First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study

Lee, Siow Ming; Schulz, Christian; Prabhash, Kumar; Kowalski, Dariusz M.; Szczęsna, Aleksandra; Han, Baohui; Rittmeyer, Achim; Talbot, Toby; Vicente, David; Califano, Raffaele; Le, Anh‐Tuan; Huang, Dingzhi; Liu, Geoffrey; Cappuzzo, Federico; Contreras, Jessica Reyes; Reck, Martin; Palmero, R.; Mak, Milena Perez; Hu, Youyou; Morris, Stefanie; Höglander, Elen; Connors, Mary M.; Biggane, Alice M; Vollan, Hans Kristian Moen; Peters, Solange

doi:10.1016/s0140-6736(23)00774-2

Cited by 46 publications

(29 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding suggests that reduced‐dose chemotherapy combined with PD‐1/PD‐L1 inhibitors can produce synergistic effects in patients with NSCLC. Furthermore, compared with single‐agent chemotherapy, the IPSOS study showed that first‐line treatment with atezolizumab provided a survival benefit and reduced toxicity in NSCLC patients ineligible for platinum‐based chemotherapy without EGFR or ALK alterations 24 . The median OS in the reduced‐dose group in our study was similar to that in the atezolizumab monotherapy group in the IPSOS study (15 vs. 10.3 months).…”

Section: Discussionsupporting

confidence: 69%

“…Furthermore, compared with single-agent chemotherapy, the IPSOS study showed that first-line treatment with atezolizumab provided a survival benefit and reduced toxicity in NSCLC patients ineligible for platinum-based chemotherapy without EGFR or ALK alterations. 24 The median OS in the reduced-dose group in our study was similar to that in the atezolizumab monotherapy group in the IPSOS study (15 vs. 10.3 months). However, the IPSOS study reported a lower incidence of grade 3-4 toxicity compared with our study (16% vs. 27.78%).…”

supporting

confidence: 81%

See 1 more Smart Citation

Efficacy and safety of reduced‐dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real‐world observational study

Ouyang,

Liu,

Liu

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

BackgroundRecently, chemotherapy plus immunotherapy has achieved remarkable efficacy in lung squamous cell carcinoma (LUSC). However, some patients, especially frail people, cannot tolerate full‐dose chemotherapy in the real world. To reduce toxicity, appropriate dose reduction in chemotherapy is necessary. Therefore, this study aimed to demonstrate the efficacy and safety of reduced‐dose chemotherapy plus immunotherapy in LUSC patients in the real world.MethodsA real‐world observational study was conducted concerning patients who received chemotherapy plus immunotherapy in our situation. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were progression‐free survival (PFS), overall survival (OS), and toxicity.ResultsBetween December 2018 and January 2022, 110 patients were enrolled, of whom 54 patients were chemotherapy reduced‐dose group and 56 patients were chemotherapy standard‐dose group. The ORR in the reduced‐dose group is similar to standard‐dose group (85.19% vs. 71.43%, p = 0.082). Similar DCR were observed (100% vs. 94.64%, p = 0.086). Median PFS was 12 months in the reduced‐dose group and standard‐dose group, respectively. Median OS was 15 months and 16 months in the reduced‐dose group and standard‐dose group, respectively. We reported a lower incidence of grade 3–4 toxicity in the reduced‐dose group compared with standard‐dose group (27.78% vs. 42.86%, p = 0.100). The major toxic reactions were better alleviated in the reduced‐dose group than in the standard‐dose group, especially in the thrombocytopenia (p = 0.044), peripheral nerve damage (p = 0.001), gastrointestinal reactions (p < 0.0001), and fatigue (p = 0.001).ConclusionsThe modified regimen with attenuated doses of chemotherapy in combination with immunotherapy was effective and well tolerated in patients with LUSC. The efficacy of this modified regimen is similar to that of the full‐dose regimen.

show abstract

Section: Discussionsupporting

confidence: 69%

supporting

confidence: 81%

Efficacy and safety of reduced‐dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real‐world observational study

Ouyang,

Liu,

Liu

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

show abstract

“…ICIs have been proved its antitumor immunity [ 63 , 64 ]. Clinically, atezolizumab and sintilimab showed improved OS, quality of life, and a favorable safety profile in NSCLC [ 65 , 66 ]. Besides, nivolumab plus ipilimumab showed durable long-term efficacy in advanced NSCLC [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

NGEF is a potential prognostic biomarker and could serve as an indicator for immunotherapy and chemotherapy in lung adenocarcinoma

