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Background: The combination of platinum-based chemotherapy and an antibody to PD-1 or to its ligand PD-L1, with or without an antibody to CTLA-4, has improved the survival of individuals with metastatic non-small-cell lung cancer (NSCLC). However, no randomised controlled trial has evaluated the survival benefit of adding a CTLA-4 inhibitor to platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor., Methods: This open-label, randomised, phase 3 trial was conducted at 48 hospitals in Japan. Eligible patients were aged 20 years or older with previously untreated advanced NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with known driver oncogenes were excluded. Participants were randomly assigned (1:1) to receive platinum-based chemotherapy (four cycles) plus pembrolizumab (pembrolizumab group) or platinum-based chemotherapy (two cycles) plus nivolumab-ipilimumab (nivolumab-ipilimumab group). The primary endpoint was overall survival and assessed in all randomly assigned patients on an intention-to-treat basis. The trial is registered in the Japan Registry for Clinical Trials, jRCTs031210013, and is now closed to new enrolment and is ongoing., Findings: Between patient accrual initiation on April 6, 2021, and discontinuation of the trial on March 30, 2023, 11 (7%) of 148 patients in the nivolumab-ipilimumab group had a treatment-related death. Because of the high number of treatment-related deaths, patient accrual was terminated early, resulting in 295 patients (236 [80%] male and 59 [20%] female) enrolled; the primary analysis was done on the basis of 117 deaths (fewer than the required 329 deaths). By May 25, 2023 (data cutoff), overall survival did not differ significantly between the nivolumab-ipilimumab group and the pembrolizumab group (median 23·7 months [95% CI 17·6-not estimable] vs 20·5 months [17·6-not estimable], respectively; hazard ratio 0·98 [90% CI 0·72-1·34]; p=0·46). Non-haematological adverse events of grade 3 or worse occurred in 87 (60%) of 146 patients in the nivolumab-ipilimumab group and 59 (41%) of 144 patients in the pembrolizumab group. The pembrolizumab group tended to have a better quality of life compared with the nivolumab-ipilimumab group., Interpretation: The safety and efficacy data suggest an unfavourable benefit-risk profile for nivolumab-ipilimumab combined with platinum-based chemotherapy relative to pembrolizumab combined with platinum-based chemotherapy as a first-line treatment for patients with advanced NSCLC, although a definitive conclusion awaits an updated analysis of overall survival., Funding: The National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development., Competing Interests: Declaration of interests YoS has received grants from Chugai Pharmaceutical; and personal fees from Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Taiho Pharmaceutical, and Kyowa Kirin, all outside of the submitted work. ShN has received grants from AstraZeneca, Chugai Pharmaceutical, and MSD; consulting fees from Asahi Kasei Pharma; and personal fees from AstraZeneca, Bayer, Chugai Pharmaceutical, Asahi Kasei Pharma, Kyowa Hakko Bio, and MSD, all outside of the submitted work. SS has received grants from AnHeart Therapeutics, AstraZeneca, Chugai Pharmaceutical, MSD, Daiichi Sankyo, Bristol Myers Squibb, Nippon Boehringer Ingelheim, Ono Pharmaceutical, AbbVie, Amgen, Taiho Pharmaceutical, Takeda, Accerise, and Parexel International; and personal fees from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly, Novartis, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, Towa Pharmaceutical, Sysmex, and Eisai, all outside of the submitted work. HidehH has received research fundings from MSD, AbbVie, AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Janssen, Chugai Pharmaceutical, and Roche; personal fees from AstraZeneca, MSD, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Roche, Amgen, and Abbvie; and personal fees from AstraZeneca, Chugai Pharmaceutical, Roche, Ono Pharmaceutical, Bristol Myers Squibb, and AbbVie (served on the advisory board), all outside of the submitted work. YaY has received personal fees from Taiho Pharmaceutical and Takeda, all outside of the submitted work. HidetH has received grants from IQVIA Services Japan, Eisai, Syneos Health Clinical, EP-CRSU, EPS, Shionogi, Nippon Kayaku, Otsuka Pharmaceutical, Takeda, GSK, MSD, Sanofi, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Bristol Myers Squibb, SRL Medisearch, Janssen Pharmaceutical, PRA Health Sciences, CMIC, Astellas Pharma, Pfizer R&D Japan, Ascent Development Services, Labcorp Development Japan, Eisai, Kobayashi Pharmaceutical, Bayer, and Pfizer Japan; royalties or licenses from Sysmex; personal fees from Ono Pharmaceutical, Merck, Daiichi Sankyo, 3H Clinical Trial, AstraZeneca, Novartis Pharma, Chugai Pharmaceutical, Bristol Myers Squibb, Eli Lilly Japan, Amgen, MSD, Sysmex, Pfizer Japan, Takeda, Nippon Boehringer Ingelheim; and personal fees for serving on an advisory board from Daiichi Sankyo, Nippon Boehringer Ingelheim, AstraZeneca, Amgen, Chugai Pharmaceutical, Novocure, Eli Lilly Japan, Gilead Science, and Blueprint Medicine, all outside of the submitted work. KA has received lecture fees from AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, MSD, Bristol Myers Squibb, and Takeda, all outside of the submitted work. SN has