The tumor biology revealed invasive ductal carcinoma grade 3: HR-positive, HER2-negative, and Ki67 of 30% (luminal B subtype). In January 2017, a 46-year-old premenopausal female presented to us with locally advanced breast cancer. In this article, we present a case of ribociclib-induced pneumonitis in a 46-year-old female with metastatic breast cancer. Recently, the Japanese ministry of health has released a warning as 4 patients developed pulmonary toxicity likely secondary to abemaciclib exposure, one of whom died. Three case reports on palbociclib-induced pneumonitis have been published, two of which improved after discontinuation of the drug, and one case report on abemaciclib-associated lung injury. There has been such evidence in the literature on the other CDK 4/6 inhibitors: palbociclib and abemaciclib. Since the publication of the trial, there has been no case of ribociclib-induced pulmonary toxicity reported. In the MONALEESA-2 trial, there were 2 deaths secondary to acute respiratory failure in patients receiving ribociclib plus letrozole. The most common grade 3 or 4 adverse reactions (reported in >2%) were neutropenia, leukopenia, abnormal liver function tests, and vomiting. The most common adverse reactions were neutropenia, thrombocytopenia, mucositis nausea, vomiting, fatigue, diarrhea, alopecia, constipation, headache, back pain, and QTc interval prolongation. Ribociclib is also in development for several indications in phase II trials such as liposarcoma, endometrial carcinoma, and high-grade neuroendocrine tumors. In the phase III MONARCH 2 trial, adding the CDK4/6 inhibitor abemaciclib to fulvestrant led to a median OS of 46.7 months compared with 37.3 months for placebo/fulvestrant in patients with HR-positive, HER2-negative advanced breast cancer who progressed on prior endocrine therapy (hazard ratio, 0.757 95% CI, 0.606–0.945 p = 0.0137). In updated findings, median OS was not reached for the patients on ribociclib versus 40.7 months for those on placebo (hazard ratio, 0.699 95% CI, 0.501–0.976). Similarly, the MONALEESA-7 trial looked at the addition of ribociclib to endocrine therapy in peri-/premenopausal women with advanced HR-positive, HER2-negative breast cancer. The median OS was not reached with ribociclib and was 40.0 months with placebo (hazard ratio, 0.724 95% CI, 0.568–0.924 p = 0.00455). The phase III MONALEESA-3 trial showed that the combination of ribociclib and fulvestrant led to an approximate 28% reduction in the risk of death compared with placebo and fulvestrant in postmenopausal patients with HR-positive, HER2-negative advanced breast cancer. Recently, these drugs have been shown in phase III trials to prolong overall survival (OS) in this population. Cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors have been proven to improve progression-free survival in women with advanced-stage hormone receptor (HR)-positive, HER2-negative breast cancer, resulting in approvals of three different agents (palbociclib, ribociclib, abemaciclib) and, in combination with endocrine therapies, in both first-line and second-line indications.
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