Chen,

Zhang,

et al. 2024

BMC Pulm Med

View full text Add to dashboard Cite

Background Neuronal guanine nucleotide exchange factor (NGEF) plays a key role in several cancers; however, its role in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to evaluate the efficacy of NGEF as a prognostic biomarker and potential therapeutic target for LUAD. Methods NGEF expression data for multiple cancers and LUAD were downloaded from multiple databases. The high- and low-NGEF expression groups were constructed based on median NGEF expression in LUAD samples, and then performed Kaplan–Meier survival analysis. Differentially expressed genes (DEGs) from the two NGEF expression groups were screened and applied to construct a protein-protein interaction network. The primary pathways were obtained using gene set enrichment analysis. The associations between NGEF expression and clinical characteristics, immune infiltration, immune checkpoint inhibitors (ICIs), sensitivity to chemotherapy, and tumor mutation burden (TMB) were investigated using R. Levels of NGEF expression in the lung tissue was validated using single-cell RNA sequencing, quantitative polymerase chain reaction (qPCR), immunohistochemical staining, and western blot analysis. Results The expression of NGEF mRNA was upregulated in multiple cancers. mRNA and protein expression levels of NGEF were higher in patients with LUAD than in controls, as validated using qPCR and western blot. High NGEF expression was an independent prognostic factor for LUAD and was associated with advanced tumor stage, large tumor size, more lymph node metastasis, and worse overall survival (OS). A total of 182 overlapping DEGs were screened between The Cancer Genome Atlas and GSE31210, among which the top 20 hub genes were identified. NGEF expression was mainly enriched in the pathways of apoptosis, cell cycle, and DNA replication. Moreover, elevated NGEF expression were associated with a high fraction of activated memory CD4+ T cells and M0 macrophages; elevated expression levels of the ICIs: programmed cell death 1 and programmed cell death 1 ligand 1 expression; higher TMB; and better sensitivity to bortezomib, docetaxel, paclitaxel, and parthenolide, but less sensitivity to axitinib and metformin. Conclusion NGEF expression is upregulated in LUAD and is significantly associated with tumor stages, OS probability, immune infiltration, immunotherapy response, and chemotherapy response. NGEF may be a potential diagnostic and prognostic biomarker and therapeutic target in LUAD.

show abstract

“…There is paucity of prospective data to guide the optimal treatment of advanced cancer in patients with poor performance status (ECOG 2-3) or advanced age ≥70 years), highlighting the importance of shared decision making regarding implementation of guideline-recommended care. 1,58 These special populations of patients are often routinely excluded or underrepresented from clinical trials but recently published data from three prospective RCTs 73,74,75 has evaluated the safety and efficacy of single agent and combination immune checkpoint inhibition in this patient population. The IPSOS study is a phase III, global, randomized trial that evaluated first line anti-PD-L1 therapy with atezolizumab versus single agent chemotherapy (vinorelbine or gemcitabine) in investigator-determined platinum ineligible, EGFR/ALK-mutation negative advanced NSCLC with poor performance status (ECOG 2-3) or advanced age (≥70 years) with good performance status (ECOG 0-1) but substantial comorbidities or contraindications to platinum doublet therapy.…”

Section: Special Population (Multiple Chronic Conditions Poor Perform...mentioning

confidence: 99%

“…However certain limitations in the study design, such as lack of a defined criteria for platinum ineligibility, and a weaker comparison arm with single agent chemotherapy may affect the broader applicability of the results in clinical practice. 74 Additionally, a sub cohort of the Checkmate 817 trial evaluated the safety and efficacy of dual check point inhibitor front-line therapy with flat dose PD-1 inhibitor nivolumab (240mg every 2 weeks) with CTLA-4 inhibitor ipilimumab in NSCLC patients with either a poor performance status or good performance status with certain comorbidities (untreated asymptomatic brain metastasis, renal impairment, hepatic impairment, or controlled HIV infection). The results of the study suggested that dual ICI therapy was well tolerated but associated with inferior outcomes in this population of patients, likely due to poor prognosis associated with the underlying disease.…”

Section: Special Population (Multiple Chronic Conditions Poor Perform...mentioning

confidence: 99%

Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3

Jaiyesimi,

Leighl,

Ismaila

et al. 2024

JCO

View full text Add to dashboard Cite

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See complete disclaimer in Appendix 1 and Appendix 2 for more. Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline . PURPOSE To provide evidence-based recommendations for patients with stage IV non–small cell lung cancer (NSCLC) without driver alterations. METHODS This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Ten new RCTs were identified in the latest search of the literature to date. RECOMMENDATIONS Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients without driver alterations. Additional information is available at www.asco.org/living-guidelines .

show abstract

First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study

Cited by 46 publications

References 28 publications

Efficacy and safety of reduced‐dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real‐world observational study

Efficacy and safety of reduced‐dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real‐world observational study

NGEF is a potential prognostic biomarker and could serve as an indicator for immunotherapy and chemotherapy in lung adenocarcinoma

Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3

Contact Info

Product

Resources

About