A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Tuning the Packing Density of Gold Nanoparticles in Peptoid Nanosheets Prepared at the Oil-Water Interface.

Two-dimensional (2D) arrays of gold nanoparticles that can freely float in water are promising materials for solution-based plasmonic applications like sensing. To be effective sensors, it is critical to control the interparticle gap distance and thus the plasmonic properties of the 2D arrays. Here, we demonstrate excellent control over the interparticle gap distance in a family of freely floating gold nanoparticle-embedded peptoid nanosheets. Nanosheets are made via monolayer assembly and collapse at the oil-water interface, allowing for fine control over the solution nanoparticle concentration during assembly. We used surface pressure measurements to monitor the assembly of the peptoid, nanoparticle, and combined system at the oil-water interface to determine a workable range of nanosheet assembly conditions suitable for controlling the interparticle gap distances within the nanosheets. These measurements revealed that the extent of nanoparticle adsorption to the peptoid monolayer can be tuned by varying the bulk nanoparticle concentration, but the ability for the monolayer to collapse into nanosheets is compromised at high nanoparticle concentrations. Peptoid nanosheets were synthesized with varying bulk nanoparticle concentrations and analyzed using light microscopy and UV-visible spectroscopy. Based on the spectral shift of the localized surface plasmon resonance peaks for the nanoparticles in the nanosheets relative to those well dispersed in toluene, we estimate that we can access interparticle gap distances within the nanosheet interior between 2.9 ± 0.5 and 9 ± 2 nm. Our results suggest that the minimum interparticle distance achievable by this method is limited by the nanoparticle ligand length, and so has the potential to be further tuned by varying the ligand chemical structure. The ability to quantitatively control and monitor the assembly conditions by this method provide an opportunity to readily tune the optoelectronic properties of this new class of 2D nanomaterial, making it a promising platform for plasmonic-based sensing applications.

Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo.

Mutations in the BK polyomavirus (BKPyV) capsid accumulate in kidney transplant (KTx) recipients with persistent virus replication. They are associated with neutralization escape and appear to arise as a result of cytosine deamination by host cell APOBEC3A/B enzymes. To study the mutagenic processes occurring in patients, we amplified the typing region of the VP1 gene, sequenced the amplicons to a depth of 5000-10,000×, and identified rare mutations, which were fitted to COSMIC mutational signatures. Background mutations were identified in amplicons from plasmids carrying the BKPyV genome and compared to mutations observed in 148 samples from 23 KTx recipients in France and in Vietnam. Three mutational signatures were consistently observed in urine, serum, and kidney biopsy samples, two of which, SBS2 and SBS13, corresponded to APOBEC3A/B activity. In addition, a third signature with no known etiology, SBS89, was detected both in patient samples, and in cells infected in vitro with BKPyV. Quantitatively, APOBEC3A/B mutation rates in urine samples were strongly correlated with urine viral load, and also appeared to vary between individuals. These results confirm that APOBEC3A/B is a major, but not the only, source of BKPyV genome mutations in patients.