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Simple Summary: Palbociclib is one of the preferred treatments for hormone-receptor-positive, HER2-negative metastatic breast cancer in women; its effectiveness and safety in the Chinese real-world population require further investigation. Our study aimed to identify the clinical outcomes of patients who received palbociclib in combination with endocrine therapy (ET) in China. The effectiveness of palbociclib plus ET in treating metastatic breast cancer was confirmed in 397 Chinese patients across eight clinical sites. The regimens were well tolerated by both the general and elderly groups. However, some factors were identified as potential hindrances to the therapy's benefits, including higher Ki-67 expression, primary resistance to ETs, liver metastases, more metastatic sites, later line of therapy, and the use of fulvestrant instead of aromatase inhibitors. Palbociclib is useful for treatment of metastasis breast cancer, and our study may provide a basis for further research. Background: Palbociclib has been approved for marketing in China. However, its effectiveness, safety, and latent variables in the Chinese population require further investigation. Methods: Information was retrieved from 397 patients with metastatic breast cancer (mBC) who received at least two cycles of palbociclib plus endocrine therapy (PAL plus ET) at eight clinical sites in China. The patients' demographic characteristics, treatment patterns, and adverse events (AEs) were analyzed. Results: The objective response rate (ORR) and clinical benefit rate (CBR) for PAL plus ET were 28.97% and 66.25%, respectively. The median PFS was 14.2 months in the whole population. In addition to protein Ki-67 status and sensitivity to ETs, no liver metastases, fewer metastatic sites, an earlier line of therapy, and treatment combined with AI instead of FUL were also considered as independent prognostic factors for PAL treatment. Administration of PAL was generally well tolerated in patients with hormone-receptor-positive and human-epidermal-growth-factor-receptor-2-negative (HR+/HER2−) advanced breast cancer (ABC). The therapy was safe in the elderly population, which is consistent with the outcomes of the whole population and previous reports. Conclusions: In this most widely distributed study in China to date, palbociclib combined with ET proved its effectiveness for HR+/HER2− ABC treatment, and adverse events were manageable. Here, we identified some independent prognosis factors, but the mechanism by which these factors influence effectiveness requires further verification. [ABSTRACT FROM AUTHOR]

Simple Summary: Although multiple actionable genes have been identified in melanoma, 38–42% of patients are still not druggable based on current research. In our study, DNA-NGS and RNA-NGS were utilized to construct molecular profiles of a Chinese cohort of 469 melanoma patients. Up to 11.7% (7/60) of patients in the undruggable group could be recognized as actionable by DNA and RNA sequential sequencing. Additionally, the use of RNA-NGS enhanced the proportion of druggable fusions from 2.56% to 17.27%. In total, the use of RNA-NGS increased the druggable proportion from 75% to 78%. Our study systemically analyzed the genetic landscape of Asian melanoma and demonstrated how DNA and RNA sequential sequencing is essential in bringing clinical benefits to more melanoma patients. Background: In contrast to Caucasian melanoma, which has been extensively studied, there are few studies on melanoma in Asian populations. Sporadic studies reported that only 40% of Asian melanoma patients could be druggable, which was much lower than that in Caucasians. More studies are required to refine this conclusion. Methods: Chinese melanoma patients (n = 469) were sequentially sequenced by DNA-NGS and RNA-NGS. The genomic alterations were determined, and potentially actionable targets were investigated. Results: Patients with potential druggable targets were identified in 75% of Chinese melanoma patients by DNA-NGS based on OncoKB, which was much higher than in a previous Asian study. NRG1 fusions were first identified in melanoma. In addition, up to 11.7% (7/60) of patients in the undruggable group could be recognized as actionable by including RNA-NGS analysis. By comparing the fusion detection rate between DNA-NGS and RNA-NGS, all available samples after DNA-NGS detection were further verified by RNA-NGS. The use of RNA-NGS enhanced the proportion of druggable fusions from 2.56% to 17.27%. In total, the use of RNA-NGS increased the druggable proportion from 75% to 78%. Conclusions: In this study, we systemically analyzed the actionable landscape of melanoma in the largest Asian cohort. In addition, we first demonstrated how DNA and RNA sequential sequencing is essential in bringing clinical benefits to more patients with melanoma. [ABSTRACT FROM AUTHOR]