Featured video: A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01.
In an initial report of patients with heavily pre-treated metastatic, HER2-expressing colorectal cancer (mCRC), preliminary efficacy was observed with trastuzumab deruxtecan, particularly in patients with the highest degree of HER2 positivity.
Prof. Salvatore Siena (University of Milan Niguarda Cancer Center, Italy) presented results from the DESTINY-CRC01 study, which stratified 3 cohorts of patients [1]. Cohort A had HER2-overexpressing patients who had scores of 3 or higher according to immunohistochemistry testing (IHC 3 plus), as well as a score above 2 by in situ hybridisation (ISH). Cohort B were patients whose tumours were IHC 2 and above but were ISH-negative; cohort C were patients whose tumours were IHC >1. All patients (n=90) enrolled in the trial had tumours that were RAS/BRAF wildtype and expressed HER2. A single patient had an NRAS mutation. All had received at least 2 prior lines of therapy, including other HER2-targeting agents such as trastuzumab. Patients had a median of 4 prior therapies.
The primary endpoint of this study was overall response rate (ORR), which was 45.3%. A single patient had a complete response to the treatment and 23 patients had partial responses. Additionally, 20 patients achieved stable disease, resulting in an overall 83% control rate. In cohorts B and C, there were no confirmed responses. The median progression-free survival for patients in cohort A was 6.9 months, although neither the median duration of response nor the median overall survival was reached.
Prof. Siena noted that the absence of any responses in the 2 cohorts with low HER2 expression (B and C) suggests that the promising durable activity seen with trastuzumab deruxtecan is likely restricted to those with high levels of HER2 expression.
Testing patients to guide precision treatment strategies is becoming standard practice in mCRC, including mutation screening for KRAS/RAS and BRAF, HER2 amplifications, mismatch repair deficiency/microsatellite instability, and NTRK fusions. Although preliminary, these data may indicate the importance of testing for HER2 expression as well.
- Siena S, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 4000.
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Table of Contents: ASCO 2020
Featured articles
COVID-19 & Telemedicine
COVID-19 and Cancer Consortium Registry: initial results
Oncology hospital-at-home model reduces hospitalizations, emergency department visits, and costs
Nurse-led telephone triage system reduces hospitalizations, helps patients manage symptoms at home
Melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Pembrolizumab plus low-dose ipilimumab well tolerated after progression on PD1 antibody therapy
Toripalimab plus axitinib effective in metastatic mucosal melanoma
Breast & Ovarian Cancer
Advanced breast cancer: locoregional therapy does not improve OS
T-DM1 does not improve safety or efficacy in HER-2 positive early breast cancer; favorable iDFS reported
Maintenance olaparib improves OS in relapsed ovarian cancer with BRCA1/2 mutation
Combination pembrolizumab/chemo improves PFS in metastatic TNBC
Effect of veliparib with or without cisplatin in breast cancer: results of SWOG S1416
PHOEBE, a phase 3 trial comparing pyrotinib and lapatinib in HER2-positive metastatic breast cancer
BYLieve demonstrates efficacy of PIK3CA-directed treatment post CDK4/6-ihibition
Strategies emerge for chemotherapy de-escalation in HER2-positive breast cancer
Multiple Myeloma
Carfilzomib: no PFS benefit for multiple myeloma
Lung Cancer
ES-SCLC: tremelimumab + durvalumab + chemotherapy misses endpoint
Adjuvant osimertinib in NSCLC: practice changing ADAURA trial
ES-SCLC: pembrolizumab KEYNOTE-604 data
Second-line gemcitabine plus ramucirumab significantly improves overall survival
Tiragolumab and atezolizumab: ORR in NSCLC
MET-amplified advanced NSCLC responds well to MET inhibitor capmatinib
Genitourinary Cancer
Urothelial cancer: avelumab works as maintenance therapy
ARAMIS final OS and nmCRPC safety outcomes
Final survival results from phase 3 SPARTAN trial
Novel drug for kidney cancers/VHL patients
Primary analysis from IMvigor010, adjuvant atezolizumab in high risk muscle-invasive urothelial carcinoma
First randomised trial of Lu-PSMA in mCRPC progressing after docetaxel
Gastrointestinal Cancer
HER2-expressing metastatic colorectal cancer: trastuzumab deruxtecan
REGOMUNE: a phase 2 study combining regorafenib and avelumab
Cardiotoxicity: consider switching to S-1
Perioperative chemotherapy for resectable pancreatic ductal adenocarcinoma
Real-world data of sequential sorafenib followed by regorafenib in unresectable HCC
Paediatric Cancer
Sustained improvements in quality of life with larotrectinib
Promising first immunotherapy trial in placental trophoblastic tumours
Precision medicine for poor-prognosis paediatric patients
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