Encapsulating CoNi nanoparticles into nitrogen-doped carbon nanotube arrays as bifunctional oxygen electrocatalyst for rechargeable zinc-air batteries.

The high theoretical specific energy and environmental friendliness of zinc-air batteries (ZABs) have garnered significant attention. However, the practical application of ZABs requires overcoming the sluggish kinetics associated with oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Herein, 3D self-supported nitrogen-doped carbon nanotubes (N-CNTs) arrays encapsulated by CoNi nanoparticles on carbon fiber cloth (CoNi@N-CNTs/CFC) are synthesized as bifunctional catalysts for OER and ORR. The 3D interconnected N-CNTs arrays not only improve the electrical conductivity, the permeation and gas escape capabilities of the electrode, but also enhance the corrosion resistance of CoNi metals. DFT calculations reveal that the co-existence of Co and Ni synergistically reduces the energy barrier for OOH conversion to OH, thereby optimizing the Gibbs free energy of the catalysts. Additionally, analysis of the change in energy barrier during the rate-determining step suggests that the primary catalytic active center is Ni site for OER. As a result, CoNi@N-CNTs/CFC exhibits superior catalytic activity with an overpotential of 240 mV at 10 mA cm-2 toward OER, and the onset potential of 0.92 V for ORR. Moreover, utilization of CoNi@N-CNTs/CFC in liquid and solid-state ZABs exhibited exceptional stability, manifesting a consistent cycling operation lasting for 100 and 15 h, respectively.

Se-functionalized metal-free catalysts rich in sp3-hybridized carbon enable efficient oxygen electroreduction.

Carbon-based metal-free materials are emerging as leading candidates to replace noble-metal catalysts in the oxygen reduction reaction (ORR). Herein, we introduce a facile secondary carbonation technique for fabricating Se and N co-doped metal-free catalysts using a zeolite imidazole framework (ZIF-8) as the precursor. The optimal electrocatalyst, designated SeNC-900, exhibited good ORR performance under both alkaline and acidic conditions, with half-wave potentials of 0.864 V and 0.731 V (vs. RHE), respectively. Density functional theory (DFT) calculations reveal that the enhanced activity of SeNC-900 originates from Se doping, which triggers an increase in the intrinsic defects of sp3-hybridized C. Concurrently, the sp3-hybridized C, in concert with Se dopant, modulates the electronic structure of the active C atoms. This work not only underscores the significance of tuning the electronic structure to boost catalytic performance by enriching intrinsic defects but also presents a fresh insight into the effect of heteroatom doping on carbon-based materials for electrocatalysis.

Chitosan pyrolysis in the presence of a ZnCl2/NaCl salts for carbons with electrocatalytic activity in oxygen reduction reaction in alkaline solutions.

The one-step carbonization of low cost and abundant chitosan biopolymer in the presence of salt eutectics ZnCl2/NaCl results in nitrogen-doped carbon nanostructures (8.5 wt.% total nitrogen content). NaCl yields the spacious 3D structure, which allows external oxygen to easily reach the active sites for the oxygen reduction reaction (ORR) distinguished by their high onset potential and the maximum turnover frequency of 0.132 e site⁻1 s⁻1. Data show that the presence of NaCl during the synthesis exhibits the formation of pores having large specific volumes and surface (specific surface area of 1217 m2 g-1), and holds advantage by their pores characteristics such as their micro-size part, which provides a platform for mass transport distribution in three-dimensional N-doped catalysts for ORR. It holds benefit over sample pre-treated with LiCl in terms of the micropores specific volume and area, seen as their percentage rate, measured in the BET. Therefore, the average concentration of the active site on the surface is larger.

Efficacy and safety of PARPis combined with an ICIs for advanced or metastatic triple-negative breast cancer: a single-arm meta-analysis.

