Trastuzumab duocarmazine is an antibody drug conjugate that targets the HER2 protein with trastuzumab to deliver the cytotoxin duocarmycin after internalisation. Presented by Dr Cristina Saura (Vall d’Hebron Institute of Oncology, Spain), the TULIP trial (NCT03262935) aimed to demonstrate that trastuzumab duocarmazine (1.2 mg/kg every 3 weeks) is superior to physician's choice of treatment in prolonging PFS per blinded independent central review, as its primary endpoint [1].
Eligible patients were randomly assigned 2:1 to receive trastuzumab duocarmazine (n=291) or physician's choice treatment (n=146) until disease progression or unacceptable toxicity. Physician’s choice of treatment included lapatinib plus capecitabine, trastuzumab plus capecitabine, trastuzumab plus vinorelbine, or trastuzumab plus eribulin. This randomised, active-controlled, superiority study in patients with unresectable locally advanced or metastatic HER2-positive breast cancer enrolled patients who had either progression during or after at least 2 HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after trastuzumab emtansine (T-DM1) treatment. Key secondary endpoints were overall survival (OS), investigator-assessed PFS, objective response rate, and patient-reported outcomes for health-related quality of life.
The primary endpoint of centrally reviewed improved PFS was met, with a median of 7.0 months (95% CI 5.4–7.2 months) for patients in the trastuzumab duocarmazine arm compared with 4.9 months (95% CI 4.0–5.5 months) for physician’s choice chemotherapy (P=0.002). Likewise, the secondary endpoint of investigator-assessed PFS was also met; patients in the trastuzumab duocarmazine arm had a median PFS of 6.9 months (95% CI 6.0–7.2 months) versus 4.6 months (95% CI 4.0–5.6 months) in the physician’s choice arm.
At the timepoint of this interim analysis, OS was not statistically significant: 20.4 months in the group taking trastuzumab duocarmazine versus 16.3 months in the group following their physician’s choice of therapy (HR 0.83; 95% CI 0.62–1.09; P=0.153). The other key secondary endpoints, objective response rate and health-related quality of life, also showed no statistically significant differences between the 2 arms. Final analyses of these endpoints will be evaluated after the data have matured with follow-up.
Safety signals were manageable, and no cardiotoxicity was observed. The most frequent adverse events for trastuzumab duocarmazine were conjunctivitis (38.2%), keratitis (38.2%), and fatigue (33.3%). Interstitial lung disease/pneumonitis occurred in 7.6% of patients on the drug, including 5.2% grade 1-2 events, and 2 grade 5 events.
- Saura Manich C, et al. Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER-positive locally advanced or metastatic breast cancer. Abstract LBA15, ESMO Congress 2021, 16–21 September.
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Table of Contents: ESMO 2021
Featured articles
Breast Cancer
Trastuzumab deruxtecan triples PFS
Novel conjugate meets primary endpoint
Longest survival benefit from first-line CDK4/6 inhibitor
Meta-analysis shows 6-months adjuvant trastuzumab is optimal
Double-positive results for triple-negative metastatic breast cancer
Survival after neoadjuvant therapy with trastuzumab-lapatinib plus chemotherapy
Postmenopausal breast cancer: extended letrozole reduces recurrence
Asian women also benefit from palbociclib plus letrozole
No PEARLs of survival with palbociclib plus endocrine therapy compared with capecitabine, but QoL better
Gastrointestinal Cancer
Neoadjuvant chemotherapy potential alternative to neoadjuvant chemoradiotherapy in LARC
Immune chemo-sensitisation looks promising in microsatellite-stable mCRC
Adagrasib shows promising clinical activity in heavily pretreated KRAS-mutated CRC
Automated detection of microsatellite status on unstained samples in early colon cancer
Consistent benefit of anti-PD-1 therapy for oesophageal and gastric cancer
HIPEC in gastric cancer with peritoneal metastases
ctDNA highly predictive in HER2-positive, advanced gastric or gastro-oesophageal junction cancer
Lung Cancer
Robust anticancer activity of trastuzumab deruxtecan in HER2-mutated NSCLC
Nivolumab/ipilimumab continues to provide survival benefit in unresectable MPM
Adjuvant atezolizumab lowers relapse rate in resected NSCLC
Three-year OS follow-up from CASPIAN trial
TCR clonality predicts pembrolizumab response in NSCLC
Melanoma
Adjuvant immunotherapy reduces risk of disease recurrence in stage II melanoma
IFN-γ signature predicts response to immunotherapy
Updated results of SECOMBIT trial
Combining T-VEC and pembrolizumab does not significantly improve survival in advanced, unresectable melanoma
Durable intracranial responses with nivolumab/ipilimumab
Genitourinary Cancer
TKI drug-free interval strategy not detrimental to conventional continuation strategy in RCC
Modified ipilimumab schedule reduces risk of grade 3/4 adverse events
Optimal neoadjuvant dose ipilimumab/nivolumab in stage III urothelial cancer
Better survival with neoadjuvant dose-dense MVAC regimen in MIBC
PARP inhibitor rechallenge improves PFS in ovarian cancer
Pembrolizumab prolongs survival in persistent, recurrent, or metastatic cervical cancer
Pembrolizumab has durable effect in previously treated MSI-H/dMMR advanced endometrial cancer
HRR mutational status is prognostic and predictive biomarker olaparib activity
Haematological Cancer
Mutational analyses are predictive in malignant lymphomas
Low numbers of M2 macrophages in tumour microenvironment associated with superior response to immunotherapy in Hodgkin lymphoma
COVID-19
Adequate response to SARS-CoV-2 vaccine in cancer patients
Cancer patients more likely to die from COVID-19 when hospital admittance is required
Third global survey of the ESMO Resilience Task Force
High COVID-19 mortality in Swiss cancer patients
Basic Science & Translational Research
Neutrophils negatively correlate with response to anti-PD-1 monotherapy in dMMR tumours
Tetraspecific ANKETs harnesses innate immunity in cancer therapies
Early ctDNA reduction in metastatic uveal melanoma correlates better with OS than RECIST response
Gut microbiota as a potential predictive biomarker
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