received grants from GSK, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, Teijin, Kyowa Kirin, Shionogi, Boehringer Ingelheim, Daiichi Sankyo, Kyorin, and Nippon Kayaku; personal fees from AstraZeneca, Pfizer, Chugai Pharmaceutical, Eli Lilly, Daiichi Sankyo, MSD, Ono Pharmaceutical, Eisai, Kyorin, Taiho Pharmaceutical, Takeda, Boehringer Ingelheim, Novartis, Amgen, Merck, Nippon Kayaku, and Kyowa Kirin; and personal fees for serving on advisory boards from AstraZeneca and Daiichi Sankyo, all outside of the submitted work. RM has received personal fees from Daiichi Sankyo, Chugai Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Eli Lilly Japan, MSD, Amgen, and Merck; and personal fees for serving on an advisory board from Daiichi Sankyo, all outside of the submitted work. MY has received grants from Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Taiho Pharmaceutical, and Takeda; and personal fees from AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Johnson & Johnson, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer Japan, and Taiho Pharmaceutical, all outside of the submitted work. TY has received grants from MSD, Chugai Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim Japan, Takeda, Delta-Fly Pharma, Janssen, AbbVie, Daiichi Sankyo, and Parexel International; and personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Pfizer Japan, Bristol Myers Squibb, Ono Pharmaceutical, Takeda, Nippon Kayaku, MSD, Novartis, and Merck, all outside of the submitted work. KY has received grants from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Lilly, MSD, Pfizer, Taiho Pharmaceutical, and Takeda; and personal fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Janssen, Kyowa Kirin, Lilly, Merck Serono, Novartis, Ono Pharmaceutical, Otsuka, Taiho Pharmaceutical, and Takeda, all outside of the submitted work. TakayK has received grants from AstraZeneca, Amgen, MSD, Janssen, Takeda, and Daiichi Sankyo; and personal fees from AstraZeneca, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, MSD, Pfizer, and Nippon Kayaku, all outside of the submitted work. HO has received grants from Bristol Myers Squibb, MSD, and Taiho Pharmaceutical, all outside of the submitted work. TakasK has received personal fees from MSD, AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, and Bristol Myers Squibb, all outside of the submitted work. KK has received personal fees from AstraZeneca, MSD, Chugai Pharmaceutical, Eli Lilly Japan, and Taiho Pharmaceutical; payment for expert testimony from Eli Lilly Japan; and personal fees for serving on advisory boards from Eli Lilly Japan and AstraZeneca, all outside of the submitted work. YF has received personal fees from AstraZeneca, Amgen, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and Taiho Pharmaceutical; payment for expert testimony from Chiome Bioscience, Otsuka Pharmaceutical, and Ono Pharmaceutical; and personal fees for serving on advisory boards from AstraZeneca, Daiichi Sankyo, Micron, and Ono Pharmaceutical, all outside of the submitted work. SM has received grants from AstraZeneca, Takeda, Chugai Pharmaceutical, Sanofi, MSD, Daiichi Sankyo, Ono Pharmaceutical, and Janssen; and personal fees from AstraZeneca, Chugai Pharmaceutical, Takeda, Eli Lilly, MSD, Pfizer, Novartis, and Taiho Pharmaceutical, all outside of the submitted work. SK has received personal fees from Boehringer Ingelheim Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, MSD, Ono Pharmaceutical, and Guardant Health Japan, all outside of the submitted work. HA reports grants from Amgen and Chugai Pharmaceutical; personal fees from Amgen, AstraZeneca, Boehringer Ingelheim Japan, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and Taiho Pharmaceutical; personal fees for serving on advisory boards from Amgen, MSD, Janssen, and Sandoz; and a role on the WCLC Patient Advocacy Committee, all outside of the submitted work. HK has received grants from Eli Lilly; and personal fees from Chugai Pharmaceutical, AstraZeneca, MSD, Bristol Myers Squibb, Novartis, Eli Lilly Japan, Ono Pharmaceutical, and Takeda, all outside of the submitted work. ToshiK has received grants from Chugai Pharmaceutical, AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Kyowa Hakko Kirin, Merck, Daiichi Sankyo, Amgen, AbbVie, Sanofi, Eisai, Labcorp Development Japan, IQVIA Services Japan, Gilead Sciences, Pfizer, and Bayer; consulting fees from Chugai Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Pfizer Japan, Daiichi Sankyo, Bayer, and AbbVie; and personal fees from Chugai Pharmaceutical, AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Pfizer Japan, Kyowa Hakko Kirin, Nippon Boehringer Ingelheim, Merck, Nippon Kayaku, Novartis, Daiichi Sankyo, Takeda, Bayer, Sawai, Amgen, and Eisai, all outside of the submitted work. HF has received grants from the National Cancer Center Research and Development Fund; and lecture fees from Kyowa Kirin, Chugai Pharmaceutical, and CMIC, all outside of the submitted work. YO reports grants from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, LOXO, Kirin, Sumitomo, Pfizer, Taiho Pharmaceutical, Novartis, Takeda, Kissei, Daiichi Sankyo, and Janssen; personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Hakko Kirin, Eisai, and Daiichi Sankyo; payment for expert testimony from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics, and PharmaMar; personal fees for