Although the intervention for triple-negative breast cancer (TNBC) patients has improved and survival time has increased, the combination of immune checkpoint inhibitors(ICIs) and PARP inhibitors (Poly ADP-Ribose Polymerase inhibitors, PARPis) is still controversial. Previous studies revealed that the combined use of ICIs and PARPis led to increased antitumor activity. However, most of these combined regimens are nonrandomized controlled trials with small sample sizes. The purpose of this meta-analysis was to evaluate the efficacy and safety of ICIs combined with PARPis in patients with advanced or metastatic TNBC. The PubMed, Embase, Cochrane Library and Web of Science databases were systematically searched. The results including the objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse events (AEs), were subjected to further analysis. Four studies involving 110 subjects were included in this meta-analysis. The combined ORR and DCR were 23.6% and 53.6%, respectively; while the ORR and DCR of BRCAmut patients were 38.1% and 71.4%, respectively. The median PFS of the patients was 4.29 months. As for safety, the most common AEs were nausea (49.0%), anemia (44.3%) and fatigue (40.6%). Most of them were grade 1 or 2, and the incidence of adverse events ≥ III was obviously low. Except for anemia, the incidence of AEs ≥ III was < 10%. This meta-analysis revealed that the combination of ICIs and PARPis has good efficacy and safety for advanced or metastatic TNBC patients.

Spin Manipulation of Heterogeneous Molecular Electrocatalysts by an Integrated Magnetic Field for Efficient Oxygen Redox Reactions.

Understanding the spin-dependent activity of nitrogen-coordinated single metal atom (M-N-C) electrocatalysts for oxygen reduction and evolution reactions (ORR and OER) remains challenging due to the lack of structure-defined catalysts and effective spin manipulation tools. Herein, both challenges using a magnetic field integrated heterogeneous molecular electrocatalyst prepared by anchoring cobalt phthalocyanine (CoPc) deposited carbon black on polymer-protected magnet nanoparticles, are addressed. The built-in magnetic field can shift the Co center from low- to high-spin (HS) state without atomic structure modification, affording one-order higher turnover frequency, a 50% increased H2O2 selectivity for ORR, and a ≈4000% magnetocurrent enhancement for OER. This catalyst can significantly minimize magnet usage, enabling safe and continuous production of a pure H2O2 solution for 100 h from a 100 cm2 electrolyzer. The new strategy demonstrated here also applies to other metal phthalocyanine-based catalysts, offering a universal platform for studying spin-related electrochemical processes.

Correlative Effects of Carbon Support Structures and Surface Properties on ORR Catalytic Activities of Loaded Catalysts.

As a complex three-phase heterogeneous catalyst, the oxygen reduction reaction (ORR) catalyst activity is determined by the interfacial and surface structures and chemical state of the catalyst support. As a typical biomass carbon-based support, rice husk-based porous carbon (RHPC) has natural unique hierarchical porous structures, which easily regulate the microstructure and surface properties. This study explored the correlative effects of RHPC structure and surface properties on ORR catalytic activity through the typical modification methods, namely, alkali etching, high temperature, oxidation, and ball milling. The various factors for the joint effects are defined as the specific surface area, oxygen-containing functional groups, graphite edge defects, resistivity, and contact angle. The analysis of such joint influences is difficult to quantitatively evaluate due to the large number of experimental factors and small sample sizes. Partial least-squares (PLS) can better deal with such problems. Therefore, a PLS regression model was established to evaluate the relative weight of each factor on the catalytic activity for the RHPC-based support catalysts. The results reveal that the regression coefficients of four factors yield similar magnitude for the effect of the half-wave potential (E1/2). However, graphite edge defects had a more significant impact on the limiting diffusion current density (J) and electron transfer number (n). Furthermore, an optimal support named BM-RHPC-3 was prepared with more defects and oxygen-containing functional groups, which prepared Fe-NS/BM-RHPC-3 presenting the best ORR catalytic activity (E1/2 = 0.880 V, J of 5.15 mA cm-2), superior to Pt/C (E1/2 = 0.844 V, J of 4.99 mA cm-2). The statistical regression model is validated with a relative error of less than 5% between predicted and true values for analyzing RHPC-based ORR catalysts' catalytic performance. It shows the feasibility of experiment-informed learning for data-driven material discovery and design.

