systematic literature search in PubMed, EMBASE, and Cochrane Library through May 4, 2023, yielded 2355 unique articles. A total of 52 articles (13 and 39 articles reporting results from seven randomized controlled trials [RCTs] and 37 RWE studies, respectively) were included based on study eligibility criteria. Results All RCTs used age cutoffs of ≥ 65 years to define older population ( n = 722; 437 received palbociclib); all RWE studies, except one with an age cutoff of > 60 years, had age cutoffs of ≥ 65 years or higher to define older population ( n = 9840; 7408 received palbociclib). Overall, in studies that compared efficacy (progression-free survival [seven RCTs, 20 RWE studies], overall survival [four RCTs, 11 RWE studies], tumor response [three RWE studies], and clinical benefit rate [one RCT, two RWE studies]) and safety outcomes (three RCTs, three RWE studies) between older and younger patients, palbociclib showed similar benefits, regardless of age. Results from two RCTs and two RWE studies showed that global quality of life (QoL) was maintained in older patients receiving palbociclib. Overall, palbociclib dose modifications (two RWE studies), dose reductions (one RCT, seven RWE studies), and treatment discontinuation rates (three RCTs, three RWE studies) were higher in older patients compared with younger patients; however, these differences did not appear to adversely impact efficacy outcomes. Conclusions In this systematic review, data from RCTs showed that palbociclib was effective, well tolerated, and maintained QoL in older patients with HR+/HER2− a/mBC. Palbociclib treatment in older patients in real-world settings was associated with similar clinical benefit as in RCTs. PROSPERO Registration CRD42023444195. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-024-01046-z.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Palbociclib in Older Patients with Advanced/Metastatic Breast Cancer: A Systematic Review

Brain,

Chen,

Simon

et al. 2024

Targ Oncol

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Tolerability and effectiveness of palbociclib in older women with metastatic breast cancer

Baltussen,

Mooijaart,

Vulink

et al. 2024

Breast Cancer Res Treat

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Purpose Palbociclib has become the standard of care for estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer, but real-world evidence in older women remains scarce. Therefore, we investigated tolerability of palbociclib in older women with metastatic breast cancer. Methods Consecutive women aged ≥ 70 with ER+/HER2- metastatic breast cancer, treated with palbociclib in any treatment line in six hospitals, were included. Primary endpoint was grade ≥ 3 palbociclib-related toxicity. Predictors of toxicity were identified using logistic regression models. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier. Results We included 144 women with a median age of 74 years. Grade 3–4 toxicity occurred in 54% of patients, of which neutropenia (37%) was most common. No neutropenic fever or grade 5 toxicity occurred. Dose reduction during treatment occurred in 50% of patients, 8% discontinued treatment due to toxicity and 3% were hospitalized due to toxicity. Polypharmacy (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.12–5.58) and pretreatment low leukocytes (OR 4.81; 95% CI 1.27–18.21) were associated with grade 3–4 toxicity, while comorbidities were not. In first-line systemic therapy, median PFS was 12 months and median OS 32 months. In second-line, median PFS was 12 months and median OS 31 months. Conclusion Although grade 3–4 toxicity and dose reductions occurred frequently, most were expected and managed by dose reductions, showing that palbociclib is generally well tolerated and thus represents a valuable treatment option in the older population.

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First- vs second-line CDK 4/6 inhibitor use for patients with hormone receptor positive, human epidermal growth-factor receptor-2 negative, metastatic breast cancer in the real world setting

Kimmick,

Pilehvari,

You

et al. 2024

Breast Cancer Res Treat

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Purpose To compare CDK4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) in the first- versus second-line setting for treatment of hormone receptor positive (HR+), HER2 negative, metastatic breast cancer (MBC) using real-world evidence. Methods Patients with HR+, HER2 negative MBC, diagnosed between 2/3/2015 and 11/2/2021 and having ≥ 3 months follow-up were identified from the nationwide electronic health record-derived Flatiron Health de-identified database. Treatment cohorts included: (1) first-line ET with a CDK 4/6i (1st-line CDK4/6i) versus (2) first-line ET alone followed by second-line ET with a CDK4/6i (2nd-line CDK4/6i). Differences in baseline characteristics were tested using chi-square tests and two-sample t-tests. Time to third-line therapy, time to start of chemotherapy, and overall survival were compared using Kaplan-Maier method. Results The analysis included 2771 patients (2170 1st-line CDK4/6i and 601 2nd-line CDK4/6i). Patients receiving 1st-line CDK4/6i were younger (75% vs 68% < 75 years old, p = 0.0001), less likely uninsured or not having insurance status documented (10% vs. 13%, p = 0.04), of better performance status (50% vs 43% with ECOG 0, p = 0.03), and more likely to have de novo MBC (36% vs. 24%, p < 0.001). Time to third-line therapy (49 vs 22 months, p < 0.001) and time to chemotherapy (68 vs 41 months, p < 0.001) were longer in those receiving first-line CDK4/6i. Overall survival (54 vs 49 months, p = 0.33) was similar between groups. Conclusion Use of CDK4/6i with first-, vs second-, line ET was associated with longer time to receipt of 3rd-line therapy and longer time to receipt of chemotherapy.

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Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer

Cited by 11 publications

References 22 publications

Palbociclib in Older Patients with Advanced/Metastatic Breast Cancer: A Systematic Review

Palbociclib in Older Patients with Advanced/Metastatic Breast Cancer: A Systematic Review

Tolerability and effectiveness of palbociclib in older women with metastatic breast cancer

First- vs second-line CDK 4/6 inhibitor use for patients with hormone receptor positive, human epidermal growth-factor receptor-2 negative, metastatic breast cancer in the real world setting

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