Adjuvant TKIs: still an optimal choice.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu SY
PROVIDER: S-EPMC6344745 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Adjuvant TKIs: still an optimal choice.
Journal of thoracic disease 20181201 12
Similar Datasets
Project description:Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide. In about 55% of cases, it is diagnosed at a localised and/or locally advanced stage and therefore amenable to a curative approach. Although nephrectomy still represents the cornerstone of non-metastatic RCC (nmRCC) treatment, a relapse is observed in about 25-30% of patients undergoing curative surgery. Prognosis is drastically influenced by lymph nodal involvement. After the first disappointing results with a cytokine-based strategy, tyrosine kinase inhibitors (TKIs) were tested as adjuvant agents. Despite their efficacy in the metastatic setting, results in terms of disease-free survival (DFS) are not unequivocal and the overall survival (OS) benefit has not been demonstrated. Moreover, their toxicity profile induced a remarkable percentage of patients to discontinue the treatment. On the contrary, the KEYNOTE-564 trial showed the benefit of adjuvant pembrolizumab compared with placebo in terms of DFS with promising results in term of OS. Patients included were at intermediate or high risk of relapse, or patients with no evidence of disease after metastasectomy (M1 NED). The updated analysis presented at the American Society of Clinical Oncology Genito-Urinary (ASCO GU) 2022 confirmed the benefit of pembrolizumab versus placebo over time, although OS data are still immature. A longer follow-up and the several ongoing trials with immune checkpoint inhibitors (ICIs) will provide further data about adjuvant immuno-oncology (IO). Furthermore, the patients' selection based on clinical or biological features will be crucial in order to identify who benefits most from treatments.
| S-EPMC9584769 | biostudies-literature
Project description: Not available
| S-EPMC7481596 | biostudies-literature
Project description:BackgroundRecent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma.MethodsTwo hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated.ResultsThere were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445).ConclusionsAdjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.
| S-EPMC8167779 | biostudies-literature
Project description:Despite radiotherapy (RT) is recognized as preferred initial therapy for early-stage low-grade follicular lymphoma (FL) by many international practice guidelines, the medical oncologist has improperly underutilized RT, and diverse management strategies, including systemic therapy (ST), combined modality (CM) and watch and wait (WW), are still used. Except survival outcomes, previous studies concerned little about the treatment-related toxicity, which is also important factor in choosing initial management strategy, especially second primary malignancies (SPMs). The aim of this study was to compare the overall survival (OS) and the SPMs risk between different management strategies, which can provide guidance for the choice of optimal initial management strategy. Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Finally, A total 10,900 patients were identified, in which 930 cases developed SPMs. The use of radiotherapy (RT) has remained consistently low, with a utilization rate of around 20%, while most patients have received watchful waiting (WW) and systemic therapy (ST). In the rituximab era, multivariate analysis indicated that RT exhibited significantly superior OS and did not increase SPMs risk in comparison with ST and WW. At the same time, although there were no significant differences in OS between CM and RT, RT had significantly lower SPMs risk in comparison with CM. The use of RT improved the OS and did not increase the SPMs risk in comparison with other management strategies. Considering the low application rate of RT, oncologists should emphasize and increase the use of RT as an initial management strategy in patients with early-stage low-grade FL.
| S-EPMC11534986 | biostudies-literature
Project description:Different synonymous codons are favored by natural selection for translation efficiency and accuracy in different organisms. The rules governing the identities of favored codons in different organisms remain obscure. In fact, it is not known whether such rules exist or whether favored codons are chosen randomly in evolution in a process akin to a series of frozen accidents. Here, we study this question by identifying for the first time the favored codons in 675 bacteria, 52 archea, and 10 fungi. We use a number of tests to show that the identified codons are indeed likely to be favored and find that across all studied organisms the identity of favored codons tracks the GC content of the genomes. Once the effect of the genomic GC content on selectively favored codon choice is taken into account, additional universal amino acid specific rules governing the identity of favored codons become apparent. Our results provide for the first time a clear set of rules governing the evolution of selectively favored codon usage. Based on these results, we describe a putative scenario for how evolutionary shifts in the identity of selectively favored codons can occur without even temporary weakening of natural selection for codon bias.