Acidic and Alkaline pH Controlled Oxygen Reduction Reaction Pathway over Co-N4C Catalyst.

Enhanced oxygen reduction reaction (ORR) kinetics and selectivity are crucial to advance energy technologies like fuel cells and metal-air batteries. Single-atom catalysts (SACs) with M-N4/C structure have been recognized to be highly effective for ORR. However, the lack of a comprehensive understanding of the mechanistic differences in the activity under acidic and alkaline environments is limiting the full potential of the energy devices. Here, a porous SAC is synthesized where a cobalt atom is coordinated with doped nitrogen in a graphene framework (pCo-N4C). The resulting pCo-N4C catalyst demonstrates a direct 4e- ORR process and exhibits kinetics comparable to the state-of-the-art (Pt/C) catalyst. Its higher activity in an acidic electrolyte is attributed to the tuned porosity-induced hydrophobicity. However, the pCo-N4C catalyst displays a difference in ORR activity in 0.1 m HClO4 and 0.1 m KOH, with onset potentials of 0.82 V and 0.91 V versus RHE, respectively. This notable activity difference in acidic and alkaline media is due to the protonation of coordinated nitrogen, restricted proton coupled electron transfer (PCET) at the electrode/electrolyte interface. The effect of pH over the catalytic activity is further verified by Ab-initio molecular dynamics (AIMD) simulations using density functional theory (DFT) calculations.

Deepening the Understanding of Carbon Active Sites for ORR Using Electrochemical and Spectrochemical Techniques.

Defect-containing carbon nanotube materials were prepared by subjecting two commercial multiwalled carbon nanotubes (MWCNTs) of different purities to purification (HCl) and oxidative conditions (HNO3) and further heat treatment to remove surface oxygen groups. The as-prepared carbon materials were physicochemically characterized to observe changes in their properties after the different treatments. TEM microscopy shows morphological modifications in the MWCNTs after the treatments such as broken walls and carbon defects including topological defects. This leads to both higher surface areas and active sites. The carbon defects were analysed by Raman spectroscopy, but the active surface area (ASA) and the electrochemical active surface area (EASA) values showed that not all the defects are equally active for oxygen reduction reactions (ORRs). This suggests the importance of calculating either ASA or EASA in carbon materials with different structures to determine the activity of these defects. The as-prepared defect-containing multiwalled carbon nanotubes exhibit good catalytic performance due to the formation of carbon defects active for ORR such as edge sites and topological defects. Moreover, they exhibit good stability and methanol tolerances. The as-prepared MWCNTs sample with the highest purity is a promising defective carbon material for ORR because its activity is only related to high concentrations of active carbon defects including edge sites and topological defects.

Effect of Strain Engineering on the Spin State of the Ni-N4/C Single-Atom Catalyst and Its Consequence in Electrocatalysis.

Strain engineering is an effective strategy to improve the activity of catalysts, especially for flexible carbon-based materials. Nitrogen-coordinated single atomic metals on a carbon skeleton (M-Nx/C) are of interest in catalytic electroreduction reactions due to their high activity and atomic utilization. However, the effect of strain on the structure-activity relationship between the electrochemical activity and the electronic and geometric structures of Ni-Nx/C remains unclear. Here, we found that by applying tensile strain on the Ni-N4/C, the spin state of the single atom can be changed from a low-spin to a high-spin state. Moreover, the energy gap between the highest occupied d orbital of Ni and the lowest unoccupied molecular orbital of the adsorbed species narrowed. With an increasing strain rate, the catalytic activity of O2 and CO2 electroreduction can be improved. Especially for the 2e- O2 reduction, the implicit solvent model, constant-potential method, and microkinetic model were used to verify the positive effect of suitable stretching on the catalytic activity from thermodynamic and kinetic viewpoints. This work can reveal the relationship between strain, spin state, and the catalytic activity of Ni-Nx/C.

