bims-cyhorp 2022-11-27 papers

Issue of 2022–11–27
four papers selected by
Piotr Okupski,

Ecancermedicalscience. 2022 ;16 1450

Efficacy of cyclin-dependent kinase 4/6 inhibitors in patients with metastatic hormone positive breast cancer: a single institutional study from India.

Sandip Ganguly, Navonil Mukherjee, Sayan Mandal, Somnath Roy, Sanjit Agarwal, Bivas Biswas, Joydeep Ghosh.

Purpose: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have shown marked benefit in the treatment of hormone positive metastatic breast cancer (HR+ MBC). There are limited real-world studies with palbociclib and ribociclib. Here we report our experience with CDK4/6 inhibitors in these groups of patients.
Material and methods: Patients with HR+ MBC who have received either palbociclib or ribociclib during the course of their treatment from January 2017 to January 2022 were included in the study. The baseline demographic features, treatment details and toxicity were recorded. Patients who received at least 1 month of therapy were included in the survival analysis.
Results: A total of 144 patients received CDK4/6 inhibitors during the time period. The median age of the population was 53 (30-80) years. Ninety-eight (71.4%) patients presented with de novo metastatic disease. The most common site of metastasis was to the skeleton (74.2%). Most patients (75%) received palbociclib as their therapy. At a median follow-up of 20.2 months, the median progression free survival (PFS) of the whole population was 16.5 (95% confidence interval (95% CI): 11.6-25.5) months and the median overall survival (OS) was 29.7 (95% CI: 21.7-44.6) months. The presence of liver metastases, low progesterone receptor positivity (Allred score < 6) and prior systemic treatment were poor prognostic factors for both PFS and OS in multivariate analysis. Drug was discontinued for only 2.1% of the patient population.
Conclusions: Use of CDK4/6 inhibitors has led to improvement in PFS and OS in patients with HR+ MBC and it is well tolerated. The presence of liver metastases and low progesterone receptor positivity (Allred score < 6) and prior treatment are poor prognostic factors.

Keywords: India; breast cancer; palbociclib; ribociclib

DOI: https://doi.org/10.3332/ecancer.2022.1450

Breast Cancer Res Treat. 2022 Nov 21.

Patient characteristics, treatment patterns, and outcomes of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer patients prescribed cyclin-dependent kinase 4 and 6 inhibitors: large-scale data analysis using a Japanese claims database.

Masaaki Kawai, Masahiro Takada, Takahiro Nakayama, Norikazu Masuda, Hirokazu Shiheido, Zhihong Cai, Yu-Jing Huang, Tsutomu Kawaguchi, Yoshinori Tanizawa.

PURPOSE: The aim was to understand real-world cyclin-dependent kinase (CDK) 4 and 6 inhibitor use in Japan.
METHODS: This retrospective observational study used a Japanese administrative claims database and included patients with presumptive hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) prescribed CDK4 and 6 inhibitor therapy between December 2017 and March 2021. Patient characteristics, treatment patterns, and selected clinical and safety outcomes were descriptively summarized. Time to discontinuation (TTD) and chemotherapy-free survival (CFS) were examined using Kaplan-Meier estimates.
RESULTS: The study cohort (N = 6442) was predominantly female (99.4%; median [range] age 64 [26-99] years) with records of metastases (79.6%) within 1 year prior to initiating CDK4 and 6 inhibitor therapy. In total, 4463 (69.3%) and 1979 (30.7%) were prescribed palbociclib and abemaciclib, respectively, as their first CDK4 and 6 inhibitor, most commonly in combination with fulvestrant (n = 3801; 59.0%). Overall, 3756 patients initiated a subsequent anticancer treatment, of whom 748 (19.9%) initiated a different CDK4 and 6 inhibitor in combination with the same or different endocrine therapy. Median TTD (95% confidence interval) was 9.7 (9.3, 10.1) months for the first CDK4 and 6 inhibitor therapy. Median CFS was 26.1 (24.6, 27.8) months. Incidence of clinically relevant diarrhea was higher after abemaciclib initiation (9.8%) than after palbociclib initiation (1.5%). More patients experienced dose reduction with palbociclib (69.3%) than with abemaciclib (53.0%).
CONCLUSION: The data provide insights into current clinical practices for CDK4 and 6 inhibitor use in Japan that could help establish future treatment strategies for ABC.

