Atezolizumab in metastatic triple-negative breast cancer: IMpassion130 and 131 trials - how to explain different results?

Franzoi, Maria Alice; Azambuja, Evandro de

doi:10.1136/esmoopen-2020-001112

Cited by 39 publications

(33 citation statements)

References 12 publications

(16 reference statements)

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“…Furthermore, the addition of durvalumab to nab-paclitaxel followed by epirubicin/cyclophosphamide administration as neoadjuvant treatment did not have the same degree of benefit [ 40 ]. Similar conflicting findings have been reported for the combination of atezolizumab with different agents, such as nab-paclitaxel and paclitaxel, for the treatment of metastatic disease [ 41 ]. As in the metastatic setting, many RCTs are currently being conducted to evaluate the therapeutic efficacy of IC inhibitors used in combination with anticancer agents in the neoadjuvant and partially adjuvant settings [ 42 , 43 ].…”

Section: Induction Of Antitumor Immunity After Neoadjuvant and Adjsupporting

confidence: 73%

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

Kim¹,

Kin

2021

Cancers

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The treatment of primary breast cancer has evolved over the past 50 years based on the concept that breast cancer is a systemic disease, with the escalation of adjuvant and neoadjuvant therapies and de-escalation of breast cancer surgery. Despite the development of these therapies, recurrence with distant metastasis during the 10 years after surgical treatment is observed, albeit infrequently. Recent advances in genomic analysis based on circulating tumor cells and circulating tumor DNA have enabled the development of targeted therapies based on genetic mutations in residual tumor cells. A paradigm shift involving the application of neoadjuvant chemotherapy (NAC) has enabled the prediction of treatment response and long-term prognoses; additional adjuvant chemotherapy targeting remaining tumor cells after NAC improves survival. The activation of antitumor immunity by anticancer agents may be involved in the eradication of residual tumor cells. Elucidation of the manner in which antitumor immunity is induced by anticancer agents and unknown factors, and the overcoming of drug resistance via the targeted eradication of residual tumor cells based on genomic profiles, will inevitably lead to the achievement of 0% distant recurrence and a complete cure for primary breast cancer.

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Section: Induction Of Antitumor Immunity After Neoadjuvant and Adjsupporting

confidence: 73%

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

Kim¹,

Kin

2021

Cancers

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“…However, this is based on clinical trial design and it is unclear if this is the optimal frequency for patients. Modification of cardiac surveillance frequency has been proposed by pretreatment risk [ 57 ] and by symptoms during the COVID-19 pandemic, with delay or lengthened intervals for echocardiograms in asymptomatic breast cancer patients in stable condition [ 58 ].…”

Section: Clinical Presentation Part 2: Risk Mitigation Strategies and Mmentioning

confidence: 99%

Heart failure prevention and monitoring strategies in HER2-positive breast cancer: a narrative review

Jafari

Akhter

2021

Breast Cancer Res Treat

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Purpose Cardiotoxicity from anti-human epidermal growth factor receptor 2 (HER2) therapy carries a short-and long-term risk of incident heart failure and increased cardiovascular mortality in patients with breast cancer. Interruptions in anti-HER2 therapy due to cardiotoxicity can lead to suboptimal cancer treatment. The purpose of this narrative review is to outline opportunities to optimize cardiovascular care in patients with HER2-positive breast cancer to prevent interruptions in therapy. Methods This case-based review presents the current literature on evidence-based strategies for personalized cardiotoxicity risk assessment, risk mitigation interventions, cardiac function surveillance tools, and management of asymptomatic left ventricular dysfunction in breast cancer patients receiving anti-HER2 therapy. Results Pretreatment cardiac risk assessment incorporates both treatment-related risk factors and patient-related risk factors for the development of cardiac dysfunction. Prevention and monitoring strategies while on treatment utilize risk factor modification, imaging and biomarker surveillance. Management of asymptomatic left ventricular dysfunction due to anti-HER2 therapy is evolving. Permissive cardiotoxicity in asymptomatic patients while starting cardioprotective therapies requires close collaboration between oncology and cardiology, and referral to cardio-oncology if available. Conclusions Patient-centered, multimodal strategies to prevent, detect, and manage cardiotoxicity from anti-HER2 therapy are necessary to improve outcomes in patients with HER2-positive breast cancer.

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“…Surprisingly, the recently presented IMpassion131 study, which combined atezolizumab with conventional paclitaxel in advanced TNBC, did not improve PFS or OS vs. placebo + paclitaxel [41] . Potential reasons for this obvious contrast with the benefit seen in IMpassion130 still need further exploration, although several hypotheses (e.g., differences within the study population as well as different taxanes and the role of steroids) are under discussion [42] .…”

Section: Icpi In Advanced Breast Cancermentioning

confidence: 99%

Immuno-oncology in triple-negative breast cancer

Heimes¹,

Schmidt²

2021

JCMT

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The immune system plays an important role in breast cancer. Triple-negative breast cancer (TNBC) has a higher mutational load compared to other subtypes. In addition, higher levels of tumor-associated antigens suggests that immunotherapies are a promising treatment option especially for TNBC. Our review discusses both the complexity of the immune system and the cancer immune-cell cycle. In fact, a higher level of tumor-infiltrating lymphocytes is associated with an improved prognosis as well as a better response to chemotherapy in TNBC. Important target structures within the cancer immune-cell cycle are the so-called "immune checkpoints". Immune checkpoint inhibitors (ICPi) block the interaction of certain cell surface proteins that serve as "brakes" of immune reactions. Recent studies have shown ICPi improved survival in early as well as advanced TNBC. However, this has the price of increasing, mainly, immune-mediated toxicity. ICPi strengthen tumor-specific T cell-mediated immunity by "releasing the brake" of the immune system. In combination with chemotherapy, ICPi are already approved for TNBC. As a further step, individualized vaccination strategies against tumor-associated neoantigens represent another promising approach. A liposome-formulated intravenous RNA vaccine encoding different tumorassociated antigens is currently being studied in TNBC and leads to neoantigen-specific immune responses. These novel strategies will improve the prognosis of patients with triple-negative breast cancer.

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Atezolizumab in metastatic triple-negative breast cancer: IMpassion130 and 131 trials - how to explain different results?

Cited by 39 publications

References 12 publications

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

Heart failure prevention and monitoring strategies in HER2-positive breast cancer: a narrative review

Immuno-oncology in triple-negative breast cancer

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