Rational Construction of Cyanide-Functionalized D-A-π-D Covalent Organic Framework for Highly Efficient Overall H2O2 Photosynthesis from Air and Water.

Sacrificial-agent-free overall photosynthesis of H2O2 from water and air represents currently a promising route to reform the industrial anthraquinone production manner, but, still blocks by the requirement of pure O2 feedstock, due to the insufficient oxygen supply from water under air. Herein, we report a rational molecule design on COFs (covalent organic frameworks) equiped with cyanide-functionalized D-A-π-D system for highly efficient overall H2O2 production from air and water through photocatalytic oxygen reduction reactions (ORR) and water oxidation reaction (WOR). Without using any sacrificial agent, the as-synthesized D-A-π-D COF is found to enable a H2O2 production rate as high as 4742 µmol h-1 g-1 from water and air and an O2 utilization and conversion rate up to 88%, exceeding the other D-A-π-A COF by respectively 1.9- and 1.3-fold. Such high performance is attributed to the tuned electronic structure and prolonged charge lifetime facilitated by the unique D-A-π-D structure and cyanide groups. This work highlights a fundamental molecule design on advanced photocatalytic COFs with complicated D-A system for low-cost and massive H2O2 production.

Promoting Electrocatalytic Oxygen Reactions Using Advanced Heterostructures for Rechargeable Zinc-Air Battery Applications.

In order to facilitate electrochemical oxygen reactions in electrically rechargeable zinc-air batteries (ZABs), there is a need to develop innovative approaches for efficient oxygen electrocatalysts. Due to their reliability, high energy density, material abundance, and ecofriendliness, rechargeable ZABs hold promise as next-generation energy storage and conversion devices. However, the large-scale application of ZABs is currently hindered by the slow kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). However, the development of heterostructure-based electrocatalysts has the potential to surpass the limitations imposed by the intrinsic properties of a single material. This Account begins with an explanation of the configurations of ZABs and the fundamentals of the oxygen electrochemistry of the air electrode. Then, we summarize recent progress with respect to the variety of heterostructures that exploit bifunctional electrocatalytic reactions and overview their impact on ZAB performance. The range of heterointerfacial engineering strategies for improving the ORR/OER and ZAB performance includes tailoring the surface chemistry, dimensionality of catalysts, interfacial charge transfer, mass and charge transport, and morphology. We highlight the multicomponent design approaches that take these features into account to create advanced highly active bifunctional catalysts. Finally, we discuss the challenges and future perspectives on this important topic that aim to enhance the bifunctional activity and performance of zinc-air batteries.

Precisely Designed Morphology and Surface Chemical Structure of Fe-N-C Electrocatalysts for Enhanced Oxygen Reaction Reduction Activity.

Fe-N-C materials have been regarded as one of the potential candidates to replace traditional noble-metal-based electrocatalysts for the oxygen reduction reaction (ORR). It is believed that the structure of carbon support in Fe-N-C materials plays an essential role in highly efficient ORR. However, precisely designing the morphology and surface chemical structure of carbon support remains a challenge. Herein, we present a novel synthetic strategy for the preparation of porous carbon spheres (PCSs) with high specific surface area, well-defined pore structure, tunable morphology and controllable heteroatom doping. The synthesis involves Schiff-based polymerization utilizing octaaminophenyl polyhedral oligomeric silsesquioxane (POSS-NH2) and heteroatom-containing aldehydes, followed by pyrolysis and HF etching. The well-defined pore structure of PCS can provide the confinement field for ferroin and transform into Fe-N-C sites after carbonization. The tunable morphology of PCS can be easily achieved by changing the solvents. The surface chemical structure of PCS can be tailored by utilizing different heteroatom-containing aldehydes. After optimizing the structure of PCS, Fe-N-C loading on N,S-codoped porous carbon sphere (NSPCS-Fe) displays outstanding ORR activity in alkaline solution. This work paves a new path for fabrication of Fe-N-C materials with the desired morphology and well-designed surface chemical structure, demonstrating significant potential for energy-related applications.