Keywords: Administrative claims database; CDK4 and 6 inhibitor; Effectiveness; Metastatic breast cancer; Real-world evidence; Safety

DOI: https://doi.org/10.1007/s10549-022-06816-9

Future Oncol. 2022 Nov 25.

PERFORM: a non-interventional study assessing the patients' treatment starting with 1L palbociclib in HR+/HER2- ABC.

Michael Patrick Lux, Eva Diana Runkel, Esther Glastetter, Corinne Vannier, Johanna Buncke, Melanie Frank, Rupert Bartsch, Marc Thill, Achim Wöckel.

The prospective, non-interventional PERFORM study describes and analyzes the effectiveness of palbociclib in combination with endocrine therapy (aromatase inhibitor or fulvestrant) as first-line treatment for patients with locally advanced or metastatic HR+/HER2- breast cancer in the real-world setting in Germany and Austria. PERFORM will reflect current patient characteristics and routine treatment patterns including treatment sequences and time to subsequent (chemo)therapy. Besides, second-line treatment effectiveness and patient-relevant end points such as longitudinal patient-reported outcome measurements beyond disease progression will be analyzed. Accounting for the heterogenous real-world patient population, data on clinicopathologic subgroups underrepresented in clinical trials such as elderly or male will be analyzed. Taken together, PERFORM will close knowledge gaps from clinical trials in real world.

Keywords: HR+/HER2- advanced breast cancer; PERFORM; PFS2; palbociclib; real-world evidence

DOI: https://doi.org/10.2217/fon-2022-0552

Clin Breast Cancer. 2022 Oct 13. pii: S1526-8209(22)00228-2. [Epub ahead of print]

Consequences of Discontinuing a 4/6 Cyclin D-Dependent Kinase Inhibitor During Endocrine Treatment in Hormone-Sensitive Metastatic Breast Cancer Patients in the Context of the COVID-19 Outbreak.

Sophie Martin, Carole Pflumio, Philippe Trensz, Frederique Schaff-Wendling, Michal Kalish- Weindling, Cathie Fischbach, Laure Pierard, Jean-Marc Limacher, Rita Nader, Michel Velten, Thierry Petit.

BACKGROUND: The impact of some hasty medical decision made during the first wave of the Coronavirus Disease 2019 (COVID-19) remains unknown. We have evaluated the consequences of one of these precautionary measures: the withdrawal of the cyclin D-dependent kinases 4/6 inhibitor (CDK4/6i) in patients whose metastatic disease was controlled by a combination of endocrine treatment and CDK 4/6i.
METHOD: This study was noninterventional, retrospective, multicentric, and included 60 patients with HR+ HER2- metastatic disease. Their disease was controlled with the combination of endocrine treatment and CDK 4/6i. The CDK 4/6i was stopped for two months during the first COVID-19 outbreak. A univariate analysis was performed to assess the risk factors associated with disease progression.
RESULTS: During this therapeutic break, 22 (37 %) patients had a radiological and/or clinical disease progression. Among them, the CDK 4/6i was re-introduced to 16 patients (n = 16/22; 73 %). A new line of treatment (chemotherapy or targeted therapy) was initiated due to the rapid symptomatic tumor progression in four patients (n = 4/22; 18 %). Two patients (n = 2/22) died in visceral crisis before another anti-tumoral treatment was introduced. In univariate analysis, the presence of liver metastases increased the risk of metastatic disease progression during the withdrawal of the CDK 4/6 (OR = 6.6; 95 % CI 1.87-23.22; P= .0033).
CONCLUSION: Progression was observed in 37% of patients during the two-month treatment interruption of the CDK 4/6i. A prolonged CDK 4/6i treatment interruption in patients with clinical benefit on endocrine treatment does not seem to be a reasonable option in light of these results.

Keywords: CDK4/6 inhibitors; COVID-19; Disease progression; Hepatic metastases; Treatment withdrawn

DOI: https://doi.org/10.1016/j.clbc.2022.10.006