Breast cancer ranks as the most prevalent cancer globally and stands as the leading contributor to cancer-related fatalities. Among the various types of breast cancer, there exists a particularly aggressive subtype known as triple-negative breast cancer (TNBC). TNBC distinguishes itself by testing negative for estrogen receptors, progesterone receptors, and the overexpression of the human epidermal growth factor receptor 2 (HER2). Approximately 15% of breast cancer cases fall into the category of triple-negative, which is known for its aggressive nature. When it comes to the initial treatment of advanced or metastatic TNBC, it typically involves chemotherapy either as a standalone therapy or in conjunction with immunotherapy. 

Datopotamab deruxtecan (Dato-DXd) is a groundbreaking TROP2-directed Antibody-Drug Conjugate (ADC), designed with Daiichi Sankyo's state-of-the-art DXd ADC technology. It stands out as one of the lead ADCs in Daiichi Sankyo's oncology pipeline and is a flagship program within AstraZeneca's ADC scientific platform. Comprising a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, it is linked to topoisomerase I inhibitor payloads through cleavable linkers.

The investigation of Datopotamab deruxtecan in combination with durvalumab as a first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer is currently underway in the BEGONIA trial. BEGONIA (NCT03742102) is an ongoing 2-part, open-label platform study in 1L a/mTNBC, evaluating durvalumab, an anti–PD-L1 antibody, plus novel therapies, including Dato-DXd, an antibody-drug conjugate made of an anti-TROP2 antibody covalently linked via a cleavable linker to a topoisomerase I inhibitor payload. Early data from BEGONIA Arm 7, Dato-DXd + durvalumab, showed promising responses. 

As of February 2, 2023, 62 patients received Dato-DXd + durvalumab treatment, with 29 still undergoing it. The median follow-up reached 11.7 months. Impressively, a confirmed objective response rate of 79% was observed, with 10% achieving complete responses and 69% experiencing partial responses. Notably, the treatment's efficacy was consistent across varying PD-L1 expression levels. The median duration of response stood at 15.5 months, and the median Progression-Free Survival was 13.8 months. Encouragingly, no new safety concerns emerged during the study. 

Advances in treating initial advanced triple-negative breast cancer have seen limited progress over the years. Novel therapeutic approaches are imperative to enhance outcomes for patients battling this aggressive breast cancer subtype. The recent findings from the BEGONIA trial strengthen the company's belief in datopotamab deruxtecan's potential to emerge as a pivotal treatment option in this setting.

KOL insights

“They show very promising activity, not only in terms of ORR, which was even higher than had previously been reported – 79% versus 74% – but also for PFS, where 13.8 months for TNBC in the first-line setting is really appealing.”– Professor from Institut Gustave Roussy, Villejuif, France.

Conclusion: For individuals facing triple-negative breast cancer, the sobering reality is the potential for disease progression post-initial treatment, highlighting the critical need for more enduring therapeutic options. The BEGONIA findings illuminate the promise of datopotamab deruxtecan in previously untreated advanced triple-negative breast cancer. As per Delveinsight’s estimates, we expect this TROP-2 ADC to generate a revenue of approximately USD 150 million by 2032 in TNBC, however this revenue is expected to increase beyond 2032 considering that this ADC is expected to launch by 2027 in this indication. In addition to TNBC, HR+/HER2- metastatic Breast cancer is another lucrative opportunity for this therapy, where we expect it to generate approximately USD 1.2 billion in revenue in 7MM by 2032, considering that HR+/HER2- Breast cancer is a much larger addressable patient pool.

These results add to the growing body of evidence supporting the utility of this TROP2-directed antibody-drug conjugate in various breast cancer subtypes when used in combination therapies.

The synergy of Dato-DXd and durvalumab continues to exhibit manageable safety profiles and remarkable, sustained response rates in first-line advanced/metastatic TNBC. Results from the ongoing phase Ib/II BEGONIA platform trial affirm the potential of this anti-TROP2 ADC for the initial treatment of unresectable, locally advanced/metastatic TNBC. Among the 62 patients treated, a confirmed objective response rate (ORR) of 79% was achieved, including six complete responses, independent of tumor PD-L1 expression. The median duration of response reached 15.5 months, and the median progression-free survival (PFS) extended to 13.8 months. The most frequent adverse events were nausea and stomatitis, with 57% of patients experiencing grade 3-4 adverse events, and 23% reporting serious adverse events. Rates of anemia, diarrhea, and neutropenia were low. Three patients experienced grade 2 treatment-related interstitial lung disease (ILD)/pneumonitis, and fortunately, there were no treatment-related adverse event-related deaths. However, 16% of patients had to discontinue treatment due to adverse events.

Beyond the BEGONIA program, datopotamab deruxtecan is under evaluation in ongoing trials such as TROPION Breast02 and TROPION-Breast03. AstraZeneca is also actively researching a potential diagnostic test to identify the patients who stand to benefit most from treatment with datopotamab deruxtecan. These advancements hold the promise of transforming the landscape of triple-negative breast cancer treatment. 

According to the DelveInsight estimates the total incident population of TNBC in the 7MM was approximately 100,000 in 2022. Among the 7MM countries, Spain accounted for the least number of incident cases of TNBC i.e., 5,100 cases in 2022.

For more insight into the patient’s burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Triple Negative Breast Cancer (TNBC) - Market Insights, Epidemiology, and Market Forecast Report.