The Food and Drug Administration approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals LP) in combination with platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (la/mNSCLC) who have tumors with EGFR exon 19 deletions or exon 21 L858R mutations, as identified by an FDA-approved test, on February 16, 2024.
The test was done in FLAURA 2 (NCT04035486), a random, open-label study with 557 people who had either EGFR exon 19 deletion or exon 21 L858R mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) and had not had any systemic treatment for advanced illness before. Patients were randomly assigned in a 1:1 ratio to receive either osimertinib plus platinum-based chemotherapy or osimertinib alone.
The primary efficacy measure was progression-free survival (PFS), evaluated by the investigator, with overall survival (OS) as a significant secondary measure. When osimertinib was combined with platinum-based chemotherapy, progression-free survival (PFS) was much higher than when osimertinib was used alone. The hazard ratio was 0.62 (95% CI: 0.49–0.79; two-sided p-value<0.0001). The median progression-free survival (PFS) was 25.5 months with a 95% confidence interval (CI) of 24.7 to not estimable (NE) in one arm, and 16.7 months with a 95% CI of 14.1 to 21.3 in the other arm.
Although the overall survival statistics were not fully developed at the current analysis, with just 45% of the pre-specified fatalities reported for the final analysis, there was no indication of a negative trend.
Leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail damage, dry skin, and high blood creatinine levels were some of the most common side effects that happened to people who were given osimertinib along with platinum-based chemotherapy.
The suggested osimertinib dosage is 80 mg taken orally once a day, with or without food, until disease progression or unacceptable toxicity. Consult the prescribing information for pemetrexed with cisplatin or carboplatin for the specific dose details.
Targeting FGFR4 and CD276 with CAR T-cells demonstrates a strong antitumor impact against children rhabdomyosarcoma
Chimeric antigen receptor (CAR) T-cells that specifically target Fibroblast Growth Factor Receptor 4 (FGFR4), a surface tyrosine receptor that is extensively expressed in rhabdomyosarcoma (RMS), are now undergoing clinical research. However, the effectiveness of these CAR T-cells may be hindered by tumor heterogeneity and inadequate activation. In this study, we present a method to enhance the co-stimulatory and targeting characteristics of a FGFR4 CAR through an optimization process. We substituted the hinge and transmembrane domain of CD8 as well as the 4-1BB co-stimulatory domain with the corresponding domains of CD28. The CARs produced exhibit heightened anti-tumor efficacy in multiple RMS xenograft models, with the exception of the RMS559 cell line, which is known for its aggressive nature.
