Dr. Jan-Willem Henning (University of Calgary) and Dr. Nadia Califaretti (Grand River Regional Cancer Centre) discuss ESMO 2021 LBA DESTINY Breast03- Second-Line Trastuzumab Deruxtecan for Metastatic HER2-Positive Breast Cancer. Watch their discussion in the video below as they delve into the topic in greater detail.
ESMO LBA1 – Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study
This was the first report of DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized phase 3 study comparing the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC previously treated with trastuzumab and taxane.
- The primary endpoint was PFS by blinded independent central review. Secondary endpoints included OS, objective response rate (ORR), duration of response, PFS by investigator, and safety.
Summary of Results
What data from the trial stands out to you the most?
- The statistically significant and highly clinically meaningful improvement in PFS (primary endpoint).
- Benefits were seen in all evaluated subgroups (including patients with stable brain metastases).
- The toxicity profile of T-DXd was as expected after what was seen in DESTINY Breast 01. Of particular interest, the incidence of ILD and pneumonitis was lower that what has been previously reported in other studies suggesting that with strict criteria for managing it may be less of an issue in practice.
How do you interpret the results seen in the comparator arm (T-DM1)?
- The PFS with the comparator was as expected based on real world data/experience
How will this impact your practice moving forward? How would you sequence and select patients for T-DXd?
- With the highly efficacious outcome, this trial is practice changing and establishes T-DXd as a first choice in this second-line setting
- A multi-disciplinary approach will be necessary as this becomes standard a new standard in second line because of the unique toxicities and potential for infusion related reactions.
- Engagement with pharmacists, nurses, respirologists, and even ophthalmologists in patient management will be important so we can embrace the efficacy seen in this trial .
How does this data compare to recent data with other novel agents? What influences your choice of one therapy over another?
- There has recently been an influx of data and we now have access to several novel agents (i.e. neratinib, ducatinib)
- Other ADC’s are in early phase and have smaller trials so cannot be compared at this point.
- TKI’s have mostly been investigated in later lines and until they are evaluated earlier on we cannot consider/compare them in second line.
In terms of the common adverse events, do you have any comments on how to manage and what to look out for?
- In the trial there were more patients who experiences grade 3 or greater neutropenia, nausea and diarrhea, and alopecia.
- We are used to managing most of the side effects seen and should be able to adapt management in this setting easily.
- Low grade nausea- can be managed with use of antiemetics (typically 5HT3 inhibitor or NK1 inhibitor; always have a rescue antiemetic available for patients). This is now mandated in ongoing trials.
- Neutropenia- requires dose reductions or delays. GCFS may be acquired if warranted/indicated.
- Alopecia- Can be stressful for patients so it is important to manage expectations.
- Important to note that were no deaths associated with these AE’s
- There is great excitement over this data and eagerness to get this into clinical practice and to our patients.
- Analyses of a larger cohort of patients with stable brain mets will provide more information on this important subgroup
- OS data are highly anticipated