Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Abstract

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.

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

“…The average annual cost per patient for hospital admission due to toxicity was £342. 16. Given the small sample size and degree of imputation in calculating cost, this is an estimated average.…”

“…The average annual cost per patient for palbociclib toxicity-related hospitalisation in our study was £342. 16. One other UK study has looked at the costs of managing chemotherapy-associated toxicities in third line metastatic breast cancer patients and showed average annual costs ranging between £2621 and £2740 [19].…”

A eficácia dos novos tratamentos de hormonioterapia na sobrevida livre de progressão de pacientes com câncer de mama metastático RH+/HER2-: uma revisão sistemática

“…• Palbociclibe + letrozol: apresenta alta eficácia como tratamento de primeira linha para mulheres na pós-menopausa com câncer de mama metastático RH+/HER2-, que não receberam terapia sistêmica prévia para o câncer de mama, conforme demonstrado pelos estudos PALOMA-1 e PALOMA-2, e pelo estudo observacional retrospectivo IRIS. Além de melhor índice de sobrevida livre de progressão, com média de 26,5 meses (95% IC 24,8-27,4), evidenciou-se maiores taxas de resposta objetiva ao tratamento (63,1% dos pacientes), quando comparado com letrozol em monoterapia (Brufsky et al, 2021;Finn et al, 2015;Kovač et al, 2020;Mycock et al, 2021;Rugo et al, 2016;Waller et al, 2019;Wilkie et al, 2019).…”

“…• Palbociclibe + fulvestranto: foi a primeira combinação com um inibidor de CDK 4 e 6 aprovada para o tratamento de mulheres com câncer de mama que progrediram para doença metastática após terapia hormonal prévia, sendo Research, Society andDevelopment, v. 10, n. 14, e85101421940, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i14.21940 geralmente empregada como terapia de segunda linha. No contexto de tratamento de primeira linha, sua eficácia é reduzida, com sobrevida livre de progressão em torno de 18,7 meses (García-Trevijano Cabetas et al, 2021;Mycock et al, 2021;Seki et al, 2019;Waller et al, 2019).…”

Cytotoxic Marine Alkaloid 3,10-Dibromofascaplysin Induces Apoptosis and Synergizes with Cytarabine Resulting in Leukemia Cell Death

“…Remarkably, CDK4 and CDK6 kinases are frequently overexpressed in leukemia and responsible for G1 to S phase cell cycle transition via retinoblastoma protein (RB) dependent activation of an E2F1 transcription factor. An inhibitor of CDK4/6, palbociclib (PD-0332991), was previously approved by FDA for treatmet of breast cancer and is currently undergoing several clinical trials in other malignancies [ 22 , 23 , 24 ]. Interestingly, palbociclib has been found to be a promising candidate to enhance AraC-induced AML cell death.…”