Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial

Emens, Leisha A.; Esteva, Francisco J.; Beresford, Mark; Saura, Cristina; Laurentiis, Michelino De; Kim, Sung‐Bae; Im, Seock Ah; Wang, Yifan; Salgado, Roberto; Mani, Aruna; Shah, Jigna; Lambertini, Chiara; Liu, Haiying; Haas, Sanne L. de; Patre, Monika; Loi, Sherene

doi:10.1016/s1470-2045(20)30465-4

Cited by 272 publications

(242 citation statements)

References 17 publications

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“…The phase II KATE2 study [29] tested the addition of immunotherapy to T-DM1 in HER2positive advanced breast cancer that had progressed after trastuzumab-based treatment. Atezolizumab, an immune checkpoint inhibitor against programmed death-ligand 1 (PD-L1), combined with nanoparticle albumin-bound paclitaxel has demonstrated remarkable activity in PD-L1 positive metastatic triple-negative breast cancer [43].…”

Section: Discussionmentioning

confidence: 99%

“…Atezolizumab, an immune checkpoint inhibitor against programmed death-ligand 1 (PD-L1), combined with nanoparticle albumin-bound paclitaxel has demonstrated remarkable activity in PD-L1 positive metastatic triple-negative breast cancer [43]. However, in KATE2, the addition of atezolizumab to T-DM1 did not present a statistically or clinically meaningful improvement in PFS for PD-L1 non-selective population, but PD-L1 positive patients had clinically longer PFS (8.5 months versus 4.1 months) [29]. Other studies concerning immunotherapy of HER2-positive advanced breast cancer suggested that PD-L1 positive population could derive benefit from immune checkpoint inhibitors [44,45].…”

Section: Discussionmentioning

confidence: 99%

“…Due to the limitations of treatments comparisons, we divided the PFS analysis into two parts. The first part involved 8 treatments in 9 studies [15,16,20,22,24,[26][27][28][29] and we referred it as PFS (#1) and the second part included 3 treatments in 2 studies [30,31] and we referred it as PFS (#2). In terms of OS, we analyzed 7 treatments in 7 studies [15,16,18,21,23,25,29].…”

Section: Network Meta-analysesmentioning

confidence: 99%

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Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis

Chen¹,

Chen²,

Lv³

et al. 2021

J. Cancer

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Purpose: Different second-line treatments of patients with trastuzumab-resistant human epidermal growth factor receptor 2 (HER2) positive breast cancer were examined in randomized controlled trials (RCTs). A network meta-analysis is helpful to evaluate the comparative survival benefits of different options. Methods: We performed a bayesian network meta-analysis using R-4.0.0 software and fixed consistency model to compare the progression free survival (PFS) and overall survival (OS) benefits of different second-line regimens. Results: 13 RCTs (19 publications, 4313 patients) remained for qualitative synthesis and 12 RCTs (17 publications, 4022 patients) were deemed eligible for network meta-analysis. For PFS, we divided network analysis into two parts owing to insufficient connections among treatments. The first part involved 8 treatments in 9 studies and we referred it as PFS (#1). Amid the following 8 interventions: pyrotinib + capecitabine, T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, T-DM1, trastuzumab + capecitabine, lapatinib + capecitabine, neratinib, and capecitabine, we found consistent benefits between the first three interventions; moreover, pyrotinib + capecitabine was most likely to be associated with the best benefits; capecitabine monotherapy was associated with the worst PFS. The second part included 3 treatments in 2 studies and we referred it as PFS (#2): everolimus + trastuzumab + vinorelbine had better PFS benefits versus trastuzumab + vinorelbine and afatinib + vinorelbine. For OS, we analyzed 7 treatments in 7 studies, and observed T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, and T-DM1 had similar effectiveness, and the first had the highest probability to yield the longest OS; capecitabine or neratinib alone yielded the worst OS benefits. Conclusions: Our work comprehensively summarized and analyzed current available RCT-based evidence of the second-line treatments for trastuzumab-treated, HER2-positive, advanced breast cancer. These results provide clinicians and oncologists meaningful references for clinical drug administration and the development of novel effective therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Network Meta-analysesmentioning

confidence: 99%

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Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis

Chen¹,

Chen²,

Lv³

et al. 2021

J. Cancer

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“…In addition, the main focus of IO development in BC has been put in TNBC due to its general enrichment of TILs and the lack of effective therapies other than chemotherapy. Although the use of IO agents in other subsets of BC, such as luminal B tumors or pretreated HER2-positive BC, has also been explored, there is still much controversy on its use in those settings [21][22][23]. It is still unclear whether a better design based on a more accurate selection and less pretreated patients would have led to positive results.…”

Section: Which Are the Current Challenges With Io?mentioning

confidence: 99%

Lights and Shadows in Immuno-Oncology Drug Development

Sirvén

Pernas

Cheang

2021

Cancers

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The rapidly evolving landscape of immuno-oncology (IO) is redefining the treatment of a number of cancer types. IO treatments are becoming increasingly complex, with different types of drugs emerging beyond checkpoint inhibitors. However, many of the new drugs either do not progress from phase I-II clinical trials or even fail in late-phase trials. We have identified at least five areas in the development of promising IO treatments that should be redefined for more efficient designs and accelerated approvals. Here we review those critical aspects of IO drug development that could be optimized for more successful outcome rates in all cancer types. It is important to focus our efforts on the mechanisms of action, types of response and adverse events of these novel agents. The use of appropriate clinical trial designs with robust biomarkers of response and surrogate endpoints will undoubtedly facilitate the development and subsequent approval of these drugs. Further research is also needed to establish biomarker-driven strategies to select which patients may benefit from immunotherapy and identify potential mechanisms of resistance.

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“…Thus, the diagnosis and treatment of BC have gotten stuck in a bottleneck. Surprisingly, immune checkpoint inhibitors were proven to function on some certain subpopulation of BC (4,5). Atezolizumab, a programmed death 1 ligand (PD-L1) inhibitor, was suggested to prolong of overall survival (OS) in advanced triple-negative BC (TNBC) patients whose PD-L1 expressed positive.…”

Section: Introductionmentioning

confidence: 99%

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Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial

Cited by 272 publications

References 17 publications

Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis

Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis

Lights and Shadows in Immuno-Oncology Drug Development

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