serving on an advisory board from Haihe Biopharma; and roles in the Japanese Society of Medical Oncology, Japan Lung Cancer Society, and Japan Clinical Oncology Group, all outside of the submitted work. IO has received grants from the National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development during the conduct of the study; grants from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD, Eli Lilly, Astellas, Bristol Myers Squibb, Novartis, Chugai Pharmaceutical, Pfizer, and AbbVie; consulting fees from AstraZeneca, Bristol Myers Squibb, and AbbVie; and personal fees from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD, Eli Lilly, Bristol Myers Squibb, Novartis, Chugai Pharmaceutical, and Pfizer, all outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: Disclosure Daisuke Shibahara reports a funding grant from Eli Lilly Japan KK. Yoshimasa Shiraishi reports a funding grant from Chugai Pharmaceutical Co Ltd, and speaking and lecture fees from Ono Pharmaceutical Co Ltd, Bristol-Myers Squibb Co, AstraZeneca Pharmaceuticals LP, Taiho Pharmaceutical Co Ltd, Chugai Pharmaceutical Co Ltd, and Kyowa Kirin. Eiji Iwama reports speaking and lecture fees from Chugai Pharmaceutical Co Ltd and AstraZeneca Pharmaceuticals LP. Kentaro Tanaka reports speaking and lecture fees from AstraZeneca Pharmaceuticals LP, Chugai Pharmaceutical Co Ltd, Ono Pharmaceutical Co Ltd, Bristol-Myers Squibb Co, MSD, Novartis Pharmaceuticals, Eli Lilly Japan KK, Daiichi Sankyo Co Ltd, Pfizer, Merck and Co Inc, and Takeda Pharmaceutical Co Ltd. Isamu Okamoto reports funding grants from Chugai Pharmaceutical Co Ltd, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Co Ltd, Merck and Co Inc, Takeda Pharmaceutical Co Ltd, Eli Lilly Japan KK, Ono Pharmaceutical Co Ltd, Bristol-Myers Squibb Co, Taiho Pharmaceutical Co Ltd, and Nippon Boehringer Ingelheim Co Ltd, and speaking and lecture fees from Chugai Pharmaceutical Co Ltd, AstraZeneca Pharmaceuticals LP, Takeda Pharmaceutical Co Ltd, Eli Lilly Japan KK, Ono Pharmaceutical Co Ltd, Bristol-Myers Squibb Co, Taiho Pharmaceutical Co Ltd, Nippon Boehringer Ingelheim Co Ltd, and Novartis Pharmaceuticals.

Background: Osimertinib shows pronounced efficacy for EGFR mutation-positive non-small cell lung cancer (NSCLC) including associated central nervous system (CNS) metastases. Tumors inevitably develop resistance to the drug, however. Osimertinib is sometimes readministered after completion of standard chemotherapy. To clarify which patients might receive benefit from osimertinib readministration, we have retrospectively assessed its efficacy with a focus on CNS metastases., Methods: A retrospective analysis of medical records was performed for 21 patients who underwent osimertinib readministration at Kyushu University Hospital between March 2016 and April 2023. CNS metastases were evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST)., Results: Among the 21 enrolled patients, 16 individuals had target lesions on the basis of RECIST. One (6.3%) of these 16 patients achieved a partial response to osimertinib readministration, with the remaining 15 patients showing stable or progressive disease. The median overall progression-free survival (PFS) and median overall survival for all 21 patients were 3.8 and 13.9 months, respectively. The efficacy of osimertinib readministration for CNS metastases was evaluable in eight patients including five individuals with leptomeningeal metastases. The objective response rate for CNS metastases and the improvement rate for leptomeningeal metastases were both 100%. The median PFS with regard to CNS or non-CNS lesions for these eight patients was 24.7 and 10.5 months, respectively., Conclusions: Osimertinib readministration showed limited efficacy for non-CNS lesions but excellent efficacy for CNS metastases, suggesting that such treatment is an option for EGFR-mutated NSCLC patients with CNS metastases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:E Iwama received honoraria from Chugai Pharmaceutical, Thermo Fisher Scientific and AstraZeneca. Y Shiraishi received from Chugai Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, AstraZeneca, and Bristol Myers Squibb. K Tanaka received honoraria from Nippon Kayaku, Nippon Boehringer Ingelheim, Chugai Pharmaceutical, and Japan Society for the Promotion of Science. I Okamoto received honoraria and research funding from Chugai Pharmaceutical, AstraZeneca, Daiichi Sankyo, Merck & Co Inc, Takeda Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Taiho Pharmaceutical and Nippon Boehringer Ingelheim. I Okamoto received honoraria from Novartis Pharmaceuticals. The remaining authors declare no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Mechanisms underlying the growth and survival of non-small cell lung cancer (NSCLC) cells positive for activating mutations of the epidermal growth factor receptor gene (EGFR) have remained unclear. We here examined the functional relation between such mutant forms of EGFR and Yes-associated protein (YAP), a transcriptional coactivator of the Hippo signaling pathway that regulates cell proliferation and survival. Under the condition of serum deprivation, epidermal growth factor (EGF) induced activation of YAP in NSCLC cell lines positive for mutated EGFR but not in those wild type (WT) for EGFR. Similar EGF-induced activation of YAP was apparent in A549 lung cancer cells