Trillium Health Partners, Mississauga, ON L5M 2N1, Canada.
Institute for Better Health, Trillium Health Partners, Mississauga, ON L5M 2N1, Canada.
Curr Oncol. 2022 Mar 7;29(3):1761-1772. doi: 10.3390/curroncol29030145.
Palbociclib, a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor, in combination with letrozole or fulvestrant has been demonstrated to prolong the progression-free survival (PFS) in patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer. In efforts to mitigate neutropenic toxicities, oncologists in real-world practice have prescribed alternative dosing strategies with palbociclib, yet the implication on PFS is unknown.
We conducted a retrospective, observational chart review of all female patients at our clinics with HR+, HER2- metastatic breast cancer receiving palbociclib in combination with either letrozole or fulvestrant with a first dose initiated between June 2016 and December 2018 and followed their disease course until 30 April 2020.
The median PFS for all clinic patients receiving palbociclib and letrozole ( = 63) was 40.8 months (95% confidence interval (CI) 25.6-not estimable) and 16.97 months (95% CI 8.57-not estimable) for patients receiving palbociclib and fulvestrant ( = 11). We identified seven alternative dosing strategies prescribed by oncologists, the most prevalent being prescribing palbociclib for three weeks on and two weeks off ( = 8). The Kaplan-Meier curves for PFS in patients receiving letrozole and palbociclib prescribed alternative dosing strategies appear to diverge from monograph dosing early in the treatment. Many patients prescribed palbociclib using alternative dosing strategies continued to be observed even by the 18-month timepoint. The prevalence of grade 4 neutropenia was lower for patients on palbociclib with letrozole, suggesting a possible mitigation of severe neutropenia with alternative dosing strategies.
We conclude that alternative dosing strategies used by oncologists such as prescribing palbociclib for three weeks on, two weeks off may achieve comparable disease control while mitigating neutropenic toxicities when compared to standard monograph dosing recommendations, prolonging treatment tolerability and adherence. Further large-scale studies are needed to confirm these results for future clinical adoption.
帕博西尼是一种细胞周期蛋白依赖性激酶 4 和 6（CDK4/6）抑制剂，与来曲唑或氟维司群联合应用已被证明可延长激素受体阳性（HR+）、人表皮生长因子 2 阴性（HER2-）转移性乳腺癌患者的无进展生存期（PFS）。为了减轻中性粒细胞减少症的毒性，临床医生在实际治疗中采用了帕博西尼的替代剂量策略，但对 PFS 的影响尚不清楚。
我们对我院 2016 年 6 月至 2018 年 12 月期间接受帕博西尼联合来曲唑或氟维司群治疗的 HR+、HER2-转移性乳腺癌女性患者进行了回顾性观察性图表审查，并对所有患者进行了随访，直至 2020 年 4 月 30 日。
所有接受帕博西尼联合来曲唑治疗的患者的中位 PFS 为 63 个月（95%置信区间（CI）25.6-不可估计），接受帕博西尼联合氟维司群治疗的患者的中位 PFS 为 16.97 个月（95%CI 8.57-不可估计）。我们发现临床医生开了七种替代剂量策略，最常见的是帕博西尼每三周服用一次，两周停药一次（ = 8）。接受来曲唑和帕博西尼治疗的患者的 PFS 生存曲线，根据处方的替代剂量策略，在治疗早期似乎与说明书剂量的曲线分道扬镳。许多接受帕博西尼替代剂量策略治疗的患者甚至在 18 个月时仍继续被观察。接受帕博西尼联合来曲唑治疗的患者中性粒细胞减少症 4 级的发生率较低，这表明替代剂量策略可能减轻了严重中性粒细胞减少症的毒性。
我们的结论是，临床医生采用的替代剂量策略，如帕博西尼每三周服用一次，两周停药一次，可能与标准说明书剂量推荐相比，达到相当的疾病控制效果，同时减轻中性粒细胞减少症的毒性，延长治疗的耐受性和依从性。需要进一步的大规模研究来证实这些结果，以便将来在临床上采用。