| S-EPMC2700274 | biostudies-literature
Project description: Not available
| S-EPMC7575955 | biostudies-literature
Project description:BACKGROUND:Malignant mixed Mullerian tumors of endometrial (MMMT-E) and ovarian (MMMT-O) origin are associated with poor prognosis. Suggestively epithelial-driven tumors, their treatment has shifted from anthracycline or ifosfamide-based towards taxane-based chemotherapy. It remains unclear whether this change associates with better outcomes. PATIENTS AND METHODS:A conjoined Australian and Swiss patient cohort of MMMT-E (N = 103) and MMMT-O (N = 17) was compared to patients with adenocarcinoma of the endometrium (EC, N = 172) and ovary (OC, N = 189). Clinicopathological characteristics, FIGO stage, first-line treatment, and patient outcomes were analyzed. The generated hypothesis was verified in an US-American cohort with high-grade serous ovarian cancer (HGSOC, N = 1290) and MMMT-O (N = 450) using immunohistochemistry and next-generation sequencing. RESULTS:Early stage I/II MMMT-E showed a survival plateau after 2.5 years, with no recurrence or death observed afterwards. Relapse-free survival was significantly worse in MMMT-E treated with platinum/taxanes (P = 0.024) compared to non-taxane regimen. Hypothesizing that also MMMT-O might benefit from an adjuvant non-paclitaxel regimen, a second independent cohort of MMMT-O and HGSOC patients was examined. p53 mutations dominated in both cancers with comparable frequency. PI3KCA and KRAS mutations were less frequent: they were more frequent in MMMT-O than in HGSOC (P = 0.015 and P = 0.018, respectively). MMMT-O responded better to a combination of carboplatin with anthracyclines than with taxanes (73.9% vs. 39.4%). CONCLUSION:Early stage I/II MMMT-E patients have excellent prognosis if no recurrence has appeared within the first 2.5 years. In MMMT-E, platinum/anthracycline or ifosfamide regimen associated with better outcomes than platinum/taxanes regimens. This might also apply to MMMT-O.
| S-EPMC7039840 | biostudies-literature
Project description: Not available
| S-EPMC8105855 | biostudies-literature
Project description:Identification of epidermal growth factor receptor (EGFR) as a molecular target has radically changed the treatment of metastatic non-small cell lung cancer (NSCLC) from standard chemotherapy to personalized, targeted therapy. First-, second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) are now available for the treatment of EGFR-mutant NSCLC patients. This review will focus on the clinical development of first- and second-generation EGFR TKIs. We will emphasize on essential points like the head-to-head comparison among EGFR TKIs, their activity on brain metastases, mechanisms of resistance, as well as their combination with anti-angiogenic compounds, other targeted therapies, or immunotherapy. The efficacy of first- and second-generation EGFR TKIs in early-stage EGFR-mutant NSCLC will be also finally reviewed.
| S-EPMC8797317 | biostudies-literature
Project description:Advances in the management of gastric cancer have improved patient survival in the last decade. Nonetheless, the number of patients relapsing and dying after a diagnosis of localized gastric cancer is still too high, even in early stages (10% in stage I). Adjuvant systemic chemotherapy has been proven to significantly improve outcomes. In the present article we have critically reviewed the clinical trials that guide the current clinical practice in the adjuvant treatment of patients affected by resectable gastric cancer, focusing on the different approaches worldwide, i.e., adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy. We also delineate the clinical-pathological characteristics that are commonly taken into account to identify patients at a higher risk of recurrence and requiring adjuvant chemotherapy, and also describe novel biomarkers and therapeutic agents that might allow personalization of the treatment.
| S-EPMC9563297 | biostudies-literature