CDK 4/6 inhibitor induced lung injury: a case report and review of literature

Abstract

Palbociclib is a cyclin dependent kinase (CDK) 4/6 inhibitor that is indicated in combination with an aromatase inhibitor for first-line treatment of hormone receptor-positive, human epidermal growth factor receptor 2 -negative advanced or metastatic breast cancer. The commonly described side effects of palbociclib are neutropenia, anaemia, thrombocytopenia, fatigue, nausea, stomatitis, alopecia, diarrhoea, decreased appetite, vomiting, asthenia, peripheral neuropathy and epistaxis. However, post approval, increasing use of this drug has revealed another potentially fatal complication, in the form of pneumonitis, especially in the Asian population. The PALOMA 3 trial showed that rates of grade 3 and grade 4 adverse events were modestly higher in Asians than non-Asians, though palbociclib exposure was similar in both races. From this, we could infer that adverse effects of this drug must be monitored more specifically in individual racial populations. We report a patient who developed pneumonitis while on palbociclib and discuss the possible mechanisms and management of CDK 4/6 inhibitor-related lung injury.

Post-Marketing Safety Concerns With Palbociclib A Disproportionality Analysis of the FDA Adverse Event

“…Still, it did not improve lung function and led to the accumulation of in ammatory factors (including macrophages and T cells) in the lung 39 . The same phenomenon has been observed in clinical cases 40,41 . In the event of pneumonia that is suspected to be due to palbociclib, palbociclib should be discontinued, and glucocorticoids and oxygen therapy should be used as appropriate 41 .…”

Interstitial lung disease in patients treated with Cyclin-Dependent Kinase 4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials

“…related to these agents have been reported, indicating a potential association between CDK4/6 inhibitors and ILD/pneumonitis [48][49][50][51][52][53].…”

“…An in vivo study suggested that palbociclib augmented inflammatory cell recruitment (including macrophages and T cells) in the bronchoalveolar lavage fluid, which could be a consequence of the palbociclib-induced cell cycle arrest with relevant cellular senescence [44,61]. It was further proposed that in the presence of cell cycle inhibitor like palbociclib, the inflammatory cell milieu was altered, which could leading to cell senescence [51,62]. This speculation might explain the reason why CDK4/6 inhibitors caused lung injury.…”

Breathless on the journey: Unmasking palbociclib-induced pneumonitis in a geriatric breast cancer warrior

“…Although palbociclib is generally well tolerated, pulmonary toxicity associated with palbociclib is a rare but potentially serious adverse event. 1 , 2 …”