VP6-2021: IMpassion050: A phase III study of neoadjuvant atezolizumab + pertuzumab + trastuzumab + chemotherapy (neoadj A + PH + CT) in high-risk, HER2-positive early breast cancer (EBC)

Huober, Jens; Barrios, Carlos H.; Niikura, Naoki; Jarząb, Michał; Chang, Yun‐Chen; Huggins-Puhalla, Shannon Leigh; Graupner, Vilma; Eiger, Daniel; Henschel, Volkmar; Gochitashvili, N; Lambertini, Chiara; Restuccia, Eleonora; Zhang, H.

doi:10.1016/j.annonc.2021.05.800

Cited by 31 publications

(26 citation statements)

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“…•High incidence of adverse events •Not all patients express PDL1 •No increasing pCR in combination with chemotherapy drugs (10)(11)(12)(13)(14)(15) PDL1: atezolizumab, durvalumab…”

Section: Fdaapprovedmentioning

confidence: 99%

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Targeted Therapeutic Strategies for Triple-Negative Breast Cancer

Zhan

Yin

et al. 2021

Front. Oncol.

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Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression and the absence of human epidermal growth factor receptor 2 (HER2) expression/amplification. Conventional chemotherapy is the mainstay of systemic treatment for TNBC. However, lack of molecular targeted therapies and poor prognosis of TNBC patients have prompted a great effort to discover effective targets for improving the clinical outcomes. For now, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi’s) and immune checkpoint inhibitors have been approved for the treatment of TNBC. Moreover, agents that target signal transduction, angiogenesis, epigenetic modifications, and cell cycle are under active preclinical or clinical investigations. In this review, we highlight the current major developments in targeted therapies of TNBC, with some descriptions about their (dis)advantages and future perspectives.

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“…•High incidence of adverse events •Not all patients express PDL1 •No increasing pCR in combination with chemotherapy drugs (10)(11)(12)(13)(14)(15) PDL1: atezolizumab, durvalumab…”

Section: Fdaapprovedmentioning

confidence: 99%

“…In the neoadjuvant phase, patients with Grade 3/4 or more serious AEs were increased in the atezolizumab group. There were 4 patients with Grade 5 AEs, including alveolitis, septic shock, sepsis, and COVID-19, in the neoadjuvant phase and 1 patient in the adjuvant phase (11).…”

Section: Immune Checkpoint Inhibitors and Clinical Trials In Tnbcmentioning

confidence: 99%

Targeted Therapeutic Strategies for Triple-Negative Breast Cancer

Zhan

Yin

et al. 2021

Front. Oncol.

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“…133 The recently released data from the primary analysis of the IMpassion050 study showed no benefit from adding atezolizumab to preoperative atezolizumab plus pertuzumab, trastuzumab, and chemotherapy in terms of pCR both in the overall population and PD-L1-positive tumors (62.4% in the atezolizumab arm versus 62.7% in the placebo arm). 126 Given the high heterogeneity of TNBC, it is opportune to conceive biology-driven clinical trials wherein patients may be treated based on their specific tumor molecular profile.…”

Section: Her2-positive Early Breast Cancermentioning

confidence: 99%

“…In addition, low RAD51 scores, high tumor-infiltrating lymphocytes (TILs), and high programmed death–ligand 1 (PD-L1) expression levels correlate to the olaparib response. 126 An exploratory study of the RIO trial (EudraCT 2014-003319-12) in treatment-naïve patients with early-stage TNBC who received the PARP inhibitor rucaparib showed that 75% of tumors with known homologous recombination repair alterations had low RAD51 foci at baseline. Of the HRD-positive tumors, 70% had low RAD51 foci, while none of the HRD-negative tumors had low RAD51 foci.…”

Section: (Neo)adjuvant Model As a Platform For Research And Innovativ...mentioning

confidence: 99%

Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects

et al. 2021

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Drug approval for early-stage breast cancer (EBC) has been historically granted in the context of registration trials based on adequate outcomes such as disease-free survival and overall survival. Improvements in long-term outcomes have made it more difficult to demonstrate the clinical benefit of a new cancer drug in large, randomized, comparative clinical trials. Therefore, the use of surrogate endpoints rather than traditional measures allows for cancer drug trials to proceed with smaller sample sizes and shorter follow-up periods, which reduces drug development time. Among surrogate endpoints for breast cancer, the increase in pathological complete response (pCR) rates was considered appropriate for accelerated drug approval. The association between pCR and long-term outcomes was strongest in patients with aggressive tumor subtypes, such as triple-negative and human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor-negative breast cancers. Whereas in hormone receptor-positive/HER2-negative EBC, the most accepted surrogate markers for endocrine therapy–based trials include changes in Ki67 and the preoperative endocrine prognostic index. Beyond the classic endpoints, further prognostic tools are required to provide EBC patients with individualized and effective therapies, and the neoadjuvant setting provides an excellent platform for drug development and biomarker discovery. Nowadays, the availability of multigene signatures is offering a standardized quantitative and reproducible tool to potentiate the efficacy of standard treatment for high-risk patients and develop de-escalated treatments for patients at lower risk of relapse. In this article, we first evaluate the surrogacies used for long-term outcomes and the underlying evidence supporting the use of each surrogate endpoint for the accelerated or regular drug approval process in EBC. Next, we provide an overview of the most recent studies and innovative strategies in a (neo)adjuvant setting as a platform to accelerate new drug approval. Finally, we highlight some clinical trials aimed at tailoring systemic treatment of EBC using prognosis-related factors or early biomarkers of drug sensitivity or resistance.

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“… 31 Conversely the IMpassion050, a Phase 3 study that assessed HER2 targeted therapy, chemotherapy with or without atezolizumab in the neoadjuvant setting, showed no increase of pathologic complete response with the addition of atezolizumab, regardless of the PD-L1 status. 32 There are currently no ICIs approved for the treatment of HER2+ breast cancer, although there are ongoing studies assessing the role of ICIs in selected HER2+ and PD-L1+ tumors. The combination of margetuximab with ICIs represents an attractive option to enhance immunity of tumors traditionally considered immunologically quiescent especially since safety data are available for this combination in gastrointestinal malignancies.…”

Section: Introductionmentioning

confidence: 99%

Profile of Margetuximab: Evidence to Date in the Targeted Treatment of Metastatic HER2-positive Breast Cancer

Schlam¹,

Nunes²,

Lynce³

2022

OTT

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VP6-2021: IMpassion050: A phase III study of neoadjuvant atezolizumab + pertuzumab + trastuzumab + chemotherapy (neoadj A + PH + CT) in high-risk, HER2-positive early breast cancer (EBC)

Abstract: This abstract is presented as part of the ESMO Virtual Plenaries programme (https://www.esmo.org/meetings/esmovirtual-plenaries) and eligible for encore presentation at the ESMO 2021 Congress.

Cited by 31 publications

References 0 publications

Targeted Therapeutic Strategies for Triple-Negative Breast Cancer

Targeted Therapeutic Strategies for Triple-Negative Breast Cancer

Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects

Profile of Margetuximab: Evidence to Date in the Targeted Treatment of Metastatic HER2-positive Breast Cancer

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