Enhancing Oxygen Reduction Reaction of Single-Atom Catalysts by Structure Tuning.

Deciphering the fine structure has always been a crucial approach to unlocking the distinct advantages of high activity, selectivity, and stability in single-atom catalysts (SACs). However, the complex system and unclear catalytic mechanism have obscured the significance of exploring the fine structure. Therefore, we endeavored to develop a three-component strategy to enhance oxygen reduction reaction (ORR), delving deep into the profound implications of the fine structure, focusing on central atoms, coordinating atoms, and environmental atoms. Firstly, the mechanism by which the chemical state and element type of central atoms influence catalytic performance is discussed. Secondly, the significance of coordinating atoms in SACs is analyzed, considering both the number and type. Lastly, the impact of environmental atoms in SACs is reviewed, encompassing existence state and atomic structure. Thorough analysis and summarization of how the fine structure of SACs influences the ORR have the potential to offer valuable insights for the accurate design and construction of SACs.

Fluid-Induced Piezoelectric Field Enhancing Photo-Assisted Zn-Air Batteries Based on a Fe@P(V-T) Microhelical Cathode.

Photo-assisted Zn-air batteries can accelerate the kinetics of oxygen reduction and oxygen evolution reactions (ORR/OER); however, challenges such as rapid charge carrier recombination and continuous electrolyte evaporation remain. Herein, for the first time, piezoelectric catalysis is introduced in a photo-assisted Zn-air battery to improve carrier separation capability and accelerate the ORR/OER kinetics of the photoelectric cathode. The designed microhelical catalyst exploits simple harmonic vibrations to regenerate the built-in electric field continuously. Specifically, in the presence of the low-frequency kinetic energy that occurs during water flow, the piezoelectric-photocoupling catalyst of poly(vinylidene fluoride-co-trifluoroethylene)@ferric oxide(Fe@P(V-T)) is periodically deformed, generating a constant reconfiguration of the built-in electric field that separates photogenerated electrons and holes continuously. Further, on exposure to microvibrations, the gap between the charge and discharge potentials of the Fe@P(V-T)-based photo-assisted Zn-air battery is reduced by 1.7 times compared to that without piezoelectric assistance, indicating that piezoelectric catalysis is highly effective for enhancing photocatalytic efficiency. This study provides a thorough understanding of coupling piezoelectric polarization and photo-assisted strategy in the field of energy storage and opens a fresh perspective for the investigation of multi-field coupling-assisted Zn-air batteries.

Layered Porous Ring-Like Carbon Network Protected FeNi Metal Atomic Pairs for Bifunctional Oxygen Electrocatalysis and Rechargeable Zn-Air Batteries.

Bimetallic atom catalysts exhibit ultra-high oxygen electrocatalytic activity by harnessing mutual promotion and synergistic effects between adjacent metal active centers, surpassing the performance of single metal atomic catalysts. Herein, FeNi atom pairs protected by hierarchical porous annular carbon grids (P-FeNi-NPC) are introduced using a mediator-assisted MOFs-derived strategy. The introduction of the multi-block copolymer P123 ensures the uniform confinement and dispersion of metal ions, followed by thermal decomposition to form a "planetary-ring-like" carbon framework that anchors the bimetallic atomic pairs in the active region. The homogeneous distribution of adjacent Fe-N4 and Ni-N4 active sites significantly enhances catalytic activity and stability. Leveraging unique electronic and geometric structures, the resulting P-FeNi-NPC catalyst demonstrates exceptional ORR and OER activities with an ΔE value of 0.705 (E1/2 = 0.845 V, Ej = 10 = 1.55 V). Theoretical calculations unveil that FeNi bimetallic sites loaded on nitrogen-doped carbon frameworks with specific curvature effectively modulate the energy of d-band centers, thus balancing the free energy of oxygen-containing intermediates. This study presents a novel and versatile approach for synthesizing advanced bifunctional catalysts, poised to drive the future development of Zn-air batteries.

