Gilead and Kite Present New Cancer Data at ESMO 2025, Highlighting Trodelvy's Potential in Metastatic TNBC
Breakthrough Clinical Results
Gilead and Kite will present new data at the ESMO 2025 Congress, showcasing progress in cancer treatment. Key highlights include Phase 3 ASCENT-03 study results for Trodelvy as a first-line treatment for metastatic triple-negative breast cancer (TNBC) in patients not eligible for PD-1/PD-L1 inhibitors, demonstrating a significant improvement in progression-free survival compared to chemotherapy. Additionally, overall survival results from the EDGE-Gastric study evaluating domvanalimab plus zimberelimab and chemotherapy in advanced gastric or esophageal cancer will be shared. The presentations underscore Gilead's strategy of advancing innovative therapies into earlier lines of treatment and expanding the types of cancer they can treat.
Key Highlights
- ASCENT-03 study shows Trodelvy significantly improves progression-free survival in first-line metastatic TNBC patients ineligible for PD-1/PD-L1 inhibitors.
- EDGE-Gastric study reveals promising overall survival results for domvanalimab plus zimberelimab and chemotherapy in advanced gastric or esophageal cancer.
- ASCENT-04 study evaluates quality of life with Trodelvy plus Keytruda versus Keytruda and chemotherapy in first-line PD-L1+ metastatic TNBC.
- Multiple abstracts accepted at ESMO 2025 covering breast, gastric, esophageal, lung, and head and neck cancers.
Incidence and Prevalence
Latest Global Estimates of Breast Cancer Incidence and Prevalence
Breast cancer remains the most common female malignancy in both developing and developed countries and is the primary cause of death among women globally. Recent global statistics paint a concerning picture of the disease's burden worldwide.
Global Incidence
In 2022, approximately 2.3 million new cases of female breast cancer occurred globally, with 670,000 deaths attributed to the disease. This follows similar numbers from 2020, when 2.3 million women were diagnosed and 685,000 died of breast cancer worldwide.
The incidence rates continue to increase and do so more rapidly in countries that historically had low rates. Studies show that annual incidence rates increased by 1-5% in half of the countries examined. Alarmingly, the number of diagnoses is projected to increase to 3 million per year by 2040.
Regional Variations
Regional data shows significant variations:
- In Taiwan (2017 data), breast cancer prevalence was 834.37 per 100,000 persons (95% CI, 829.28-839.45) and incidence was 93.00 per 100,000 person-year (95% CI, 91.27-94.73)
- In Botswana, overall breast cancer prevalence was calculated to be 18/10,000 (95% CI, 8 to 29/10,000)
- In Egypt's Gharbiah Province, there was a three to four times higher urban incidence of breast cancer compared to rural areas
- In the United States, persistent geographic disparities exist, with 219 counties identified as persistent hot spots for late-stage breast cancer diagnosis
Trends by Demographic Groups
Recent trends show breast cancer appears to be increasing in certain subgroups:
- Non-Hispanic blacks had a 2.0% annual percentage change from 2005 to 2009
- Asian/Pacific Islanders showed a 1.2% annual percentage change from 2000 to 2009
- ER-positive breast cancer significantly increased in almost all age/race sub-groups after 2005
- Conversely, ER-negative breast cancer decreased in most sub-groups
Future Projections
The future outlook is concerning. By 2050, new cases and deaths will have increased by 38% and 68%, respectively, disproportionately impacting low-HDI (Human Development Index) countries. Despite the availability of new drugs and novel treatment combinations, it is postulated that the incidence and mortality of breast cancer will rise by 40.8% and 51.9% respectively by 2040.
Mortality Trends
While mortality rates decreased in 29 countries with very high Human Development Index (HDI), only seven countries (for example, Belgium and Denmark) are meeting the Global Breast Cancer Initiative goal of at least a 2.5% decrease in mortality each year.
In Türkiye, from 1990 to 2009, the breast cancer mortality rates tended to increase from 12.26/105 in 1990 to 12.65/105 in 2019, with mortality attributed to modifiable factors increasing by 3% from 1990 (20.4%) to 2019 (23.1%).
These statistics underscore the need for continued global efforts in breast cancer prevention, early detection, and treatment strategies to address this growing public health challenge.
Key Unmet Needs and Targeted Populations in Breast Cancer (2022-2024)
Major Challenges and Unmet Needs
The biggest challenges in breast cancer treatment remain metastasis and drug resistance, requiring ongoing molecular evaluation and screening of therapeutic targets. Triple-negative breast cancer (TNBC) continues to be a most deadly human malignancy with limited response to current therapies. Similarly, Metaplastic carcinoma of breast (MCB) has no specific treatment guidelines and carries a poor prognosis.
Accurate patient selection for immunotherapy remains a major challenge, with needs for better methods to analyze samples and evaluate immunogenicity. There is also demand for targeted drugs that are less toxic and more effective against breast cancer.
