Breakthrough Clinical Results
Novartis announced the presentation of data from 60 abstracts at the 2025 ASCO Annual Meeting and EHA 2025 Congress. The data showcases the momentum of their oncology and hematology portfolio, including key drugs like Kisqali, Pluvicto, Scemblix, and Fabhalta. Highlights include new data on Kisqali in pre-menopausal early breast cancer patients, Pluvicto in metastatic castration-resistant prostate cancer, and Scemblix in chronic myeloid leukemia. The company also emphasized its commitment to advancing patient care beyond treatment innovation through partnerships focused on early detection and improved outcomes.
Key Highlights
- New data on Kisqali (ribociclib) in pre-menopausal early breast cancer patients.
- Positive results from Pluvicto (lutetium Lu 177 vipivotide tetraxetan) analyses in metastatic castration-resistant prostate cancer.
- Primary endpoint results of the phase 3b ASC4START trial of Scemblix (asciminib) in chronic myeloid leukemia.
- Fabhalta (iptacopan) data showing clinically meaningful hemoglobin increases in paroxysmal nocturnal hemoglobinuria patients.
Incidence and Prevalence
Early Breast Cancer: Global Incidence and Prevalence
Globally, breast cancer is a significant health concern, with varying incidence and mortality rates across different regions and age groups. While the provided texts offer numerous statistics on breast cancer overall, they lack specific data on early breast cancer incidence and prevalence on a global scale. The information focuses on overall breast cancer or specific demographics (e.g., young women, older adults) or regions (e.g., India, China, US).
Key information extracted from the provided texts regarding overall breast cancer burden:
- 2022: 2.3 million new cases and 670,000 deaths globally.
- 2020: Over 2.3 million new cases and 685,000 deaths globally.
- Projected 2050: New cases and deaths will increase by 38% and 68%, respectively, disproportionately impacting low-HDI countries.
- Projected 2040: The burden is predicted to increase to over 3 million new cases and 1 million deaths annually due to population growth and aging.
Challenges in determining early breast cancer statistics:
- Definition of "early": The provided texts do not consistently define "early breast cancer." It is generally understood as localized or regional disease (stages I-III), but precise definitions can vary.
- Data limitations: Global data on stage at diagnosis is often incomplete, particularly in low- and middle-income countries, making it difficult to isolate early-stage cases.
- Focus on overall burden: The articles primarily focus on the overall burden of breast cancer, rather than specifically on early-stage disease.
Available related information:
- One study assessed the global distribution of breast cancer stage at diagnosis and found that the proportion of cases with distant metastatic breast cancer at diagnosis was high in sub-Saharan Africa (5.6%-30.6%) and low in North America (0.0%-6.0%). This indirectly suggests that the proportion of early-stage diagnoses would be higher in North America and lower in sub-Saharan Africa.
- Another study noted that breast cancer incidence in the US continued an upward trend, largely confined to localized-stage disease. This suggests a rising incidence of early-stage breast cancer in the US, but this is not a global figure.
Conclusion:
While the provided texts offer valuable insights into the overall global burden of breast cancer, they do not provide specific data on the incidence and prevalence of early breast cancer. More research and data collection focusing specifically on stage at diagnosis are needed to accurately quantify the burden of early-stage disease globally. This information is crucial for developing targeted interventions and improving outcomes for women diagnosed with breast cancer.
Emerging Mechanism of Action
Early breast cancer (EBC) encompasses various subtypes, each with distinct molecular characteristics influencing treatment strategies. Recent research emphasizes personalized medicine, tailoring treatment based on individual tumor profiles. Key mechanisms of action (MoAs) emerging for EBC treatment include:
-
CDK4/6 Inhibitors: These agents, like abemaciclib, target cyclin-dependent kinases 4 and 6, crucial for cell cycle progression. Studies show significant improvement in invasive disease-free survival (IDFS) when combined with endocrine therapy in high-risk HR+, HER2- EBC. Notably, abemaciclib plus endocrine therapy resulted in a 2-year IDFS rate of 92.2% compared to 88.7% with endocrine therapy alone.
-
PARP Inhibitors: Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, exploit DNA repair deficiencies in cancer cells, particularly those with BRCA1/2 mutations. OlympiA trial demonstrated significant improvement in overall survival (OS), IDFS, and distant disease-free survival (DDFS) with adjuvant olaparib in patients with germline BRCA1/2 mutations. Four-year OS was 89.8% with olaparib versus 86.4% with placebo.
