Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting

Prete, Salvatore Del; Montella, Liliana; Arpino, Grazia; Buono, Giuseppe; Buonerba, Carlo; Dolce, Pasquale; Fiorentino, Olga; Aliberti, Maria; Febbraro, Antonio; Savastano, Clementina; Colantuoni, Giuseppe; Riccardi, Ferdinando; Ruggiero, Angelo; Placido, Sabino De; Orditura, Michele

doi:10.18632/oncotarget.27603

Cited by 9 publications

(10 citation statements)

References 32 publications

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“…The proportion of our cohort with previous (neo)adjuvant treatment with trastuzumab (48%) was also similar to that reported in other observational studies [ [19] , [20] , [21] ]. The high proportion of patients treated with first-line T-DM1 who received (neo)adjuvant trastuzumab in our cohort (81%) likely reflects Australian prescribing restrictions for T-DM1 that require patients to relapse on or within 6 months of completing adjuvant trastuzumab in order to access first-line T-DM1, and overall, T-DM1 appears to have been used largely within Australian prescribing restrictions [ 22 ].…”

Section: Discussionsupporting

confidence: 89%

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

et al. 2021

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We aim to describe the treatment patterns and overall survival (OS) outcomes in patients receiving trastuzumab emtansine (T-DM1) for HER2-positive metastatic breast cancer (HER2þMBC) in routine clinical care. Methods: Retrospective, whole-of-population cohort study of people initiating T-DM1 for HER2þMBC between October 2015 and May 2019 in Australia. We used dispensing claims to estimate time-to-T-DM1 initiation, duration of treatment, and treatments administered prior to and following T-DM1 therapy. We estimated OS from T-DM1 initiation and stratified results based on whether patients received firstor second-line T-DM1 treatment. We benchmarked outcomes to those reported in the pivotal, EMILIA trial. Results: 345 patients initiated T-DM1: 309 as second-line therapy for HER2þMBC and 36 as first-line therapy. 51% of patients had received endocrine therapy and 98% of second-line patients received pertuzumab prior to starting T-DM1. The median age was 57 years (53 in EMILIA); median time-to-T-DM1initiation from start of HER2-targeted therapy for HER2þMBC was 11.6 months (IQR: 7.9e16.6); median duration of T-DM1 treatment was 6.5 months (3.1e13.5; 7.6 months in EMILIA), and median OS was 19.3 months (7.9e29.5; 29.9 months in EMILIA). Conclusions: Our findings highlight differences in patient characteristics (older, more previous pertuzumab therapy) and outcomes (shorter OS) from the T-DM1 pivotal trial and provide real-world estimates that can inform patient, clinician and policy, decisions around the use of HER2-targeted therapies in routine clinical care.

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Section: Discussionsupporting

confidence: 89%

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

et al. 2021

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“…On the contrary, T-DM1 clearly demonstrated its superiority over the therapeutic standard in terms of both PFS and OS in second and further lines in two phase III RCTs 13 , 14 and several ‘real-world’ observational studies, also in patients pretreated with P + T + taxanes. 21 , 23 , 40 , 41 , 42 Therefore, apart from prescribing caveats, the currently available evidence is clear in highlighting a major efficacy of the pertuzumab-based regimens in first-line and of T-DM1 in second and further lines. In this perspective, our study shed a light on the specific subset of early-relapsing patients and suggests a potential superiority of P + T + taxane over T-DM1 as first-line treatment of this prognostically unfavored subgroup.…”

Section: Discussionmentioning

confidence: 99%

T-DM1 versus pertuzumab, trastuzumab and a taxane as first-line therapy of early-relapsed HER2-positive metastatic breast cancer: an Italian multicenter observational study

Schettini

Conte

Buono³

et al. 2021

ESMO Open

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Background The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (+) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P + T + taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include early-relapsing patients, defined as patients experiencing tumor relapse ≤12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing ≤6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting. Patients and methods We retrospectively compared T-DM1 versus P + T + taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian ‘real-world’ setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients' characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were two-sided and a P ≤ 0.05 was considered statistically significant. Results Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P + T + taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P + T + taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P = 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P = 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (≤6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival ( P = 0.095). Conclusions Our study suggests superiority for P + T + taxane over T-DM1 as up-front treatment of early-relapsing HER2+ metastatic breast cancer, which merits further assessment in larger and prospective trials.

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“…At that time, these results firmly established T‐DM1 as the standard second‐line treatment for patients with metastatic, HER2‐positive BC 24 . It is essential to note that standard first‐line therapy has changed since—now consisting of dual HER2 blockade with trastuzumab and pertuzumab plus a taxane (THP); however, recent analysis suggests meaningful activity of T‐DM1, even after progression on first‐line THP treatment 25 …”

Section: Current Clinical Indications Of Approved Adcs For Solid Tumorsmentioning

confidence: 91%

Antibody–drug conjugates: Smart chemotherapy delivery across tumor histologies

Tarantino

Pestana

Corti

et al. 2021

CA A Cancer J Clinicians

219

115

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As distinct cancer biomarkers have been discovered in recent years, a need to reclassify tumors by more than their histology has been proposed, and therapies are now tailored to treat cancers based on specific molecular aberrations and immunologic markers. In fact, multiple histology‐agnostic therapies are currently adopted in clinical practice for treating patients regardless of their tumor site of origin. In parallel with this new model for drug development, in the past few years, several novel antibody–drug conjugates (ADCs) have been approved to treat solid tumors, benefiting from engineering improvements in the conjugation process and the introduction of novel linkers and payloads. With the recognition that numerous surface targets are expressed across various cancer histologies, alongside the remarkable activity of modern ADCs, this drug class has been increasingly evaluated as suitable for a histology‐agnostic expansion of indication. For illustration, the anti‐HER2 ADC trastuzumab deruxtecan has demonstrated compelling activity in HER2‐overexpressing breast, gastric, colorectal, and lung cancer. Examples of additional novel and potentially histology‐agnostic ADC targets include trophoblast cell‐surface antigen 2 (Trop‐2) and nectin‐4, among others. In the current review article, the authors summarize the current approvals of ADCs by the US Food and Drug Administration focusing on solid tumors and discuss the challenges and opportunities posed by the multihistological expansion of ADCs.

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Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting

Cited by 9 publications

References 32 publications

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

T-DM1 versus pertuzumab, trastuzumab and a taxane as first-line therapy of early-relapsed HER2-positive metastatic breast cancer: an Italian multicenter observational study

Antibody–drug conjugates: Smart chemotherapy delivery across tumor histologies

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