The COVID-19 pandemic created additional challenges, with screening restrictions leading to fewer diagnoses during early phases. When patients did present during screening moratoriums, they were younger, more likely to be black, had higher BMI, and more frequently had HER2-positive tumors.
Targeted Populations
Several specific patient populations are being targeted for interventions:
- Patients with aggressive triple-negative breast cancers that are immunogenic, exhibit resistance to chemotherapy and have poor prognosis
- Patients with high expression of NSMCE2 and MAL2 genes, which correlate with poor prognosis
- Patients with aberrant Tissue Factor (TF) expression who had poor prognosis and low immune effector cell infiltration
- Patients with TP53 mutations, mostly seen in triple-negative breast cancer
- HER2-positive patients with small tumors (pT1a,b N0M0), leptomeningeal metastases, or who progressed after pertuzumab-containing therapy
- TNBC patients with PD-L1-positive/TILs-low tumors who have poor prognosis
- Patients with hormone receptor-positive (HR)/HER2-negative breast cancers, where recurrence remains a pivotal challenge
Emerging Therapeutic Approaches
Research is focusing on several promising approaches:
- Targeting the tumor microenvironment factors that lead to immune system suppression
- Using Interleukin-1 cytokines as therapeutic targets, especially for metastatic breast cancer
- Super-enhancer disruption to target genes like NSMCE2, associated with poor response to chemotherapy
- Anti-TF antibodies and dual-targeting anti-TF&TGFβR fusion proteins to improve tumor immunoenvironment
- Kuwanon C, an isoamylated flavonoid, as a less toxic targeted drug
- Combination treatment with ABL allosteric inhibitors and EZH2 inhibitors for TNBC
- Pathway-specific therapies based on relapse patterns: RTK inhibitors for primary resistant groups, mTOR and CDK4/6 inhibitors for secondary resistant groups
Socioeconomic Factors
Research has identified that historical redlining (mortgage lending discrimination) is associated with breast cancer outcomes, but only among non-Latina White women. For these women, residence in historically favored areas correlates with lower odds of late-stage diagnosis, high tumor grade, triple-negative subtype, and breast cancer-specific death. However, these associations were not found among non-Latina Black or Latina women, highlighting persistent disparities.
Recent Studies
Recent Breast Cancer Studies: Interventions, Safety, and Efficacy
DESTINY-Breast02 (2024)
This study evaluated trastuzumab deruxtecan in patients with HER2-positive unresectable or metastatic breast cancer. Patients receiving this intervention demonstrated superior progression-free and overall survival compared to those receiving treatment of physician's choice. The median time to definitive deterioration was delayed with trastuzumab deruxtecan (14.1 months vs 5.9 months). The study showed a hazard ratio of 0.5573, indicating significant improvement in quality of life measures.
CDK4/6 Inhibitors Meta-Analysis (2023)
This meta-analysis examined CDK4/6 inhibitors combined with endocrine therapy for HR-positive and HER2-negative advanced breast cancer. The addition of CDK4/6 inhibitors significantly prolonged overall survival (HR 0.76) and progression-free survival (HR 0.56). The treatment group also showed improved overall response rate (RR 1.43), clinical benefit rate, and time to chemotherapy. These results demonstrate substantial efficacy benefits for this combination therapy.
OLIGOMA-Trial (2023)
This randomized controlled multi-national multi-center therapeutic confirmatory trial is studying local ablative radiotherapy as an additive treatment in patients with oligometastatic breast cancer receiving standard systemic therapy. Patients are randomized 1:1 to standard systemic therapy with or without radiotherapy to all metastatic sites. The trial includes patients with up to five metastatic lesions, including those with up to three brain metastases and locoregional recurrence. Co-primary endpoints are progression-free survival and quality of life.
Docetaxel-Trastuzumab (TH) Regimen Study (2025)
This retrospective analysis of the docetaxel-and-trastuzumab regimen in early-stage HER2-positive breast cancer showed impressive efficacy outcomes with a 5-year disease-free survival rate of 96.5% and an overall survival rate of 98.6%. Among the five patients who experienced invasive disease events or death, three had local or regional recurrences.
Pertuzumab Safety Study (2025)
This study assessed the safety of pertuzumab with trastuzumab-based therapy for HER2-positive breast cancer. When compared to trastuzumab alone, the combination showed increased signals for gastrointestinal disorders (ROR: 1.45), particularly diarrhea (ROR: 3.49), infections and infestations (ROR: 1.54), and skin disorders (ROR: 1.63). The frequency of adverse events causing or prolonging hospitalization increased with the combination therapy (ROR: 1.18).
Maharishi Amrit Kalash (MAK) Study (2023)
This systematic review of randomized controlled trials investigated the effects of MAK in breast cancer patients receiving chemotherapy. The intervention showed beneficial effects on performance status, anorexia, vomiting, and body weight. Notably, none of the studies reported adverse events, suggesting MAK may have supportive effects in chemotherapeutic treatments for breast cancer patients with a favorable safety profile.