-
Immunotherapy: Immune checkpoint inhibitors, like pembrolizumab (anti-PD-1), enhance the body's immune response against cancer. KEYNOTE-522 trial showed improved pathological complete response (pCR) and 3-year event-free survival with pembrolizumab plus chemotherapy in high-risk, early-stage triple-negative breast cancer (TNBC). The FDA approved pembrolizumab in this setting.
-
Antibody-Drug Conjugates (ADCs): ADCs, like trastuzumab deruxtecan (T-DXd), deliver potent chemotherapy directly to cancer cells, minimizing systemic toxicity. DESTINY-Breast04 trial demonstrated T-DXd's efficacy in HER2-low breast cancer, offering a new standard of care for these patients.
-
De-escalation of Therapy: Research focuses on identifying patients who can safely omit certain treatments, like axillary lymph node dissections or radiotherapy, without compromising outcomes. This approach minimizes treatment-related morbidity and improves quality of life.
-
Targeted Therapies: Research continues to explore novel targets and agents, including AKT inhibitors (e.g., capivasertib) and CSF1R inhibitors (e.g., pexidartinib), to personalize treatment based on specific molecular alterations.
In addition to these MoAs, ongoing research investigates the role of circulating tumor DNA (ctDNA) as a prognostic and predictive biomarker, and the potential of liquid biopsies for real-time monitoring of tumor dynamics. These advancements contribute to the evolution of personalized medicine in EBC, aiming to optimize treatment efficacy and minimize adverse effects.
Drug used in other indications
Kisqali (ribociclib), primarily known for treating HR+/HER2- breast cancer, is also being investigated for other cancer types. Several trials are exploring its potential in various settings and combinations:
Advanced Breast Cancer:
- Combination with other targeted therapies: Studies are evaluating ribociclib with agents like everolimus (mTOR inhibitor), encorafenib, and nazartinib in patients with advanced breast cancer, particularly those with HR+/HER2- subtypes. These trials aim to enhance efficacy and overcome resistance to endocrine therapy. One example is the TRINITI-1 trial, which investigated ribociclib in combination with everolimus and exemestane in patients with HR+, HER2- advanced breast cancer after progression on a CDK4/6 inhibitor.
- Specific patient populations: Research is ongoing to assess ribociclib's efficacy in male patients with HR+/HER2- advanced breast cancer. The COMPLEEMENT-1 trial included male patients and demonstrated similar efficacy and safety to the overall population, supporting its use in this group.
- Sequencing strategies: Trials are exploring the use of ribociclib after progression on other CDK4/6 inhibitors. The AMICA study evaluated ribociclib plus endocrine therapy as maintenance treatment after chemotherapy in HR+/HER2- metastatic breast cancer, showing promising efficacy and safety.
Other Cancer Types:
- Ovarian and Endometrial Cancers: A phase II trial investigated ribociclib with letrozole in relapsed estrogen receptor-positive ovarian and endometrial cancers. Promising activity was observed, especially in low-grade serous ovarian cancer and grades 1 and 2 endometrial cancer.
- Prostate Cancer: The LEEP trial assessed the pharmacodynamic effects of ribociclib in men with high-risk, localized prostate cancer undergoing radical prostatectomy. The primary endpoint was a reduction in the Ki-67 proliferation index.
- Advanced Solid Tumors and Lymphomas: Early-phase trials have investigated ribociclib in patients with Rb-positive advanced solid tumors or lymphomas, showing an acceptable safety profile and preliminary signs of clinical activity.
Intervention Models:
The intervention models in these trials vary depending on the cancer type and setting. They include:
- Combination therapy: Ribociclib is often combined with other targeted therapies or endocrine therapy to enhance efficacy and overcome resistance mechanisms.
- Monotherapy: In some cases, ribociclib is evaluated as a single agent, particularly in patients who have progressed on other therapies.
- Neoadjuvant and adjuvant settings: Trials are exploring the use of ribociclib in earlier stages of cancer, either before or after surgery, to improve disease-free survival.
- Maintenance therapy: Ribociclib is also being investigated as maintenance therapy after chemotherapy to prolong the duration of response.
- Different dosing schedules: Studies are evaluating various ribociclib dosing schedules, including continuous and intermittent dosing, to optimize efficacy and tolerability.
These trials aim to expand the therapeutic potential of ribociclib beyond its current indications and improve outcomes for patients with various cancer types.