Publications by authors named "G Curigliano"

464 Publications

The role of tyrosine kinase inhibitors in the treatment of HER2+ metastatic breast cancer.

Eur J Cancer 2021 Jul 16;154:175-189. Epub 2021 Jul 16.

Department of Oncology and Hemato-Oncology, University of Milano and European Institute of Oncology, IRCCS, Milano, Italy.

The introduction of trastuzumab and other subsequent human epidermal growth factor receptor 2 (HER2)-targeted therapies dramatically shifted the treatment landscape of HER2+ breast cancer, changing the natural history of the disease. There is no standard-of-care for patients with HER2+ metastatic breast cancer (MBC) in third and later lines of treatment; however, continued use of anti-HER2 therapies is recommended. Small-molecule tyrosine kinase inhibitors (TKIs) that target HER2 and other HER family receptors play a central role in this setting. TKIs have demonstrated various degrees of efficacy against central nervous system (CNS) metastases, which are a major clinical challenge for patients with HER2+ MBC. The TKIs lapatinib, neratinib, and tucatinib have received regulatory approval for the treatment of HER2+ MBC, while pyrotinib and afatinib have been evaluated in this setting. These TKIs vary by molecular weight, HER protein specificity and reversibility of binding and in turn have unique safety profiles. Toxicities reported in clinical trials of TKIs in HER2+ MBC that may require specific management strategies include diarrhoea, palmar-plantar erythrodysesthesia syndrome and rash. Here, we review the efficacy data, including CNS activity, and the safety profiles of the TKIs, and we provide guidance on adverse event management. Finally, we discuss how to incorporate the TKIs into the HER2+ MBC treatment algorithm.
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http://dx.doi.org/10.1016/j.ejca.2021.06.026DOI Listing
July 2021

CUSTOMIZING LOCAL AND SYSTEMIC THERAPIES FOR WOMEN WITH EARLY BREAST CANCER: The St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.

Ann Oncol 2021 Jul 6. Epub 2021 Jul 6.

Medical University of Vienna (Austria).

The 17 St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID19 pandemic. More than 3,300 participants took part in this important bi-annual critical review of the "state of the art" in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix) from all continents discussed and commented on the previously elaborated consensus questions as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's Conference was "Customizing local and systemic therapies." A well-organized program of pre-recorded symposia, live panel discussions, and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response prior to surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical, and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.
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http://dx.doi.org/10.1016/j.annonc.2021.06.023DOI Listing
July 2021

Preservation of quality of life in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial).

Eur J Cancer 2021 Aug 29;153:223-233. Epub 2021 Jun 29.

Biometrics, Seagen Inc., Bothell, WA, USA.

Aims: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB.

Methods: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3-9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit.

Results: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed ≥1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (≥7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm.

Conclusions: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases.

Clinical Trial Registration: NCT02614794.
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http://dx.doi.org/10.1016/j.ejca.2021.05.025DOI Listing
August 2021

Antibody-Drug Conjugates for the Treatment of Breast Cancer.

Cancers (Basel) 2021 Jun 9;13(12). Epub 2021 Jun 9.

Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy.

Metastatic breast cancer (BC) is currently an incurable disease. Besides endocrine therapy and targeted agents, chemotherapy is often used in the treatment of this disease. However, lack of tumor specificity and toxicity associated with dose exposure limit the manageability of cytotoxic agents. Antibody-drug conjugates (ADCs) are a relatively new class of anticancer drugs. By merging the selectivity of monoclonal antibodies with the cytotoxic properties of chemotherapy, they improve the therapeutic index of antineoplastic agents. Three core components characterize ADCs: the antibody, directed to a target antigen; the payload, typically a cytotoxic agent; a linker, connecting the antibody to the payload. The most studied target antigen is HER2 with some agents, such as trastuzumab deruxtecan, showing activity not only in HER2-positive, but also in HER2-low BC patients, possibly due to a bystander effect. This property to provide a cytotoxic impact also against off-target cancer cells may overcome the intratumoral heterogeneity of some target antigens. Other cancer-associated antigens represent a strategy for the development of ADCs against triple-negative BC, as shown by the recent approval of sacituzumab govitecan. In this review, we discuss the current landscape of ADC development for the treatment of BC, as well as the possible limitations of this treatment.
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http://dx.doi.org/10.3390/cancers13122898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229763PMC
June 2021

First line treatment of BRAF mutated advanced melanoma: Does one size fit all?

Cancer Treat Rev 2021 Jun 18;99:102253. Epub 2021 Jun 18.

Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy.

In the last decade, immunotherapy and target therapy have revolutionized the prognosis of patients with BRAF-V600 mutation-positive metastatic melanoma. To date, three different combinations of BRAF/MEK inhibitors have been approved for this population, showing comparable efficacy and unique toxicity profiles. Several immune-checkpoint inhibitors, including pembrolizumab, nivolumab and the combination of nivolumab plus ipilimumab, are also available options for untreated metastatic melanoma patients. A novel approach has emerged by combining immune-checkpoint inhibitors and targeted agents, based on preclinical hints of synergy, prompting clinical results from large randomized trials. Specifically, the triplet of atezolizumab, vemurafenib and cobimetinib has been recently approved by FDA for patients with untreated BRAF-mutant metastatic melanoma. With a wide variety of available treatment options in this setting, it is paramount to establish criteria to select the most effective and safe frontline tailored approaches, for each patient. Results from ongoing studies are awaited, to maximise the benefits in survival outcomes and quality of life for patients, balancing adverse events and clinical benefit. The purpose of this review is to summarize the current landscape of standard and experimental treatment strategies for the first line treatment of patients with BRAF-mutated advanced melanoma and discuss the best patient-centered tailored strategies in the first-line setting.
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http://dx.doi.org/10.1016/j.ctrv.2021.102253DOI Listing
June 2021
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