forcibly expressing mutant EGFR but not in those overexpressing the WT receptor. Furthermore, EGF induced apoptotic cell death in serum-deprived A549 cells overexpressing the WT form of EGFR but not in those expressing mutant EGFR, and knockdown of YAP rendered the latter cells sensitive to this effect of EGF. Our results thus suggest that activation of YAP mediates resistance of EGFR-mutated NSCLC cells to EGF-induced apoptosis and thereby contributes specifically to the survival of such cells., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kentaro Tanaka reports financial support was provided by Nippon Kayaku Co Ltd. Kentaro Tanaka reports financial support was provided by Nippon Boehringer Ingelheim Co Ltd. Kentaro Tanaka reports financial support was provided by Chugai Pharmaceutical Co Ltd. Kentaro Tanaka reports financial support was provided by Japan Society for the Promotion of Science. Isamu Okamoto reports a relationship with Chugai Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with AstraZeneca Pharmaceuticals LP that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with Daiichi Sankyo Co Ltd that includes: funding grants. Isamu Okamoto reports a relationship with Merck & Co Inc that includes: funding grants. Isamu Okamoto reports a relationship with Takeda Pharmaceutical Company Limited that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with Eli Lilly Japan KK that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with Ono Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with Bristol-Myers Squibb Co that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with Taiho Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with Nippon Boehringer Ingelheim Co Ltd that includes: funding grants and speaking and lecture fees. Isamu Okamoto reports a relationship with Novartis Pharmaceuticals that includes: speaking and lecture fees., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The PACIFIC regimen of consolidation therapy with the programmed cell death-ligand 1 inhibitor durvalumab after definitive concurrent chemoradiation therapy has become a standard of care for individuals with unresectable stage III NSCLC. Nevertheless, approximately half of the treated patients experience disease progression within 1 year, with the mechanisms of treatment resistance being poorly understood. We here performed a nationwide prospective biomarker study to explore the resistance mechanisms (WJOG11518L:SUBMARINE)., Methods: A total of 135 patients with unresectable stage III NSCLC who received the PACIFIC regimen were included for comprehensive profiling of the tumor microenvironment by immunohistochemistry, transcriptome analysis, and genomic sequencing of pretreatment tumor tissue and flow cytometric analysis of circulating immune cells. Progression-free survival was compared on the basis of these biomarkers., Results: The importance of preexisting effective adaptive immunity in tumors was revealed for treatment benefit regardless of genomic features. We also identified CD73 expression by cancer cells as a mechanism of resistance to the PACIFIC regimen. Multivariable analysis of immunohistochemistry data with key clinical factors as covariables indicated that low CD8 + tumor-infiltrating lymphocyte density and the high CD73 + cancer cells were independently associated with poor durvalumab outcome (hazard ratios = 4.05 [95% confidence interval: 1.17-14.04] for CD8 + tumor-infiltrating lymphocytes; 4.79 [95% confidence interval: 1.12-20.58] for CD73). In addition, whole-exome sequencing of paired tumor samples suggested that cancer cells eventually escaped immune pressure as a result of neoantigen plasticity., Conclusions: Our study emphasizes the importance of functional adaptive immunity in stage III NSCLC and implicates CD73 as a promising treatment target, thus providing insight forming a basis for development of a new treatment approach in NSCLC., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRAS G12C . We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRAS G12C mutation who had been previously treated with other anticancer drugs., Methods: We conducted a randomised, open-label phase 3 trial at 148 centres in 22 countries. We recruited patients aged at least 18 years with KRAS G12C -mutated advanced NSCLC, who progressed after previous platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Key exclusion criteria included new or progressing untreated brain lesions or symptomatic brain lesions, previously identified oncogenic driver mutation other than KRAS G12C for which an approved therapy is available (eg EGFR or ALK), previous treatment with docetaxel (neoadjuvant or adjuvant docetaxel was allowed if the tumour did not progress within 6 months after the therapy was terminated), previous treatment with a direct KRAS G12C inhibitor, systemic anticancer therapy within 28 days of study day 1, and therapeutic or palliative radiation therapy within 2 weeks of treatment initiation. We randomly assigned (1:1) patients to oral sotorasib (960 mg once daily) or intravenous docetaxel (75 mg/m 2 once every 3 weeks) in an open-label manner using interactive response technology. Randomisation was stratified by number of previous lines of therapy in advanced disease (1 vs 2 vs >2), ethnicity (Asian vs non-Asian), and history of CNS metastases (present or absent). Treatment continued until an independent central confirmation of disease progression, intolerance, initiation of another anticancer therapy, withdrawal of consent, or death, whichever occurred first. The primary endpoint was progression-free survival, which was assessed by a blinded, independent central review in the intention-to-treat population. Safety was assessed in all treated patients. This trial is registered at ClinicalTrials.gov, NCT04303780, and is active but no longer recruiting., Findings: Between June 4, 2020, and April 26, 2021, 345 patients were randomly assigned to receive sotorasib (n=171 [50%]) or docetaxel (n=174 [50%]). 