Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non–Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor Receptor Mutation in Either Exon 19 or 21

Background:Gefitinib and erlotinib, small-molecule kinase inhibitors that block epidermal growth factor receptor (EGFR) signaling, have demonstrated a dramatic response rate and prolonged progression-free survival (PFS) in patients harboring an activating EGFR mutation. We compared the clinical outcomes in gefitinib- and erlotinib-treated patients harboring EGFR mutations who had recurrent or metastatic non–small-cell lung cancer (NSCLC).Methods:A total of 375 patients with recurrent or metastatic stage IIIB/IV NSCLC, who had either exon 19 deletion or the L858R mutation in exon 21, and had received either gefitinib (n = 228) or erlotinib (n = 147), were included in the study. A matched-pair case-control study design was implemented in the analysis, where 121 pairs of gefitinib-treated and erlotinib-treated patients were matched according to sex, smoking history, Eastern Cooperative Oncology Group performance status, and types of EGFR mutation.Results:The median age of all patients was 58 years (range, 30–84), and more than half of patients had never been smokers (63.6%). Most patients had adenocarcinoma (98.3%) and good Eastern Cooperative Oncology Group performance status (0, 1) (90.9%). The median number of cycles of EGFR tyrosine kinase inhibitor (TKI) treatment was 12.7 in the gefitinib group and 10.8 in the erlotinib group. Of the 242 patients, 63 (26%) received EGFR TKI as first-line therapy. The overall response rates and disease control rates in the gefitinib- or erlotinib-treated groups were 76.9% versus 74.4% (p = 0.575) and 90.1% versus 86.8%, respectively (p = 0.305). There was no statistically significant difference with regard to PFS (median, 11.7 versus 9.6; p = 0.056) between the gefitinib- and erlotinib-treated groups. For patients receiving EGFR TKI as the first-line treatment, there was no significant difference between the two treatment groups in overall response rates (76.7% and 90.0%) (p = 0.431) and median PFS (11.7 versus 14.5 months) (p = 0.507).Conclusion:In NSCLC patients harboring EGFR mutation, treatment with gefitinib and erlotinib resulted in similar effectiveness

Encorafenib plus binimetinib in patients with BRAFV600-mutant non-small cell lung cancer: phase II PHAROS study design

BRAF V600 mutation; Binimetinib; EncorafenibMutació de BRAF V600; Binimetinib; EncorafenibMutación de BRAF V600; Binimetinib; EncorafenibBRAFV600 oncogenic driver mutations occur in 1–2% of non-small-cell lung cancers (NSCLCs) and have been shown to be a clinically relevant target. Preclinical/clinical evidence support the efficacy and safety of BRAF and MEK inhibitor combinations in patients with NSCLC with these mutations. We describe the design of PHAROS, an ongoing, open-label, single-arm, phase II trial evaluating the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with metastatic BRAFV600-mutant NSCLC, as first- or second-line treatment. The primary end point is objective response rate, based on independent radiologic review (per RECIST v1.1); secondary objectives evaluated additional efficacy end points and safety. Results from PHAROS will describe the antitumor activity/safety of encorafenib plus binimetinib in patients with metastatic BRAFV600-mutant NSCLC

Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2)

