Earlier this week, pivotal Phase II data were presented for AstraZeneca and Daiichi Sankyo's antibody drug conjugate (ADC) trastuzumab deruxtecan in HER2-positive breast cancer at the San Antonio Breast Cancer Symposium (SABCS).
Results from the DESTINY-Breast01 study showed that 60.9% of patients treated with trastuzumab deruxtecan achieved an objective response rate (ORR), meaning their tumours shrank by at least 30%. The trial enrolled 184 patients who had previously received two or more HER2-targeted treatment regimens. Median duration of response was 14.8 months and median progression-free survival was 16.4 months.
This efficacy does come at a cost, with 14% of patients treated with trastuzumab deruxtecan suffering from pulmonary fibrosis, or interstitial lung disease, four of whom died as a result of this complication, which was deemed by investigators to be treatment related.
Analysts at Jefferies cautioned that this could limit future utilisation in earlier lines of therapy, noting that overall adverse events led to a dose interruption in 35.3% of patients and a dose reduction in 23.4%, whilst 15.2% of patients discontinued therapy.
That said, and in the context of DESTINY-Breast01 having enrolled patients treated with a median of six prior therapies, survival data for the ADC were cited at SABCS as being substantially higher than for any other investigational agent evaluated in pre-treated HER2-positive breast cancer patients.
We are snap-polling oncologists (based in the US, France, Germany and the UK) to gauge their assessment of these results and how they may impact future later line treatment of HER2-positive breast cancer…
Q. Do you routinely treat patients with HER2-positive breast cancer?
Q. Positive data has been presented from the pivotal Phase II single-arm DESTINY-Breast01 trial evaluating trastuzumab deruxtecan, a HER2-targeting antibody drug conjugate (ADC), in patients with HER2-positive metastatic breast cancer who have received two or more prior HER2-targeted regimens. Trastuzumab deruxtecan achieved an objective response rate (ORR) of 60.9%.
Patients had received a median of six prior therapies for metastatic disease. Prior therapies included trastuzumab emtansine (100%), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%), hormone therapies (48.9%) and other systemic therapies (99.5%).
Patients achieved a disease control rate (DCR) of 97.3% with a median duration of response (DoR) of 14.8 months and median progression-free survival (PFS) of 16.4 months. The median overall survival (OS) has not yet been reached, with an estimated survival rate of 86% at one year.
Based on these data, how would you rate the efficacy profile demonstrated by trastuzumab deruxtecan in this setting? Where 1 = poor and 5 = excellent
1 2 3 4 5
Q. Regarding safety, the most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (20.7%), anaemia (8.7%), nausea (7.6%), decreased white cell count (6.5%), decreased lymphocyte count (6.5%) and fatigue (6.0%).
Overall, 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment as determined by an independent review. The events were primarily Grade 1 or 2 (10.9%) in severity with one Grade 3 (0.5%) and no Grade 4 events. Four deaths (2.2%) were determined to be due to ILD.
Based on these data, how would you rate the safety profile demonstrated by trastuzumab deruxtecan in this setting? Where 1 = poor and 5 = excellent
1 2 3 4 5
Q. Taking efficacy and safety data into account, how would you rate the clinical profile of trastuzumab deruxtecan overall? Where 1 = poor and 5 = excellent
1 2 3 4 5
Q. Trastuzumab deruxtecan could be approved as a therapy for HER2 positive breast cancer in patients previous treated with Kadcyla (trastuzumab emtansine) next year. Based on the data shared with you today, approximately what percentage of patients in this setting do you think you would ultimately prescribe trastuzumab deruxtecan to?
Results and related analysis will shortly be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.
As always, FirstWord would very much like to receive your feedback and suggestions.
Note: FirstWord Physician Views are a fast-turnaround service to conduct instant polls of up to five questions with guaranteed samples that include physicians from dozens of specialties in major markets. To conduct this poll with a different audience, or an entirely different poll, contact us at email@example.com.
Disclaimer: FirstWord follows market research best practices in conducting its Physician Views polls. However, Physician Views results should be considered directional and clients should use their market research resources for statistical analysis and conclusions required with very high confidence levels.
To read more Physician Views articles, click here.