169 (99%) patients in the sotorasib group and 151 (87%) in the docetaxel group received at least one dose. After a median follow-up of 17·7 months (IQR 16·4-20·1), the study met its primary endpoint of a statistically significant increase in the progression-free survival for sotorasib, compared with docetaxel (median progression-free survival 5·6 months [95% CI 4·3-7·8] vs 4·5 months [3·0-5·7]; hazard ratio 0·66 [0·51-0·86]; p=0·0017). Sotorasib was well tolerated, with fewer grade 3 or worse (n=56 [33%] vs n=61 [40%]) and serious treatment-related adverse events compared with docetaxel (n=18 [11%] vs n=34 [23%]). For sotorasib, the most common treatment-related adverse events of grade 3 or worse were diarrhoea (n= 20 [12%]), alanine aminotransferase increase (n=13 [8%]), and aspartate aminotransferase increase (n=9 [5%]). For docetaxel, the most common treatment-related adverse events of grade 3 or worse were neutropenia (n=13 [9%]), fatigue (n=9 [6%]), and febrile neutropenia (n=8 [5%])., Interpretation: Sotorasib significantly increased progression-free survival and had a more favourable safety profile, compared with docetaxel, in patients with advanced NSCLC with the KRAS G12C mutation and who had been previously treated with other anticancer drugs., Funding: Amgen., Competing Interests: Declaration of interests AJdL reports financial interests, institutional, research grant from BMS, MSD, Boehringer, AstraZeneca; non-financial interests, other from Merck Serono, Roche. MLJ reports financial interests, institutional, research grant from AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda Therapeutics, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics, Black Diamond, Carisma Therapeutics, Elicio Therapeutics, EQRx, Immunitas Therapeutics, Kartos Therapeutics, Mirati Therapeutics, Palleon Pharmaceuticals, Rain Therapeutics; financial interests, institutional, consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, IDEAYA Biosciences, iTeos Therapeutics, Janssen, Lilly, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Regeneron Pharmaceuticals, Ribon Therapeutics, Sanofi-Aventis, Turning Point Therapeutics, VBL Therapeutics, Takeda Pharmaceuticals, Arrivant, Pyramid Biosciences, Revolution Medicines, Seagen. JM reports financial interests, personal fees from Amgen, AstraZeneca, Roche, Pierre Fabre, Pfizer; financial interests, institutional, research grant from AstraZeneca, Roche, Pierre Fabre; advisory board for Merck, Roche, AstraZeneca, MSD, BMS, Pfizer, Hengrui Therapeutics, Daiichi, Boehringer, Pierre Fabre, Amgen. A MCD reports other, institutional, advisory board for Amgen, Bayer, Boehringer Ingelheim, Roche, Sanofi; other, institutional, invited speaker for AstraZeneca, Janssen, Eli Lilly, Pfizer, Takeda; financial interests, institutional, research grant from Amgen; financial interests, institutional, principal investigator, local PI for Amgen, Daiichi, JNJ, Eli Lilly, Mirati Therapeutics; financial interests, institutional, principal investigator, coordinating PI for Roche; financial interests, institutional, other, steering committee member for Roche. GM reports financial interests, personal, other, consulting fees from Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; financial interests, personal, other, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; financial interests, personal, other, payment for expert testimony from Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; financial interests, personal, other, support for attending meetings and/or travel from Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; financial interests, personal, other, participation on a data safety monitoring board or advisory board for Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; financial interests, personal, other, leadership or fiduciary role in other board, society, committee or advocacy group, unpaid for European Society for Medical Oncology working groups (Educational Publication Working Group, Adolescents and Young Adults working group); financial interests, institutional, principal investigator for Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Gilead Greece, GSK Greece, Amgen Hellas, Sanofi Greece. MP reports financial interests, personal, advisory board for AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eisei, MSD, Novartis, Pfizer, Roche, Takeda, Merck, Sanofi, Bayer, Amgen; financial interests, personal, other, travel grant from AstraZeneca, BMS, Boehringer Ingelheim, Roche, Takeda, Vifor; financial interests, personal, speaker fees from Janssen, Nestle. JW reports financial interests, personal, advisory board, lectures fees from Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Merck, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda, Turning Point, Nuvalent; financial