Directional Construction of Low-Coordination Fe-N3 Coupled with Intrinsic Carbon Defects for High-Efficiency Oxygen Reduction.

Regulating the coordination environment of Fe-Nx sites is an efficient but challenging approach for promoting the intrinsic catalytic activity of single-atom Fe/N-codoped carbon (Fe-N-C) toward the oxygen reduction reaction (ORR). Herein, low-coordination Fe-N3 sites coupled with carbon vacancies (Fe-N3/CV) are directionally constructed in Fe-N-C via pyrolysis of a metal-organic framework (MOF) precursor with N3-Zn-O-Fe moieties, which are delicately prefabricated by chemically anchoring Fe3+ onto a H2O-etching induced linker-missing Zn-N3 site in the MOF precursor. The optimized Fe-N-C with the Fe-N3/CV sites displays a high ORR half-wave potential of 0.92 V (vs RHE), which is attributed to the optimized electronic structure and binding strengths of the active Fe center toward the ORR intermediates stemming from the synergy of the asymmetric configuration of Fe-N3 as well as the adjacent carbon vacancies. This work could be enlightening for the design and construction of high-activity coupling sites in metal and nitrogen-codoped carbon catalysts.

Enhanced durability of Pd/CeO2-C via metal-support interaction for oxygen reduction reaction.

It is a challenge to improve the long-term durability of Pd-based electrocatalysts for oxygen reduction reaction (ORR) in fuel cells. Herein, Pd/CeO2-C-T (T= 800 °C, 900 °C and 1000 °C) hybrid catalysts with metal-support interaction are prepared from Ce-based metal organic framework precursor. Abundant tiny CeO2nanoclusters are produced to form nanorod structures with uniformly distributed carbon through a calcination process. Meanwhile, both carbon and CeO2nanoclusters have good contact with the following deposited surfactant-free Pd nanoclusters. Benefited from the large specific surface area, good conductivity and structure integrity, Pd/CeO2-C-900 exhibits the best electrocatalytic ORR performance: onset potential of 0.968 V and half-wave potential of 0.857 V, outperforming those obtained on Pd/C counterpart. In addition, the half-wave potential only shifts 7 mV after 6000 cycles of accelerated durability testing, demonstrating robust durability.

Factors associated with oocyte recovery rates during in-vitro fertilization among Nigerian women.

Introduction: the availability of oocytes is fundamental to in vitro fertilization (IVF). The factors associated with optimal or suboptimal oocyte recovery rates (ORR) in low-resource settings are not well known. This study aimed to determine the factors associated with ORR by comparing demographic and IVF cycle data of women undergoing IVF in our Centre. Methods: this was a prospective study of 110 infertile women undergoing IVF at Nisa Premier Hospital, Abuja Nigeria, from October 2020 to September 2021. All women had reached the stage of oocyte retrieval or further, after receiving ovarian stimulation with our routine protocols. Treatment was monitored by serial transvaginal ultrasonography. The oocyte retrieval procedures were performed under conscious sedation, 36 hours after the ovulatory trigger. Optimal ORR was when eggs were obtained from at least 80% of follicles punctured. Sub-optimal ORR was when it was less than 80%. Data analyses utilized SPSS statistical software and a p-value of < 0.05 was considered significant. Results: the mean age of all women was 34.1±4.9 years. Sixty-nine women (62.7%) had sub-optimal ORR while 41 (37.3%) had optimal ORR. Six women (5.5%) had no oocytes retrieved. Significantly more women with sub-optimal ORR were obese (70.6 vs 29.4%) and had higher follicle-stimulating hormone (FSH) levels (8.11 vs 6.34 miu/ml), p-value- 0.039. Women with sub-optimal ORR had higher mean prolactin levels (17.10 ± 13.93 miu/ml) than women with optimal ORR 11.43 ± 6.65 miu/ml), p-value- 0.019). Significantly more oocytes (5.99 vs 10.37, p-value 0.001), and MII oocytes (5.78 vs 7.56, p-value 0.035) were retrieved in women with optimal than sub-optimal ORR. The duration of stimulation, total amounts of gonadotropins administered, and fertilized oocytes were not significantly different among both groups (p-value >0.05). Conclusion: this study has shown the factors associated with ORR in our setting to be basal FSH, prolactin, and obesity.

