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International Journal of Cancer Jul 2019Osimertinib is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI). A meta-analysis... (Meta-Analysis)
Meta-Analysis
Osimertinib is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI). A meta-analysis was performed to aggregate the mixed results of published clinical trials to assess the efficacy and safety of osimertinib. A systematic search of the PubMed, Web of Science, and Cochrane Library electronic databases was performed to identify eligible literature. The primary endpoints were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events (AEs). A total of 3,086 advanced nonsmall cell lung cancer (NSCLC) patients from 11 studies have been identified. The aggregate efficacy parameters for treatment-naïve patients with EGFR-TKI-sensitizing mutations are as follows: ORR 79% (95% CI 75-84%), DCR 97% (95% CI 95-99%), 6-month PFS 83% (95% CI 80-87%), and 12-month PFS 64% (95% CI 59-69%). The aggregate efficacy parameters for advanced NSCLC harboring T790M mutations after earlier-generation EGFR-TKI therapy are as follows: ORR 58% (95% CI 46-71%), DCR 80% (95% CI 63-98%), 6-month PFS 63% (95% CI 58-69%), and 12-month PFS 32% (95% CI 17-47%). EGFR-TKI-naïve patients with EGFR-positive mutations tend to have longer median PFS than EGFR-TKI-pretreated counterparts (19.17 vs. 10.58 months). The most common AEs were diarrhea and rash, of which the pooled incidences were 44 and 42%, respectively. Generally, osimertinib is a favorable treatment option for previously treated T790M mutation-positive advanced NSCLC as well as a preferable therapy for untreated EGFR mutation-positive advanced NSCLC. Additionally, osimertinib is well tolerated by most patients.
Topics: Acrylamides; Aniline Compounds; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 30613959
DOI: 10.1002/ijc.32097 -
BMC Cancer Jul 2020Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in...
BACKGROUND
Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in colorectal cancer (CRC), data to support specific associations between KRAS mutations in CRC and diet are sparse. Here, we conducted a systematic review to summarize the current epidemiological evidence on the association between various dietary factors and KRAS mutations.
METHODS
PubMed, Science Direct, and Cochrane databases were searched for relevant studies published until December 31, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find associations between nutritional factors and CRC tumors with KRAS mutations in humans.
RESULTS
We identified 28 relevant studies to include in this systematic review. In-depth analyses showed unclear associations between nutritional factors and KRAS mutations in CRC. Most epidemiological studies in the same nutrient or food often reported conflicting and/or inconclusive findings, whereas for some dietary factors, the results were homogeneous.
CONCLUSIONS
Further research using a more robust prospective cohort study is needed to lend more credence to the epidemiological associations found between KRAS mutations and dietary factors.
Topics: Acrylamide; Beverages; Colorectal Neoplasms; Dairy Products; Diet; Dietary Fats; Dietary Fiber; Dietary Proteins; Food; Fruit; Genes, ras; Humans; Mutation; Nutrients; Vegetables
PubMed: 32723394
DOI: 10.1186/s12885-020-07189-2 -
Annals of Palliative Medicine Sep 2020Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR)TKI. Osimertinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Osimertinib is used to treat a certain type of non-small cell lung cancer. We review some of the main challenges in targeting EGFR, including lack of central nervous system penetration with most tyrosine kinase inhibitors, activity of osimertinib penetrating blood-brain barrier and the efficacy of osimertinib.
METHODS
Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, we conducted a systematic literature search in the databases PubMed, EMBASE, ISI Web of Science database on January 30, 2020, searching for studies investigating the osimertinib efficacy on patients with CNS metastases in EGFR-mutant non-small cell lung cancer (NSCLC). And Newcastle-Ottawa Scale (NOS) was used to assess the certainty in the evidence.
RESULTS
The pooled results showed that the overall response rate (ORR) and disease control rate (DCR) were 70% and 92%, respectively, in patients with T790M mutations. The efficacy of osimertinib was confirmed by the median progression free survival (PFS). In untreated advanced EGFR-mutated NSCLC with CNS metastases patients, the pooled ORR and DCR of osimertinib were 71% and 93%, respectively. And the combined median PFS, achieved by osimertinib, was 12.21 months. Above data proved that osimertinib has well activity in disease control, especially in first line.
CONCLUSIONS
This meta-analysis confirmed that in treatment-naive advanced NSCLC CNS metastases harboring EGFR-TKI-sensitizing mutations, Osimertinib showed impressive antitumor activity.
Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Central Nervous System; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 32954743
DOI: 10.21037/apm-20-605 -
BMC Cancer Jan 2019Osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy...
Impact on prognosis of rebiopsy in advanced non-small cell lung cancer patients after epidermal growth factor receptor-tyrosine kinase inhibitor treatment: a systematic review.
BACKGROUND
Osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy reveals T790M mutation after the first-line EGFR-TKI treatment. However, the prognosis of patients after rebiopsy, the most important outcome for cancer patients, has not been described sufficiently. This systematic review aimed to clarify whether rebiopsy contributes to improved prognosis in the first- or second-generation EGFR-TKI refractory patients.
METHODS
Using free word and control terms related to "non-small cell lung cancer" and "rebiopsy," we searched studies from Medical Literature Analysis and Retrieval System Online via PubMed, Embase, Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform. We included cohort studies and case reports written in English and judged whether each study answers our research questions.
RESULTS
Of the 144 studies included, only one reported the prognosis of patients with/without rebiopsy showing that in EGFR-TKI refractory non-small cell lung cancer patients, the post-progression survival (PPS) was significantly longer in patients who received rebiopsy and treatment based on a resistant mechanism (median PPS 24.2 months) than those who received rebiopsy and salvage regimen (median PPS 15.2 months, p = 0.002) and who did not receive rebiopsy (median PPS 9.7 months, p < 0.001). Most of the other studies reported the detection rate of T790M mutation or rebiopsy procedure.
CONCLUSIONS
Only a few previous studies have investigated the effectiveness of rebiopsy. Hence, further study is needed to determine the prognosis or adverse events of rebiopsy.
Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Biopsy; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Resistance, Neoplasm; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Piperazines; Prognosis; Protein Kinase Inhibitors; Survival Analysis
PubMed: 30683066
DOI: 10.1186/s12885-019-5309-x