interests, institutional, research grant from BMS, Janssen, Novartis, Pfizer. MS reports financial interests, institutional, research grant from AstraZeneca, Bristol Myers Squibb; financial interests, personal, consulting fees from Amgen, AstraZeneca, BIOCAD, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda; financial interests, personal, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Novartis; financial interests, personal, support for attending meetings and/or travel from BIOCAD, Bristol Myers Squibb, Boehringer Ingelheim, Janssen, Novartis; financial interests, personal, participation on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, Novartis, Sanofi, GlaxoSmithKline, Merck Serono. HL reports financial interests, other, personal fees from Daiichi Sankyo, AstraZeneca, Pfizer, Novartis, Amgen, MSD, Roche, BMS, Eli Lilly, Boehringer Ingelheim. FS reports financial interests, personal, other, consulting fees from AstraZeneca, Amgen, Novartis, BeiGene Guardant Health, BerGenBio, Navire Pharma, Tango Therapeutics, Calithera Biosciences; financial interests, personal, other, lecture fees from European Society for Medical Oncology, Japanese Lung Cancer Society, Medscape, Intellisphere, VSPO McGill Universite de Montreal, RV Mais Promoção Eventos Ltda, MJH Life Sciences, IDEOlogy Health, MI&T, PER, LLC, CURIO; financial interests, personal, other, fees for travel, food and beverage from Dava Oncology, Tango Therapeutics, American Association for Cancer Research, International Association for the Study of Lung Cancer (IASLC), MJH Life Sciences, IDEOlogy Health, MI&T, PER, LLC, CURIO; financial interests, personal, stocks/shares, stock or stock options for BioNTech SE, Moderna (completed 2020); financial interests, institutional, research grant from Amgen, Mirati Therapeutics, Revolution Medicines, Pfizer, Novartis, Merck & Co; participation on a data safety monitoring board or advisory board for AstraZeneca, Amgen, Novartis, BeiGene, Guardant Health, BerGenBio; Calithera Biosciences. YY reports no relationships to disclose. S-WK reports no relationships to disclose. HL reports financial interests, personal, other, consulting fees from Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Merck, Amgen, Boehringer, Pfizer, Lilly; financial interests, personal, other, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, AbbVie, GSK, Amgen, Boehringer, Pfizer, Lilly; financial interests, personal, other, payment for expert testimony from Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer, Pfizer, Lilly; financial interests, personal, other, support for attending meetings and/or travel from Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Boehringer, Pfizer; financial interests, personal, participation on a data safety monitoring board or advisory board for Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer, Pfizer, Lilly; other, personal, leadership role, W4O Core Committee – Unpaid for European Society for Medical Oncology; other, personal, leadership role, President of the Scientific Committee and Member of the Board of Directors – Unpaid for Hellenic Cooperative Oncology Group; other, personal, leadership role, member of board of directors – unpaid for Hellenic Foundation for Cancer Research, FairLife LCC; Other, personal, leadership role, legal representative member of board of directors - unpaid for W4O-Hellas; financial interests, personal and institutional, principal investigator, pi in sponsored clinical trials, personal and institutional fees from Bristol Myers Squibb, Boehringer Ingelheim, Roche, AbbVie, Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist. SN reports financial interests, personal, advisor/speaker bureau for AstraZeneca, BI, MSD, Roche, Sanofi, Pfizer, Takeda, Thermo Fisher, Novartis; financial interests, personal, speaker bureau for BeiGene. AJvdW reports financial interests, institutional, research grant from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche, Takeda; financial interests, fees to institution from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche, Takeda, Janssen Cilag, Lilly, Amgen, Merck. YC reports other, personal, speaker faculty for Amgen, AstraZeneca, Bristol Myers Squibb, Guardant Health, Jazz Pharmaceuticals, Pfizer, Takeda; other, personal, advisory board for AstraZeneca, Bristol Myers Squibb, Mirati Therapeutics; financial interests, institutional, principal investigator, local PI for Amgen, AstraZeneca, Bristol Myers Squibb, EMD/Serono, Helsinn, Ipsen, Merck. SP reports financial interests, institutional, support for study conduct and medical writing from AstraZeneca; financial interests, institutional, principal investigator, coordinating PI for Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp and Dohme, Roche/Genentech. Financial interests, institutional, consulting fees from AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GlaxoSmithKline, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, PeerView, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody; financial interests, institution, other, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Mirati Therapeutics, Novartis, PeerView, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda; financial interests, institutional, other, support for attending meetings and/or travel from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche/Genentech, Takeda; financial