IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase III study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC

Cappuzzo, Federico; McCleod, Michael; Hussein, Maen; Morabito, Alessandro; Rittmeyer, Achim; Conter, Henry Jacob; Kopp, Hans‐Georg; Daniel, Davey B.; McCune, Steven L.; Mekhail, Tarek; Zer, Alona; Reinmuth, Niels; Sadiq, Ahad A.; Archer, Venice; Lohmann, Tania Ochi; Wang, L.; Kowanetz, Marcin; Lin, Wei-Hsin; Sandler, A.; West, Howard

doi:10.1093/annonc/mdy424.065

Cited by 60 publications

(96 citation statements)

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“…These characteristics include tumors with EGFR mutation, which exhibit weaker immunogenicity, less abundant immune cell infiltration in the tumor microenvironment and lower responsiveness to ICI monotherapy . This finding echoes recent results from the IMpower 130 trial in which the population with EGFR and ALK driver mutations did not receive a boost in treatment efficacy from the addition of ICIs; the IMpower 150 trial showed that only the administration of bevacizumab significantly improved the treatment efficacy of ICIs in such patients . Consistent with these findings, our results also showed that patients in the EGFR mutation subgroup who received single agent ICI treatment exhibited the shortest PFS (Fig b).…”

Section: Discussionsupporting

confidence: 89%

“…An earlier study focusing on patients with high PD-L1 expression showed that pembrolizumab improved treatment efficacy over a platinum-doublet, 5 whereas this effect was not fully reproduced in the equivalent backdrop of high PD-L1 expression in the Keynote 042 study. 23 Similar variations were also noted in a nivolumab study, in which nivolumab monotherapy showed higher efficacy over a platinum- doublet only in a subgroup of patients with a high tumor mutation burden (TMB) 24 The differential efficacy associated with histology has been noted previously. 3,4 Overall, these findings suggest that a durable effect of single agent ICIs did occur in a small subset of patients who can only be partially identified by PD-L1 and TMB biomarkers.…”

Section: Discussionsupporting

confidence: 63%

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Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non‐small cell lung cancer

et al. 2019

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Background Single agent immune checkpoint inhibitors (ICIs) improve survival outcomes compared to chemotherapy for advanced non‐small cell lung cancer (NSCLC), but treatment efficacy widely varies. The combination of ICIs with chemotherapy has shown promising efficacy over chemotherapy alone; however, whether this strategy is superior to single agent ICIs for the treatment of advanced NSCLC remains unknown. Methods The records of 109 patients with advanced NSCLC who were administered at least one cycle of ICIs were retrospectively reviewed. Patients were grouped based on the presence or absence of a chemotherapy treatment combination. Efficacy and survival outcomes were analyzed. Result Sixty‐nine (58.0%) patients received single agent ICIs (ICI group) and 50 (42.0%) received ICIs and chemotherapy (ICC group). The median (3.2 vs. 3.0 months; P = 0.025) and one‐year (34.5 vs. 9.6%; P = 0.026) progression‐free survival (PFS) rates were significantly better in the ICC than in the ICI group. The superior efficacy of ICC remained in the propensity score matched pairs (median PFS 3.2 vs. 2.6 months, P = 0.032; 1‐year PFS 35.2 vs. 7.6%; P = 0.035). Eastern Cooperative Oncology Group performance status 0–1 (HR 0.37, 95% CI 0.22–0.62; P < 0.001) and the ICC group (HR 0.56, 95% CI 0.34–0.94; P = 0.028) were predictive of PFS. Subgroup‐to‐chemotherapy interaction revealed improved risk reduction for adenocarcinoma and EGFR mutation. Conclusion Combing chemotherapy with ICIs improved treatment efficacy over ICIs alone. The additional efficacy of chemotherapy may differ between histological subtypes and EGFR mutation status.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 63%

Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non‐small cell lung cancer

et al. 2019

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“…Results of IMpower130 presented at the ESMO 2018 Congress showed that the study met its coprimary end points of longer OS and PFS with atezolizumab plus chemotherapy (consisting of carboplatin and nab-paclitaxel) versus chemotherapy alone in the first-line treatment of patients with stage IV nonsquamous NSCLC with no EGFR or ALK alterations. Addition of atezolizumab to chemotherapy increased the median OS from 13.9 to 18.6 months (HR: 0.79; 95% CI: 0.64-0.98; p = 0.033) and the median PFS from 5.5 to 7.0 months (HR: 0.64; 95% CI: 0.54-0.77; p < 0.001) [41]. Results of IMpower132 demonstrated that addition of atezolizumab to carboplatin or cisplatin plus pemetrexed as first-line therapy significantly prolonged PFS (HR: 0.60; 95% CI: 0.49-0.72; p < 0.001) in patients with stage IV nonsquamous NSCLC.…”

