Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial

Peréz-García, José Manuel; Gebhart, Geraldine; Ruíz-Borrego, Manuel; Stradella, Agostina; Bermejo, Begoña; Schmid, Peter; Marmé, Frederik; Escrivá-de-Romaní, Santiago; Calvo, Lourdes; Ribelles, Nuria; Martínez, Noelia; Albacar, Cinta; Prat, Aleix; Dalenc, Florence; Kerrou, K.; Colleoni, Marco; Afonso, Noemia; Cosimo, Serena Di; Sampayo-Cordero, Miguel; Malfettone, Andrea; Cortés, Javier; Llombart–Cussac, Antonio; Investigators, Trial

doi:10.1016/s1470-2045(21)00122-4

Cited by 94 publications

(81 citation statements)

References 28 publications

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“…Detecting the need to increase or reduce the dose or duration of treatment could decrease these toxicities and also improve overall survival [ 48 ]. For this reason, several clinical trials use radiological tests during neoadjuvant treatment to predict a pathological complete response (pCR) and personalize treatment duration and dosage based on these findings [ 49 ]. However, ctDNA could be a more sensitive method to evaluate treatment response.…”

Section: Ctdna In Early Breast Cancermentioning

confidence: 99%

Role of ctDNA in Breast Cancer

Sant

Bernat-Peguera

Felip

et al. 2022

Cancers

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Breast cancer is currently classified by immunohistochemistry. However, technological advances in the detection of circulating tumor DNA (ctDNA) have made new options available for diagnosis, classification, biological knowledge, and treatment selection. Breast cancer is a heterogeneous disease and ctDNA can accurately reflect this heterogeneity, allowing us to detect, monitor, and understand the evolution of the disease. Breast cancer patients have higher levels of circulating DNA than healthy subjects, and ctDNA can be used for different objectives at different timepoints of the disease, ranging from screening and early detection to monitoring for resistance mutations in advanced disease. In early breast cancer, ctDNA clearance has been associated with higher rates of complete pathological response after neoadjuvant treatment and with fewer recurrences after radical treatments. In metastatic disease, ctDNA can help select the optimal sequencing of treatments. In the future, thanks to new bioinformatics tools, the use of ctDNA in breast cancer will become more frequent, enhancing our knowledge of the biology of tumors. Moreover, deep learning algorithms may also be able to predict breast cancer evolution or treatment sensitivity. In the coming years, continued research and the improvement of liquid biopsy techniques will be key to the implementation of ctDNA analysis in routine clinical practice.

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Section: Ctdna In Early Breast Cancermentioning

confidence: 99%

Role of ctDNA in Breast Cancer

Sant

Bernat-Peguera

Felip

et al. 2022

Cancers

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“…At surgery, 37.9% (95% CI = 31.6-44.5; p < 0.001) of 18 F-FDG-PET-responders receiving dual HER2 blockade achieved pCR and reduced toxicity and impact on global health status compared with patients receiving chemotherapy. 86 In contrast to the previous de-escalation studies, the PHERGain trial is powered to evaluate invasive DFS and depending on the 3-year invasive DFS results, this 18 F-FDG-PET-based, pathologic responseadapted strategy may provide useful information to identify patients who may not require chemotherapy, thus offering a new therapeutic option enabling an improvement in quality of life for this patient population.…”

Section: Her2-positive Early Breast Cancermentioning

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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“…At 2–6 weeks after completion of the study, surgery was performed and adjuvant treatment was administered according to previous neoadjuvant treatment, pathological response, hormone receptor status and clinical stage at diagnosis; 227 of 285 (80%) of patients in group B (without chemotherapy) had a 18F-FDG-PET response, of whom 86 of 227 (37.9%) had a pathological complete response versus 25.9% of pCR in non-responders ( p = 0.068). In group A with chemotherapy, the global pCR rate was 57.7%; 65.6 in 18F-FDG-PET responders versus 10% in non-responders ( p = 0.013) [ 33 ]. Hence, 18F-FDG-PET response by variation of uptake could select patients who will have greater pCR rates, however, chemotherapy is still needed in combination with antiHER2 therapies.…”

Section: Early Breast Cancermentioning

confidence: 99%

Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments

Morales

Gasol

Sanchez

2021

Cancers

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HER2 positive breast cancer represent about 20% of all breast cancer subtypes and it was considered the subtype with the worst prognosis until the discovery of therapies directed against the HER2 protein. The determination of the status of the HER2 must be very precise and well managed to identify this subtype, and there are very specific and updated guides that allow its characterization to be adjusted. Treatment in local disease has been considerably improved with less aggressive and highly effective approaches and very high cure rates. In metastatic disease, average median survival rates of 5 years have been achieved. New highly active molecules have also been discovered that allow disease control in very complicated situations. This article reviews all these options that can be used for the management of this disease.

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Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial

Cited by 94 publications

References 28 publications

Role of ctDNA in Breast Cancer

Role of ctDNA in Breast Cancer

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

Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments

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