interests, institutional, other, participation on a data safety monitoring board or advisory board for AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, PeerView, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody. EF reports financial interests, institutional, research grant from Merck Healthcare KGaA (grant for oncology innovation), Fundación Merck Salud; financial interests, institutional, consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Sanofi, Takeda, BerGenBio; financial interests, institutional, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology; other financial/non-financial interests, board member for Grífols. BJS reports financial interests, institutional, funding, institutional funding for conduct of clinical trial from Amgen; financial interests, personal, advisory board/honoraria from Amgen, Roche-Genentech, Novartis, Pfizer, AstraZeneca, Bristol Myers Squibb, Takeda, Eli Lilly, Merck Sharp Dohme, Janssen. SSR reports financial interests, personal, research grant from Amgen, AstraZeneca; financial interests, personal, advisory board for AstraZeneca, Mirati Therapeutics, Merck, BMS, GlaxoSmithKline, Genmab. CD reports no relationships to disclose. CL reports financial interests, personal, advisory board from Amgen; financial interests, personal, educational presentation/workshop from Amgen; financial interests, institutional, advisory board for CBPartners; non-financial interests, institutional, principal investigator, coordinating PI for Amgen, BI, Mirati Therapeutics, Revolution Medicines, Roche; non-financial interests, institutional, principal investigator, local PI Apollomics. CGF reports financial interests, other, consulting fees from AstraZeneca, Janssen; advisory board for IASCL; financial interests, personal, stocks/shares, stock or stock options in Oncoclínicas - Brazil. NB reports financial interests, other, consulting fees/honoraria from Amgen. CCO, YW, BM, TV, GN, BS report financial interests, personal, current or former full-time employment, employee and stockholder/shareholder in Amgen. DW reports financial interests, personal, invited speaker, advisory event, travel for BMS; financial interests, personal, invited speaker, advisory event for AstraZeneca, Janssen, EMD Serono; financial interests, personal, invited speaker, advisory event, consultant for Amgen, Merck; financial interest, personal, advisory event, consultant for Jazz Pharmaceuticals, Fresenius Kbi; financial interests, personal, advisory event for Pfizer, Mirati Therapeutics, Regeneron/Sanofi; financial interests, personal, advisory event for Exelixis, Eisai, Pfizer, Mirati Therapeutics, Regeneron/Sanofi, Lilly, Sanofi, Astellas, Gilead. LPA reports financial interests, research grant from MSD, AstraZeneca, Pfizer, BMS; financial interests, consulting fees from Lilly, MSD, Roche, PharmaMar, Merck, AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati Therapeutics, GSK, Janssen, Takeda, Daiichi Sankyo; financial interests, payment/honoraria for lectures, presentations, speakers bureau from AstraZeneca, Janssen, Merck, Mirati Therapeutics. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Renal impairment can affect treatment tolerability and outcome in individuals with cancer. We aimed to assess the safety and efficacy of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC) and renal impairment enrolled in a phase 3 trial of nab-paclitaxel vs. docetaxel., Patients and Methods: Previously treated NSCLC patients were randomly allocated (1:1) to receive docetaxel (60 mg/m²) on day 1 or nab-paclitaxel (100 mg/m²) on days 1, 8, and 15 of a 21-day cycle. Safety and efficacy outcomes of treatment were evaluated according to renal function., Results: Among the 503 patients enrolled in the phase 3 trial, 17.3% had moderate renal impairment (creatinine clearance of ≤50 mL/min, n = 49 for docetaxel and n = 38 for nab-paclitaxel) and 53.1% had mild renal impairment (creatinine clearance of >50 to ≤80 mL/min, n = 133 for docetaxel and n = 134 for nab-paclitaxel). For patients with renal impairment, the incidence of febrile neutropenia was lower in the nab-paclitaxel group than in the docetaxel group. The difference in treatment efficacy for nab-paclitaxel vs. docetaxel among patients with moderate or mild renal impairment was similar to that among the overall study population., Conclusion: Nab-paclitaxel was found to be tolerable and beneficial for previously treated patients with advanced NSCLC and mild or moderate renal impairment., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: To evaluate the efficacy and safety of osimertinib plus bevacizumab for previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations., Methods: We conducted a randomized, open-label, phase 2 study at 21 institutions in Japan. Previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations received either osimertinib (80 mg, daily) plus bevacizumab (15 mg/kg, every 3 wk) or osimertinib monotherapy, and were stratified according to sex, stage, and EGFR mutation status. The primary end point was progression-free survival (PFS) in the intention-to-treat population, assessed by means of blinded, independent central radiologic review., Results: Between January 2018 and September 2018, a total of 122 patients were enrolled (osimertinib + bevacizumab arm, 61 patients; osimertinib monotherapy arm, 61 patients). At a median follow-up duration of 19.8 