Fluorine-doped Carbon Support Enables Superfast Oxygen Reduction Kinetics by Breaking the Scaling Relationship.

It is well-established that Pt-based catalysts suffer from the unfavorable linear scaling relationship (LSR) between *OOH and *OH (ΔG(*OOH) = ΔG(*OH) + 3.2 ± 0.2 eV) for the oxygen reduction reaction (ORR), resulting in a great challenge to significantly reduced ORR overpotentials. Herein, we propose a universal and feasible strategy of fluorine-doped carbon supports, which optimize interfacial microenvironment of Pt-based catalysts and thus significantly enhance their reactive kinetics. The introduction of C-F bonds not only weakens the *OH binding energy, but also stabilizes the *OOH intermediate, resulting in a break of LSR. Furthermore, fluorine-doped carbon constructs a local super-hydrophobic interface that facilitates the diffusion of H2O and the mass transfer of O2. Electrochemical tests show that the F-doped carbon-supported Pt catalysts exhibit over 2-fold higher mass activities than those without F modification. More importantly, those catalysts also demonstrate excellent stability in both rotating disk electrode (RDE) and membrane electrode assembly (MEA) tests. This study not only validates the feasibility of tuning the electrocatalytic microenvironment to improve mass transport and to break the scaling relationship, but also provides a universal catalyst design paradigm for other gas-involving electrocatalytic reactions.

Real-world efficacy of low dose osimertinib as second-line treatment in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer.

Background: Response rates of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) to lower doses of osimertinib [20 mg once daily (OD) and 40 mg OD] are similar to those of the recommended dose of 80 mg OD, but there is a lack of real-world evidence on the effect of the lower doses of osimertinib on survival outcomes. We conducted this study to assess the efficacy and safety of lower osimertinib doses for patients with EGFR-mutated advanced NSCLC whose disease had progressed on earlier generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world clinical practice. Methods: This multicenter, retrospective study included patients with EGFR-mutated advanced NSCLC treated with low doses of osimertinib after failing first- or second-generation EGFR TKIs due to acquired T790M mutation. Data on demographics, staging, treatment history, best overall response rate (ORR) based on RECIST 1.1, and adverse events (AEs) were collected from the patients' case notes. Descriptive data were described in percentages and medians. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Of the 22 patients studied [males =8 and females =14; Eastern Cooperative Oncology Group (ECOG) 1 or 2 =7 and ECOG 3 or 4 =15], 45.5% were on 40 mg OD, 31.8% were on 80 mg every other day (EOD), and 22.7% on 40 mg EOD. First-line EGFR TKIs used included afatinib, erlotinib, and gefitinib. The ORR with lower doses of second-line osimertinib was 77.3%. Overall, the median PFS was 10.0 months [95% confidence interval (CI): 8.6-11.4] and median OS was 13.0 months (95% CI: 9.4-16.6). In patients with ECOG 1 or 2, the median PFS was 18.0 months (95% CI: 5.8-30.2) and the median OS was not reached at the time of analysis. In patients with poor ECOG performance status of 3 and 4, good survival outcomes were also seen with a median PFS of 7.0 months (95% CI: 4.7-9.3) and median OS of 10.0 months (95% CI: 7.5-12.5). All AEs except one case of paronychia were Grade 1. There were no Grade 3 or 4 AEs. Conclusions: Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment with first- or second-generation EGFR TKIs due to T790M mutation.