First-in-human phase I study of BEBT-109 in previously treated EGFR exon 20 insertion-mutated advanced non-small cell lung cancer.

BACKGROUND: BEBT-109 is an oral pan-mutant-selective inhibitor of epidermal growth factor receptor (EGFR) that demonstrated promising antitumor potency in preclinical models. METHODS: This first-in-human study was a single-arm, open-label, two-stage study. Phase Ia dose-escalation study evaluated the safety and pharmacokinetics of BEBT-109 in 11 patients with EGFR T790M-mutated advanced non-small cell lung cancer (aNSCLC). Phase Ib dose-expansion study evaluated the safety and efficacy of BEBT-109 in 18 patients with EGFR exon 20 insertion (ex20ins)-mutated treatment-refractory aNSCLC. The primary outcomes were adverse events and antitumor activity. Clinical trial registration number CTR20192575. FINDINGS: The phase Ia study demonstrated no dose-limiting toxicity, no observation of the maximum tolerated dose, and no new safety signals with BEBT-109 in the dose range of 20-180 mg/d, suggesting that BEBT-109 had an acceptable safety profile among patients with EGFR T790M-mutated aNSCLC. Plasma pharmacokinetics of BEBT-109 showed a dose-proportional increase in the area under the curve and maximal concentration, with no significant drug accumulation. The dose-expansion study demonstrated that BEBT-109 treatment was tolerable across the three dose levels. The three most common treatment-related adverse events were diarrhea (100%; 22.2% ≥Grade 3), rash (66.7%; 5.6% ≥Grade 3), and anemia (61.1%; 0% ≥Grade 3). The objective response rate was 44.4% (8 of 18). Median progression-free survival was 8.0 months (95% confidence intervals, 1.33-14.67). CONCLUSION: Preliminary findings showed that BEBT-109 had an acceptable safety profile and favorable antitumor activity in patients with refractory EGFR ex20ins-mutated aNSCLC. FUNDING: National Natural Science Foundation of China.

Comparative retrospective review of perioperative analgesia using ultrasound-guided programmed intermittent erector spinae plane block for video-assisted thoracoscopic lobectomy.

BACKGROUND: The retrospective cohort study was conducted to estimate the opioid-sparing anesthesia and limited side-effects with ultrasound (US)-guided ESPB using programmed intermittent bolus (PIB) or continuous infusion (CI) and standard opioid-based anesthesia in patients undergoing video-assisted thoracoscopic lobectomy (VATS). METHODS: Patients underwent VATS were stratified into either control group or one of the two ESPB groups in a 1:2:2 ratio depending on whether PIB was implemented or not. The primary endpoint was intra- and post-operative opioids consumption over the first 48 h following surgery. RESULTS: A total of 180 cases were included in the analysis. Cumulative perioperative opioid administration was found to be significantly different between PIB, CI and control group (both p < 0.001), and between PIB and CI group (p = 0.028). More specifically, the mean was 305.30 ± 51.35 mg, 339.68 ± 56.07 mg and 468.91 ± 79.84 mg in PIB, CI and control group. NRS scores at rest across all postoperative times were comparable in two ESPB groups, while significantly lower than control group, however, scores during exercising at postoperative 3, 6, 12 h were significantly lower in PIB group as compared to CI group. A wider anesthetized dermatomes with PIB was observed at 6, 24 and 48 h as opposed to the CI. The mean of levobupivacaine plasma concentration was significantly lower for PIB at postoperative 0.5, 12, 24 and 48 h after initiation than CI. However, local anesthetic toxicity was not observed in any of the two ESPB groups. CONCLUSIONS: When US-guided ESPB using PIB was performed preoperatively, it contributed to the minimization of intra- and post-operative opioid consumption due to better analgesia with a wider anesthetic dermatome opposed to conventional CI, whereas, it was also associated with lower risk of local anesthetic toxicity because of lower plasma concentration of levobupivacaine.

Efficacy Evaluation of Zoledronic Acid Combined with Chemotherapy in the Treatment of Lung Cancer Spinal Metastases on Computed Tomography Images on Intelligent Algorithms.