Section: First-line Treatmentmentioning

confidence: 99%

Nivolumab plus Ipilimumab in Non–Small-Cell Lung Cancer

Kim

Shin

2020

N Engl J Med

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Nivolumab and ipilimumab, two therapeutic immune checkpoint inhibitor antibodies that block PD-1 and CTLA-4, respectively, have indications in cancer as single agents and in combination. In this Review, we examine the potential role of dual immune checkpoint inhibition with nivolumab plus ipilimumab in the management of patients with previously untreated advanced non-small-cell lung cancer, based on results from the Phase III CheckMate 227 study. Immunotherapies with indications in the first-line treatment of non-small-cell lung cancer include pembrolizumab alone and combined with chemotherapy, and atezolizumab combined with bevacizumab and chemotherapy. CheckMate 227 is the first Phase III study evaluating first-line chemotherapy-sparing combination immunotherapy and including tumor mutational burden as a biomarker for patient selection.Lung cancer is the most commonly diagnosed cancer and the leading cause of death from cancer worldwide, accounting for an estimated 18.4% of all cancer-related deaths in 2018 [1]. In the USA, lung cancer has the second highest age-adjusted incidence among primary cancer types (after breast cancer) and is associated with by far the highest cancer-related mortality [2]. Global, age-standardized incidence rates for lung cancer are lower among women than men across all regions; however, high rates among women are seen in North America, Northern and Western Europe, and Australia/New Zealand [1]. Of an estimated 222,500 new cases of lung cancer in the USA in 2017, almost half (47%) were diagnosed in women [3]. Non-small-cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases in the USA [4]. Although smoking is the most common cause of NSCLC, approximately 10-15% of patients with NSCLC have never smoked [5].Until a few years ago, the treatment for patients with advanced NSCLC with no known targetable driver mutations was essentially limited to systemic cytotoxic therapy, with platinum doublet chemotherapy as the standard first-line treatment. In randomized controlled trials, platinum-based therapies were associated with a median overall survival (OS) of 10-13 months and 2-year survival rates of 17-24% from the time of treatment initiation [6][7][8][9][10][11]. Patients who experienced disease progression during first-line therapy had few remaining treatment options, including docetaxel, erlotinib, gefitinib or pemetrexed for nonsquamous NSCLC and docetaxel, erlotinib or gefitinib for squamous NSCLC. The recent introduction of immune checkpoint inhibitors [12] has greatly improved outcomes in many cancers, including NSCLC. Therapeutic antibodies that disrupt the interaction between PD-1 and PD-L1, in other words, PD-1 and PD-L1 inhibitors, are now the preferred second-line treatment option after first-line chemotherapy [13,14]. Furthermore, the PD-1 inhibitor pembrolizumab has been approved as monotherapy for the first-line treatment of patients with advanced NSCLC and high PD-L1 expression (tumor proportional score ≥50%) [15,16]. To provide effective first-line treatment optio...

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“…In patients with metastatic NSCLC of nonsquamous histology, three studies have shown an overall survival (OS) benefit from adding an anti-PD-1/PD-L1 antibody to standard chemotherapy: KEYNOTE-189, IMpower150, and IMpower130 (19)(20)(21).…”

Section: Immuno-oncology In Combination With Chemotherapy: Nonsquamoumentioning

confidence: 99%

Immunotherapy for the First-Line Treatment of Patients with Metastatic Non–Small Cell Lung Cancer

Martı́nez¹,

Peters

Stammers³

et al. 2019

Clinical Cancer Research

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Immunotherapy has fundamentally changed the treatment landscape for many patients with cancer. mAbs targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 immune checkpoints have received regulatory approval across a wide range of tumor types, including non-small cell lung cancer (NSCLC). Indeed, treatment approaches for a majority of patients with newly diagnosed metastatic NSCLC are evolving rapidly. Only for the small proportion of patients with metastatic NSCLC and genomicdriven tumors with EGFR or anaplastic lymphoma kinase (ALK)-sensitizing mutations (5%-15%), and possibly BRAF mutations and ROS rearrangements, have initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the preferred therapy. For the remaining patients, an immunotherapy-based regimen alone or in combination with chemotherapy is now the preferred option based on high-level evidence obtained from randomized controlled trials and in accordance with all available guidelines. Deciding between therapeutic options can be difficult due to the lack of direct cross-comparison studies, differences in chemotherapies and stratification factors, and differences in study populations resulting from inclusion criteria such as histology, PD-L1 expression, or tumor mutational burden (TMB). In an attempt to aid the decision-making process, we discuss and summarize the most recent data from studies using immunotherapies for the treatment of patients with previously untreated metastatic NSCLC.

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IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase III study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC

Cited by 60 publications

References 0 publications

Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non‐small cell lung cancer

Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non‐small cell lung cancer

Nivolumab plus Ipilimumab in Non–Small-Cell Lung Cancer

Immunotherapy for the First-Line Treatment of Patients with Metastatic Non–Small Cell Lung Cancer

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