months, the median PFS was 22.1 months for osimertinib plus bevacizumab and 20.2 months for osimertinib monotherapy, with a hazard ratio of 0.862 (60% confidence interval: 0.700-1.060, 95% confidence interval: 0.531-1.397, one-sided stratified log-rank p = 0.213). Adverse events of grade 3 or worse were observed in 34 patients (56%) in the osimertinib plus bevacizumab arm and 29 (48%) in the osimertinib monotherapy arm. In addition, two (3%) and 11 patients (18%) experienced any grade pneumonitis, respectively, and grade 3 pneumonitis was observed in one patient (2%) in each arm., Conclusions: This study failed to exhibit the efficacy of osimertinib plus bevacizumab for improving the PFS among patients with nonsquamous NSCLC harboring EGFR mutations as first-line treatment., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to evaluate the efficacy and safety of nanoparticle albumin-bound (nab-) paclitaxel for previously treated patients with advanced NSCLC., Methods: In this randomized, open-label, noninferiority phase 3 trial, we enrolled patients with advanced NSCLC previously treated with cytotoxic chemotherapy. Patients were randomly allocated (1:1) to receive docetaxel (60 mg/m 2 ) on day 1 or nab-paclitaxel (100 mg/m 2 ) on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival (OS) analyzed on an intention-to-treat basis., Results: Between May 22, 2015, and March 12, 2018, a total of 503 patients were randomly allocated to the treatment. Median OS was 16.2 months (95% confidence interval [CI]: 14.4-19.0) for the 252 patients allocated to nab-paclitaxel and 13.6 months (95% CI: 10.9-16.5) for the 251 patients allocated to docetaxel (hazard ratio = 0.85, 95.2% CI: 0.68-1.07). Median progression-free survival was 4.2 months (95% CI: 3.9-5.0) for the nab-paclitaxel group versus 3.4 months (95% CI: 2.9-4.1) for the docetaxel group (hazard ratio = 0.76, 95% CI: 0.63-0.92, p = 0.0042). The objective response rate was 29.9% (95% CI: 24.0-36.2) for the nab-paclitaxel group and 15.4% (95% CI: 10.9-20.7) for the docetaxel group (p = 0.0002). Adverse events of grade greater than or equal to 3 included febrile neutropenia (5 of 245 patients [2%] in the nab-paclitaxel group versus 55 of 249 patients [22%] in the docetaxel group) and peripheral sensory neuropathy (24 [10%] versus 2 [1%], respectively)., Conclusions: Nab-paclitaxel was noninferior to docetaxel in terms of OS. It should, thus, be considered a standard treatment option for previously treated patients with advanced NSCLC., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The British Thoracic Society guidelines for diagnostic flexible bronchoscopy (FB) in adults recommend that intravenous sedation should be offered to patients undergoing bronchoscopy. However, it is difficult to determine the adequate depth of sedation for each patient because of inter-individual variability., Methods: This prospective, open-label, single-arm study was conducted in patients undergoing routine bronchus examination with FB. All patients underwent FB under local anesthesia and conscious sedation, with initial administration of 0.03 mg/kg midazolam. The sedation level during FB was objectively assessed using the Ramsay sedation score (RSS). Two hours after the procedure, patients completed a questionnaire about its efficacy and adverse effects using a visual analog scale (VAS). Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal RSS that could improve the subjective efficacy indicated by the VAS., Results: This study enrolled 110 consecutive patients between September 2008 and February 2012. The median total amount of midazolam administered was 1.65 mg per patient. In an analysis of ROC curves between RSS and VAS, the area under the ROC curve for an RSS of 4 against the others was 0.66 (95% CI: 0.54 to 0.77, p = 0.014). The area under the ROC curve was not shown to be statistically significant for RSSs other than 4., Conclusions: The optimal depth of conscious sedation during FB for conventional examination was achieved at an RSS of 4. The patients' subjective evaluations indicated that a deep level of conscious sedation does not seem necessary for FB., (Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Nanoparticle albumin-bound (nab) paclitaxel is a promising new therapeutic agent for all histologic types of non-small-cell lung cancer (NSCLC). We recently performed a phase 2 study of weekly nab-paclitaxel in patients with previously treated advanced NSCLC, finding promising activity and acceptable toxicity for this regimen. We have now designed a randomized phase 3 intergroup study (J-AXEL, UMIN000017487) to examine the clinical benefit and safety of nab-paclitaxel compared to docetaxel in patients with previously treated advanced NSCLC., Patients and Methods: Patients are randomized to receive either docetaxel (60 mg/m 2 on day 1 every 3 weeks, control arm) or nab-paclitaxel (100 mg/m 2 on days 1, 8, and 15 every 3 weeks, experimental arm), with each drug being administered until disease progression or unacceptable toxicity. The study will evaluate the noninferiority of nab-paclitaxel relative to docetaxel for the primary end point of overall survival., Conclusion: If the primary objective is achieved, this study will provide evidence for a new alternative treatment option for patients with previously treated advanced NSCLC., (Copyright © 2016 Elsevier Inc. All rights reserved.)