Statement of Key Findings
The study results indicated comprehensive disparities in the AE profiles between PAL and ABE. Many AEs, including cytopenia and nervous system and psychiatric disorders, were frequent with PAL, while interstitial lung disease, diarrhoea, and renal and urinary disorders were frequent with ABE.
Strengths and Weaknesses
This study had several limitations. First, although the VigiBase and FAERS databases are widely used in pharmacovigilance studies, the data are based on spontaneous reports, which can cause reporting bias, erroneous data, or missing data. Second, controlling confounding factors was more difficult in pharmacovigilance studies than in clinical trials, making it difficult to achieve the same level of rigor. Lastly, the data obtained from the databases did not include cases where AEs did not occur; thus, the incidence of AEs could not be calculated. Hence, the results obtained in this study are qualitative rather than quantitative. Despite these limitations, this study can be sufficiently useful because it allows for a comprehensive analysis of multiple AEs using real-world data and for estimating the AE profile of PAL and ABE.
Interpretation
Although meta-analyses of clinical trials and retrospective studies conducted in the United States have compared the AE profiles of CDK4/6 inhibitors [11, 12], the current study analysed a large sample of global pharmacovigilance ABE or PAL data. To the best of our knowledge, this is the first study to comprehensively evaluate differences in AE frequency between PAL and ABE using a large-scale database, rather than relying on data from clinical trials or single-country study. The two databases used in this study, VigiBase and FAERS, were similar at the SOC level and mostly consistent at the PT level. Overall, this indicates increased reliability and certainty in our results.
According to a report summarizing previous clinical trials, neutropenia is more frequent in PAL, while diarrhoea, nausea, and liver dysfunction are more frequent in ABE [13]. The most common reasons for dose modification were myelosuppression for PAL and diarrhoea for ABE [14]. Therefore, these AEs affect tolerability. Severe interstitial pneumonia related to both PAL and ABE has been reported; however, its frequency has not been clear [13]. Our findings also revealed that cytopenia, alopecia, fatigue, and stomatitis were frequent in patients using PAL, whereas diarrhoea, vomiting, and liver dysfunction were frequent in patients using ABE. Additionally, the frequency of interstitial lung disease was higher for ABE. Overall, these results are consistent with those of previous reports and reflect clinical practice sufficiently.
Patients receiving ABE exhibited increased blood creatinine levels, renal failure, and acute kidney injury. Therefore, users of ABE may need to be treated with caution to prevent worsening of renal function. Although ABE-induced nephrotoxicity is considered rare, a case of grade 4 acute kidney injury has previously been reported [15]. ABE has been shown to inhibit creatinine transporters in renal tubules, resulting in decreased creatinine clearance and increased serum creatinine levels [16]. Other markers, such as blood urea nitrogen or cystatin C, may also be used to accurately assess renal function in patients undergoing ABE therapy.
Further research
Interestingly, in our study, patients receiving PAL frequently experienced psychiatric disorders. In particular, depression is associated with poor medication compliance and can affect cancer treatment outcomes [17]. Furthermore, other AEs likely to affect the quality of life of patients included peripheral neuropathy, dyspnoea, arthralgia, myalgia, and visual impairment with PAL and tachycardia with ABE. There are some limitations in the database analysis; therefore, further retrospective and prospective studies are needed to determine the disparity in AEs between both drugs.