Abstract GS1-02: Phase 3 SOPHIA study of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: second interim overall survival analysis

Rugo, Hope S.; Im, Seock‐Ah; Cardoso, Fátima; Cortés, Javier; Curigliano, Giuseppe; Pegram, Mark D.; Musolino, Antonino; Bachelot, Thomas; Wright, Gail S.; Laurentiis, Michelino De; Kaufman, Peter A.; Pluard, Timothy; Ricci, Francesco; Salazar, Lupe G.; Yardley, Denise A.; Edlich, Sutton; Hong, Shengyan; Rock, Edwin P.; Gradishar, William J.

doi:10.1158/1538-7445.sabcs19-gs1-02

Cited by 39 publications

(36 citation statements)

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“…A similar but not significant trend was observed in term of OS (HR, 0.79; 95% CI, 0.61–1.04; p = 0.087). More infusion-related reactions were observed with margetuximab [ 31 , 32 ], but overall safety was favorable and considered as similar to trastuzumab.…”

Section: Novel Anti-her2 Antibodiesmentioning

confidence: 99%

New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?

Mezni

Vicier

Guérin

et al. 2020

Cancers

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Over the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine. The management of this breast cancer subgroup has thus been revolutionized and its prognosis has changed dramatically. Nevertheless, HER2-positive advanced breast cancer remains an incurable disease and resistance to conventional anti-HER2 drugs is almost unavoidable. Nowadays, biochemical and pharmaceutical advances are meeting the challenge of developing increasingly sophisticated therapies directed against HER2, including novel anti HER2 antibodies with increased affinity. New antibody-drug conjugates (ADC) with more advanced pharmacological properties, and dual targeting of epitopes via bispecific monoclonal antibodies are also emerging. In addition, more potent and more specific HER2 tyrosine kinase inhibitors have shown interesting outcomes and are under development. Finally, researchers’ interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.

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Section: Novel Anti-her2 Antibodiesmentioning

confidence: 99%

New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?

Mezni

Vicier

Guérin

et al. 2020

Cancers

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“…In addition, adaptive immunity is to be induced. In the phase III "SOPHIA" study with 536 intensively pretreated patients, the combination with margetuximab plus chemotherapy was noted to be slightly superior to the administration of trastuzumab and chemotherapy [14]. The progression-free survival was extended from 4.9 to 5.8 months (HR 0.76, p < 0.033).…”

Section: Margetuximabmentioning

confidence: 99%

Update Breast Cancer 2020 Part 2 – Advanced Breast Cancer: New Treatments and Implementation of Therapies with Companion Diagnostics

Lüftner

Schneeweiß

Hartkopf

et al. 2020

Geburtshilfe Frauenheilkd

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For patients with locally advanced or metastatic breast cancer, new and effective therapies such as CDK4/6 inhibitors, PARP inhibitors and a PD-L1 inhibitor have been introduced in recent years. This review presents an update on the available studies with their data. In addition, two innovative anti-HER2 therapies are presented (trastuzumab-deruxtecan and tucatinib) for which the results from new studies have been reported. Molecular tests offer the possibility of defining patient populations or also monitoring courses of therapy. This can help identify patients with specific characteristics in order to provide them with individually targeted therapy within the framework of studies. In a large study, the benefit of such a biomarker study was able to be described for the first time.

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“…AEs caused the death of 3 patients in the margetuximab arm and 2 in the trastuzumab arm. However, none of these events was considered antibody-related [32].…”

Section: Margetuximabmentioning

confidence: 99%

Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives

Dormann¹

2020

Breast Care

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Background: The basis of improved systemic therapy for inoperable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer is formed by HER2-targeting monoclonal antibodies. Dual HER2 blockade with pertuzumab and trastuzumab in combination with docetaxel in previously untreated patients, and trastuzumab emtansine (T-DM1, an antibody-drug conjugate [ADC] consisting of trastuzumab, a linker and a cytotoxic payload) after prior trastuzumab therapy have demonstrated progression-free survival (PFS) and overall survival (OS) superior to what was achieved with the previous treatment routine. Therefore, pertuzumab and trastuzumab with chemotherapy (preferably with a taxane) and T-DM1 are considered the current standard of care in the first- and second-line settings, respectively. For later lines of therapy, no uniformly recognized standard of care has been defined. Accepted options include treatment with trastuzumab beyond progression, in combination with a broad variety of single-agent chemotherapies used sequentially, or lapatinib (an HER2-targeting tyrosine kinase inhibitor [TKI]) in combination with either trastuzumab or capecitabine. However, most of these options have not been formally tested in patients receiving the current standard of care therapy for metastatic disease. Summary: In patients previously treated with today’s standard of care, including a significant subgroup with untreated or progressing brain metastases, the combination of tucatinib, a novel HER2-targeting TKI, with trastuzumab and capecitabine, demonstrates a clinically meaningful improvement in PFS and OS when compared to placebo with trastuzumab and capecitabine. Neratinib, another HER2 TKI, in combination with capecitabine, compared to lapatinib and capecitabine, as well as margetuximab, an HER2-directed monoclonal antibody with a fragment c (Fc) domain engineered to enhance immune activation, compared to trastuzumab, both combined with the investigator’s choice of chemotherapy, showed a statistically significantly longer PFS. However, not all patients in the respective trials had received pertuzumab and T-DM1 prior to enrollment and, so far, no improvement in OS has been demonstrated. After a median of 6 prior lines of therapy, trastuzumab deruxtecan (T-DXd), a novel ADC, showed a meaningful overall response and PFS. Although the safety profile was generally manageable, treatment-related interstitial lung disease (ILD) might pose a challenge in routine practice. Pyrotinib, another HER2 TKI, was evaluated in combination with capecitabine in patients after prior exposure to trastuzumab when pertuzumab and T-DM1 were not available. In this setting, PFS was better than with lapatinib and capecitabine. Key Messages: In 2020, pertuzumab and trastuzumab with taxane-based chemotherapy in the first line, and T-DM1 in the second line, remain the standard of care. Tucatinib, neratinib, margetuximab, and T-DXd expand the armamentarium for treatment beyond the second line. Pyrotinib might be another option, especially for patients, who do not have access to pertuzumab and T-DM1.

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Abstract GS1-02: Phase 3 SOPHIA study of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: second interim overall survival analysis

Cited by 39 publications

References 0 publications

New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?

New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?

Update Breast Cancer 2020 Part 2 – Advanced Breast Cancer: New Treatments and Implementation of Therapies with Companion Diagnostics

Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives

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