Circulating tumor DNA; Non–small cell lung cancer; Tumor biomarkerADN tumoral circulante; Cáncer de pulmón de células no pequeñas; Biomarcador tumoralADN tumoral circulant; Càncer de pulmó de cèl·lules no petites; Biomarcador tumoralIntroduction Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor approved for treatment-naive and crizotinib-refractory advanced ALK-positive (ALK+) NSCLC. We evaluated brigatinib after other next-generation ALK tyrosine kinase inhibitors. Methods In this single-arm, phase 2, ALK in Lung Cancer Trial of brigAtinib-2 (NCT03535740), patients with advanced ALK+ NSCLC whose disease progressed on alectinib or ceritinib received brigatinib 180 mg once daily (after 7-d 90-mg lead-in). Primary end point was independent review committee (IRC)-assessed overall response rate (ORR). Circulating tumor DNA (ctDNA) was analyzed. Results Among 103 patients (data cutoff: September 30, 2020; median follow-up [range]: 10.8 [0.5–17.7] mo), confirmed IRC-ORR was 26.2% (95% confidence interval [CI]: 18.0–35.8), median duration of response, 6.3 months (95% CI: 5.6–not reached), and median progression-free survival (mPFS), 3.8 months (95% CI: 3.5–5.8). mPFS was 1.9 months (95% CI: 1.8–3.7) in patients with ctDNA-detectable baseline ALK fusion (n = 64). Among 86 patients who progressed on alectinib, IRC-ORR was 29.1% (95% CI: 19.8–39.9); mPFS was 3.8 months (95% CI: 1.9–5.4). Resistance mutations were present in 33.3% (26 of 78) of baseline ctDNA; 54% (14 of 26) of mutations were G1202R; 52% (33 of 64) of patients with detectable ALK fusion had EML4-ALK variant 3. Most common all-grade treatment-related adverse events were increased creatine phosphokinase (32%) and diarrhea (27%). The mean dose intensity of brigatinib (180 mg once daily) was 85.9%. Conclusions In ALK in Lung Cancer Trial of brigAtinib-2, brigatinib was found to have a limited activity in patients with ALK+ NSCLC post-ceritinib or post-alectinib therapy. mPFS was longer with brigatinib in patients without baseline detectable plasma ALK fusion

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial

Bintrafusp alfa; NSCLC; PD-L1Bintrafusp alfa; NSCLC; PD-L1Bintrafusp alfa; NSCLC; PD-L1Introduction Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1–high advanced NSCLC. Methods This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1–high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. Results Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1–16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1–15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo–not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo–NR]; hazard ratio = 1.232 [95% CI: 0.885–1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo–NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo–NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796–1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. Conclusions First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1–high, advanced NSCLC.The trial was sponsored by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder identification: 10.13039/100009945) and was previously part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline. The healthcare business of Merck KGaA, Darmstadt, Germany provided the trial drugs. The investigators worked with the healthcare business of Merck KGaA, Darmstadt, Germany on the trial design, collection and analysis of data, and interpretation of results. The authors thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers and the healthcare business of Merck KGaA, Darmstadt, Germany. The medical writing support was provided by Joyce Lee, PhD, ClinicalThinking, which was funded by the healthcare business of Merck KGaA, Darmstadt, Germany, and was previously part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3)

Gender differences in the distal radial artery diameter for the snuffbox approach

Background: Recently, interventional cardiologists have been increasingly interested in snuffbox approach for coronary angiography (CAG) and percutaneous coronary intervention (PCI). However, there is lack of data regarding distal radial artery (RA) diameter according to gender. Therefore, the aim herein was to investigate gender differences in the diameter of distal RA diameter. Methods: Left snuffbox approach was done in 117 patients who had planned CAG or PCI for suspected myocardial ischemia between 1 December 2017 and 28 February 2018 at the Chonnam National University Hospital, Gwangju, Korea. Left RA angiography was achieved from 101 patients. Among 101 individuals, 69 (68.3%) men and 32 (31.7%) women were enrolled. There was no significant difference in systolic and diastolic blood pressure, body mass index, left ventricular systolic function, or patients with acute coronary syndrome in either group. Results: The average diameter of distal RA was 2.57 mm in all patients. Women had a significantly smaller diameter of distal RA than men (2.40 mm vs. 2.65 mm, p = 0.016). Nevertheless, CAG via snuffbox approach by 6 Fr sheath was successfully performed in all 117 patients. Regarding success rate of the distal RA approach, women had a lower success rate (32/38) compared with men (72/79), but not significantly (84.2% vs. 91.1%, p = 0.264). Conclusions: Females has a significantly smaller distal RA diameter compared to males. Moreover, the success rate of the distal RA approach tends to be higher in men than in women