Safety and Efficacy of Palbociclib and Radiation Therapy in Patients With Metastatic Breast Cancer: Initial Results of a Novel Combination

Chowdhary, Mudit; Sen, Neilayan; Chowdhary, Akansha; Usha, Lydia; Cobleigh, Melody A.; Wang, Dian; Patel, Kirtesh R.; Barry, Parul; Rao, Ruta

doi:10.1016/j.adro.2019.03.011

Cited by 52 publications

(40 citation statements)

References 11 publications

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“…Two lesions (5%) developed radiation necrosis, and both of them underwent four previous RT courses before the occurrence of radionecrosis, indicating the significance of cautious assessment of the treatment plan margins. Chowdhary et al [86] reported that concomitant treatment with palbociclib and RT resulted in grade 1 or 2 toxicity and notably relieved pain. Also, no local failure was noted in evaluable follow-up patients.…”

Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 99%

“…Currently, there are six ongoing clinical trials (Table 3 ) as well as several small sample clinical studies (Table 4 ), which mostly target HR+/HER2- metastatic breast cancer (MBC) patients. The preliminary results [ 83 – 86 ] propose that no significantly increased toxicity is observed, indicating that the combined therapy is promising as a novel strategy. Ippolito et al [ 84 ] reported that hematological toxicity neutropenia is most common among all adverse events.…”

Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 99%

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CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

Yang

Luo

Chen

et al. 2020

J Exp Clin Cancer Res

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Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination.

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Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 99%

Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 99%

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

Yang

Luo

Chen

et al. 2020

J Exp Clin Cancer Res

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“…Larger subsequent series provided a broader perspective regarding the safety of concomitant treatment with CDK4/6 inhibitors and radiotherapy. Chowdary et al evaluated the safety and efficacy of palbociclib in 16 breast cancer patients that received RT for symptomatic metastases 33 . No significant toxicity increase was observed compared to rates reported for palbociclib alone; prolonged pain control was achieved in all patients, and no local failures were described.…”

Section: Resultsmentioning

confidence: 99%

A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients

Guerini

Pedretti

Salah

et al. 2020

Sci Rep

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Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3-4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3-4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease. Selective cyclin dependent kinases 4/6 (CDK4/6) inhibitors block tumor suppressor retinoblastoma protein phosphorylation, preventing the transition of cancer cells from G1 to S phase with consequent inhibition of cell cycle and proliferation 1. To date, three CDK4/6 inhibitors are approved against hormone receptor positive, human epidermal growth factor receptor 2 negative metastatic or advanced breast cancer in combination with aromatase inhibitors or fulvestrant both in first and subsequent lines of therapy. After different phase III trials 2-7 reporting significant improvements in response rate and progression free survival, palbociclib was the

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“…In January 2019, a retrospective study reported outcome of 16 breast cancer patients with bone metastases radiotherapy and palbociclib. [39]. Six patients had concurrent fulvestrant and ten had letrozole.…”

Section: Palbociclibmentioning

confidence: 99%

CDK 4/6 inhibitors combined with radiotherapy: A review of literature

Bosacki

Bouleftour

Sotton

et al. 2021

Clinical and Translational Radiation Oncology

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Safety and Efficacy of Palbociclib and Radiation Therapy in Patients With Metastatic Breast Cancer: Initial Results of a Novel Combination

Cited by 52 publications

References 11 publications

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients

CDK 4/6 inhibitors combined with radiotherapy: A review of literature

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