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

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

The Breast: Published: March 27, 2023

Background

Palbociclib, the first available cyclin-dependent kinase 4/6 inhibitor, plus endocrine therapy is approved for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). This study compared real-world effectiveness of palbociclib plus letrozole versus letrozole in older patients with MBC in US clinical practice.

Methods

This retrospective analysis included patients from the Flatiron Health longitudinal database. Overall, 796 women with HR+/HER2- MBC aged ≥65 years starting palbociclib plus letrozole or letrozole as first-line therapy between February 2015 and September 2018 were included. Patients were evaluated from treatment start until December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS), overall survival (OS), and real-world best tumor responses (rwBTR) were endpoints. Stabilized inverse probability treatment weighting (sIPTW) balanced patient characteristics.

Results

After sIPTW, 450 patients treated with palbociclib plus letrozole and 335 treated with letrozole were included; median age was 74.0 years. Median rwPFS was 22.2 (95% CI, 20.0–30.4) months for palbociclib plus letrozole versus 15.8 (12.9–18.9) months for letrozole (hazard ratio, 0.59 [0.47–0.74]; P < 0.001). Median OS was not reached for palbociclib plus letrozole versus 43.4 months (30.0-not estimable) with letrozole (hazard ratio, 0.55 [0.42–0.72]; P < 0.001). No interactions between age groups (65–74 and ≥ 75 years) and treatment groups were observed for rwPFS or OS. Rate of rwBTR was significantly higher for palbociclib plus letrozole (52.4%) versus letrozole (22.1%; odds ratio, 2.0 [1.4–2.7]; P < 0.001).

Conclusion

This analysis demonstrates the effectiveness of palbociclib combination therapy as standard-of-care for older patients with HR+/HER2- MBC in the first-line setting.

 

Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study

 

by Salma El Badri, Bilal Tahir, Kirsty Balachandran, Pavel Bezecny, Fiona Britton, Mark Davies, Karen Desouza, Simon Dixon, Daniel Hills, Maung Moe, Thomas Pigott, Andrew Proctor, Yatri Shah, Richard Simcock, Anna Stansfeld, Alicja Synowiec, Marianna Theodoulou, Mark Verrill, Anshu Wadhawan, Catherine Harper-Wynne, Caroline Wilson

 

The Breast: FULL LENGTH ARTICLE| VOLUME 60, P199-205, DECEMBER 01, 2021

 

Background

Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years.

Methods

14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities.

Results

276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia.

Conclusion

Palbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.

The role of CDK4/6 inhibitors in early breast cancer

 

The role of CDK4/6 inhibitors in early breast cancer

 

by Miguel Gil-Gil, Emilio Alba, Joaquín Gavilá, Juan de la Haba-Rodríguez, Eva Ciruelos, Pablo Tolosa, Daniele Candini, Antonio Llombart-Cussac 

 

The Breast: VOLUME 58, P160-169, AUGUST  01, 2021

 

The use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has proven to be a successful strategy in the treatment of advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer (BC), leading to a strong interest in their possible role in the treatment of early luminal BC. In this review we collect the most relevant and recent information on the use of CDK4/6i for the treatment of early BC in the neoadjuvant and adjuvant settings. Specifically, we evaluate the results of the large phase 3 adjuvant trials recently released, which have yielded apparently divergent results.

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

 

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

by B. Porte, M. Carton, F. Lerebours, E. Brain, D. Loirat, L. Haroun, A. Bellesoeur, S. Bach Hamba, Y. Kirova, P. Cottu

The Breast: Open Access, November 13, 2020

Highlights

• Efficacy and safety of palbociclib in the treatment of advanced breast cancer in real-life are very close to those from the pivotal trials.

• In the endocrine naive and endocrine sensitive population, we have highlighted three poor prognostic factors ECOG performance status 2, previous endocrine therapy for advanced breast cancer and three metastatic sites or more.

ABSTRACT

Background Palbociclib is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with endocrine therapy. Emerging real-life data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report the Institut Curie hospital experience.Patients and methods We retrospectively reviewed all patients with HR+ HER2- ABC treated with a palbociclib-based therapy as first or second line for ABC, with an initial prescription from November 2016 to December 2018. Clinical, laboratory and imaging data were retrieved from electronic records. Data lock was December 31st, 2019. Descriptive analyses, univariate and multivariate Cox regression analyses were performed. Results We included 310 consecutive patients. Median age was 61.8 years old. Palbociclib was prescribed in first line in 225 patients (72.6%). Before palbociclib-based therapy initiation, 122 patients (39.3%) were endocrine naive, 96 (31.0%) endocrine sensitive and 92 (29.7%) endocrine resistant. Median follow-up was 20.7 months. Median progression free survival (PFS) was 23.4 months (95%CI: 21.6-NR) in endocrine naive patients, 22.7 months (95%CI: 14.7-NR) in endocrine sensitive, and 13.4 months (95%CI: 10.7-20.8) in endocrine resistant. At 12 months from the initiation of palbociclib, 94.5% of patients were alive. By multivariate analysis, poor prognosis factors for PFS were identified in the endocrine naive/sensitive population: initial ECOG status 2, previous endocrine therapy for ABC, 3 metastatic sites or more. Toxicity profile was similar to previously published data.Conclusion In a non-selected population of patients with HR+ HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported.

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: results from the Compassionate Use Program in Spain (PALBOCOMP)

 

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: results from the Compassionate Use Program in Spain (PALBOCOMP)

 

The Breast:  VOLUME 54, P286-292, DECEMBER 01, 2020

 

Highlights

• CDK4/6 inhibitors combined with endocrine therapy have been widely accepted as a new standard therapy for hormone receptor-positive metastatic breast cancer patients in first or second line.

• Palbociclib alone or in combination with aromatase inhibitors, fulvestrant, or tamoxifen was effective and safe in heavily pretreated HR+/HER2- metastatic breast cancer patients.

• Palbociclib could be of higher benefit to patients with endocrine-sensitive disease that had a long duration of response to previous endocrine therapy.

• Real-world evidence of effectiveness and safety of use of palbociclib in heavily pretreated advanced breast cancer patients complements data from randomized clinical trials.

Abstract

Background

This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017.

Patients and methods

Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible.

Results

A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7–7.0) and the median overall survival was 19.0 months (95% CI 16.4–21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37–2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia.

Conclusions

Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.

[Articles] Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial

[Articles] Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial

by Yeon Hee Park, Tae-Yong Kim, Gun Min Kim, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Kyoung Eun Lee, Hee Kyung Ahn, Moon Hee Lee, Hee-Jun Kim, Han Jo Kim, Jong In Lee, Su-Jin Koh, Ji-Yeon Kim, Kyung-Hun Lee, Joohyuk Sohn, Sung-Bae Kim, Jin-Seok Ahn, Young-Hyuck Im, Kyung Hae Jung, Seock-Ah Im, Korean Cancer Study Group (KCSG)

The Lancet Oncology: ARTICLES| VOLUME 20, ISSUE 12, P1750-1759, DECEMBER 01, 2019

Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen.