With the advancement of breast cancer treatment, there are increasingly more life-saving drugs available for patients. The emergence of new treatment methods is like a relay race, passing on the hope of life, even in the face of recurrence and metastasis, it is no longer a dead end. In the past, anti-HER2 treatments saved countless lives, but only HER2 positive patients could benefit. However, research has found that patients who were originally HER2 negative can also benefit from new anti-HER2 treatments. What is the reason behind this?
Let me explain this in detail.
Previously, we determined the HER2 status in breast cancer simply by distinguishing between “positive” and “negative”. The determination method is as follows: HER2 positive is defined as IHC3+ or IHC2+/FISH+, while HER2 negative is IHC2+/FISH- or IHC1+ or IHC0. Only HER2 positive patients could benefit from traditional anti-HER2 treatment, while HER2 negative patients could only be treated based on hormone receptor status, categorized as hormone receptor positive (Luminal type) or hormone receptor negative (triple-negative). However, the emergence of DS-8201 (trastuzumab deruxtecan) has changed this treatment landscape, allowing those with “low HER2 expression” (IHC2+/FISH- or IHC+) to achieve breakthrough treatment benefits. This means that as long as a patient’s HER2 pathological test shows a “+”, they may qualify for treatment with DS-8201 and benefit from it!
It is worth mentioning that at last year’s SABCS conference, the DESTINY-Breast 04 study (DB04) announced groundbreaking research progress for patients with low HER2 expression, bringing significant good news for breast cancer patients! It is the first Phase III clinical study to evaluate HER2 targeted drugs in patients with metastatic HER2 low expression breast cancer, exploring the efficacy and safety of DS-8201 compared to physician’s choice of chemotherapy in patients with HER2 low expression. The results of this study were announced at the conference, showing the treatment outcomes for different types of patients. So, which patient groups benefit more from it? Let me share that with you next.
01
What types of patients participated in the study (baseline characteristics)?
Let’s first look at the characteristics of the patients who participated in the study. Unlike previous anti-HER2 treatments that were only used for patients with high HER2 expression, the DB04 study included patients with the following characteristics:
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Since 40% of the enrolled population is Asian, this study population is more representative of the Chinese population;
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The enrolled population includes both those who have used CDK4/6 inhibitors and those who have not, which aligns with the medication situation of most recurrent patients in clinical practice.
Considering these characteristics, we can see that the study population is representative of the Chinese situation and aligns with the previous treatment experiences of patients, making the research results more meaningful for our reference.
02
How effective is the treatment for different patient situations (subgroup analysis)?
Factors that may affect efficacy include: HER2 status, previous treatment history, age, etc. I found that although each patient participating in this study had different HER2 statuses, previous treatment histories, and ages, the trial results showed that these factors did not affect the efficacy of DS-8201.
The results of this trial showed that: the treatment outcomes of different types of patients receiving DS-8201 were consistent with the overall population, and whether or not they had previously used CDK4/6 inhibitors, the rapid progression of disease or tumor burden status did not affect efficacy. Compared to the physician’s choice of chemotherapy, patients in any disease burden status could benefit, especially those with high disease burden (≥3 metastatic sites) who could benefit even more from DS-8201; additionally, the incidence of treatment-related interstitial lung disease (ILD) with DS-8201 was similar regardless of previous use of CDK4/6 inhibitors. Previous use of CDK4/6 inhibitors itself poses a risk of ILD, but using DS-8201 did not increase the incidence of ILD.
03
If there is a +, there is hope
Before the results of the DB04 study were announced, clinicians generally treated advanced patients with low HER2 expression as HER2 negative. HR+/HER2- patients primarily received endocrine therapy or endocrine combination therapy as the main treatment strategy; HR-/HER2- patients mainly received immune checkpoint inhibitors (PD-1/PDL-1), trastuzumab, etc., as the main treatment strategy, but the efficacy benefits were very limited. However, the results of the DB04 trial showed:
In the HR positive population, compared to the control group, the DS-8201 group achieved a median progression-free survival (mPFS) of 10.1 months (vs 5.4 months), reducing the risk of death or progression by 49%. The mPFS for those who had previously used CDK4/6 inhibitors or not was 10 months and 11.7 months, respectively. Compared to the control group, the DS-8201 group improved median overall survival (mOS) by 6.4 months (23.9 vs 17.5), reducing the risk of death by 36%.
In the HR negative population, the mPFS for DS-8201 increased nearly threefold (8.5 vs 2.9), reducing the risk of disease progression or death by 54%. Compared to the control group, the DS-8201 group improved mOS by 6.6 months (23.4 vs 16.8), reducing the risk of death by 36%.
In the overall population, DS-8201 significantly improved mPFS (months) to 9.9 (vs 5.1), reducing the risk of disease progression or death by 50%. Therefore, overall, for HR+ or HR- HER2 low expression patients, DS-8201 is currently the ADC drug with the greatest survival benefit, providing new treatment options for this group of patients. As long as there is a “+” in HER2 status, they may benefit from DS-8201, giving patients new hope for treatment!We hope that new treatment drugs can benefit more patients, allowing the baton of life to continue to be passed on!
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