To analyze the effectiveness and safety of zoledronic acid combined with chemotherapy for lung cancer spinal metastases, 96 patients with lung cancer spinal metastases were averagely classified into the experimental group (gemcitabine, cisplatin, and zoledronic acid) and the control group (gemcitabine and cisplatin). An optimized noise variance estimation algorithm (OMAPB) was proposed based on the maximum a posteriori Bayesian method (MAPB), and the algorithm was applied to the patient's computed tomography (CT) scan. The results indicated that in terms of curative effect, the number of complete remission (CR), partial remission (PR) cases, effective rate, and clinical benefit rate of the test group was significantly higher than those of the control group. The number of progress disease (PD) cases was significantly lower than that of the control group (P < 0.05). The disease progression time of the test group patients was 6.2 months, and the disease progression time of the control group patients was 3.7 months (P < 0.05). The test group patients had 8 cases of bone marrow suppression and gastrointestinal reactions after treatment. In the test group, there were 8 cases of bone marrow suppression, 9 cases of gastrointestinal reaction, 3 cases of fever, 4 cases of pain, and 2 cases of hair loss. The patients in the control group were complicated with bone marrow suppression in 14 cases, gastrointestinal reaction in 17 cases, fever in 5 cases, pain in 4 cases, and hair loss in 6 cases. The difference was statistically significant (P < 0.05). It showed that zoledronic acid combined with chemotherapy could effectively improve the treatment efficiency and clinical benefit rate of patients with lung cancer spinal metastases, prolong the progression of the disease, reduce the degree of bone tissue damage, and would not increase chemotherapy adverse events.

Effect of the Iron Reduction Index on the Mechanical and Chemical Properties of Continuous Basalt Fiber.

Basalt glass belongs to the iron-rich aluminosilicate glass system; thus, the iron content and the iron redox index (IRI=Fe2+/Fetotal) influence the viscosity, density, mechanical and chemical properties of basalt fiber (BF). In this work, continuous BFs with IRIs ranging from 0.21-0.87 were prepared by adding a different amount of redox agents. An economical and easily accessible testing method-the spectral photometric method with 1,10-phenanthroline-is applied to measure the IRI with convinced accuracy, which has been approved by Mössbauer spectra and X-ray fluorescence analysis. The tensile strength of the BF samples increases approximately linearly with increasing IRI as a function of σ = 227.9 IRI + 780.0 . The FT-IR results indicate that, with increasing IRI, the ferric ions are replaced by the much stronger network formers (Al3+ and Si4+), hence the increased the tensile strength. The X-ray diffraction results show an amorphous nature of BF samples. Moreover, the tensile strength is significantly decreased after the alkali corrosion, which is partly attributed to the severe surface damaging according to the SEM results. This work proved the feasibility of mechanical property improvement in BF production by controlling the iron redox index.

[The poor chemotherapeutic efficacy in lung adenocarcinoma overexpressing c-Src and nucleophosmin/B23(NPM1)].

Objective To observe the expressions of c-Src protein and nucleophosmin/B23 (NPM1) protein in lung adenocarcinoma tissues and explore their relationships with chemotherapeutic efficacy. Methods The study collected a total of 107 lung adenocarcinoma tissue specimens from the First People's Hospital of Huaihua City from 2012-10-10 to 2015-06-30. Immunohistochemistry was used to analyze the expressions of c-Src protein and NPM1 protein. The relationships between the protein expressions and lung adenocarcinoma progression were subsequently analyzed. Among these patients, 55 cases of III-IV patients were treated with gemcitabine combined with cisplatin for 4 cycles of chemotherapy. The relationships between the protein expressions and chemotherapeutic efficacy were then analyzed. Results Both c-Src protein and NPM1 protein were positively expressed in lung adenocarcinoma tissues. With the increase of clinical stages, their expression levels gradually increased. However, their levels showed an inverse correlation with tumor differentiation degree. Chemotherapeutic efficacy decreased with the increase of the protein expressions. Conclusion Chemotherapeutic sensitivity is poor in lung adenocarcinoma patients overexpressing c-Src and NPM1 protein. High expressions of c-Src and NPM1 may be associated with poorly differentiated adenocarcinoma.