Breakthrough Clinical Results
Eli Lilly and Company announced that data from several investigational oncology therapies will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. These include imlunestrant (an oral selective estrogen receptor degrader), olomorasib (a KRAS G12C inhibitor), LY4170156 (an antibody-drug conjugate targeting folate receptor alpha), and Verzenio (abemaciclib). Presentations will cover patient-reported outcomes, safety analyses, updated results from Phase 1/2 studies, and initial results from a Phase 1a/1b study. The data presented will span various cancer types, including breast cancer, non-small cell lung cancer, colorectal cancer, and ovarian cancer.
Key Highlights
- Data from imlunestrant, olomorasib, LY4170156, and Verzenio will be presented at ASCO 2025.
- Presentations will include patient-reported outcomes, safety analyses, and updated efficacy data.
- Studies cover various cancer types, including breast, lung, colorectal, and ovarian cancers.
- Data cut-off dates for some abstracts have been updated since initial submission.
Drug used in other indications
Imlunestrant Clinical Trials Beyond Breast Cancer
Based on a thorough review of the provided context, no information is available about imlunestrant being trialed for any indications other than breast cancer. In fact, the context does not contain any references to imlunestrant at all, neither for breast cancer nor for any other conditions.
The context instead provides information about various other breast cancer treatments, including:
- CDK4/6 inhibitors such as palbociclib, ribociclib, and abemaciclib
- mTOR inhibitors like everolimus
- Endocrine therapies including fulvestrant, letrozole, exemestane, anastrozole, and tamoxifen
- Antibody-drug conjugates such as mirvetuximab soravtansine and trastuzumab-deruxtecan
- HER2-targeted therapies including trastuzumab, trastuzumab emtansine (T-DM1), lapatinib, and pertuzumab
The context describes several clinical trials for breast cancer treatments, such as:
- The MonarchE trial: an open-label, randomized, double-blind trial involving 5,637 participants comparing abemaciclib plus endocrine therapy versus endocrine therapy alone for early breast cancer
- A randomized phase 3 trial comparing conventionally fractionated versus hypofractionated whole-breast irradiation with 253 patients
- A randomized controlled trial of moderate-intensity aerobic exercise and diet counseling compared to usual care in triple-negative breast cancer survivors
However, none of these trials involve imlunestrant, and no intervention models for imlunestrant trials are mentioned in the provided context.
Incidence and Prevalence
Global Incidence and Prevalence of Breast Cancer
Breast cancer is the most commonly diagnosed cancer and the leading cause of death in women worldwide. It ranks fifth in the world as a cause of cancer death overall in developed countries and is the second most frequent cause of cancer death in women.
Breast cancer accounts for 29% of malignant tumors. The disease is heterogeneous and differs substantially across different tumors (intertumor heterogeneity) and even within an individual tumor (intratumor heterogeneity).
Four main "intrinsic subtypes" of breast cancer have been identified: - Luminal A - Luminal B - HER2-enriched - Basal-like
Early diagnosis increases 5-year survival rates up to 95%.
Incidence Rates by Ethnicity
The annual incidence rate of all breast cancers was 31.3 (95% CI, 31.2-31.5) per 100,000 people in non-Hispanic White women, which was higher compared with the incidence among Black women.
The incidence rates were lower in: - Asian/Pacific Islander (IRR, 0.90) - American Indian/Alaskan native (IRR, 0.82) - Hispanic White women (IRR, 0.79)
compared to non-Hispanic White women.
Cancer Subtypes by Ethnicity
Black patients had higher incidences of: - HR-positive and ERBB2-positive (IRR, 1.12) - HR-negative and ERBB2-positive (IRR, 1.46) - Triple-negative breast cancer (TNBC) (IRR, 2.07)
compared to non-Hispanic White patients.
Histological Types by Ethnicity
Non-Hispanic White patients had a higher proportion of: - Lobular carcinoma (9.7%) - Tubular adenocarcinoma (0.6%)
compared to: - Black (7.2%; 0.3%) - Asian/Pacific Islander (5.7%; 0.3%) - Hispanic White (7.2%; 0.3%) - American Indian/Alaskan Native patients (7.2%; 0.4%)
In a study of Dutch families at a family cancer clinic, mutations were found in BRCA1 (19%) or BRCA2 (4%) of the families screened.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Breast Cancer
Based on recent publications, several key mechanisms of action are emerging for breast cancer treatment:
Genomic Approaches
- The Breast Multidisciplinary Genomic Tumor Board (MGTB) reviews genomic test results (FoundationOneā¢) for metastatic breast cancer patients to provide more precise care recommendations
- Based on genomic findings, the MGTB mostly recommended clinical trials (34), medical genetics (15), and FDA-approved breast cancer therapies (13)
- Limited actionability of genomic test results was noted as a challenge for the MGTB
Immune System Mechanisms
- High pathological complete response rate is frequently associated with tumor-infiltrating lymphocytes
- Circulating immune cells are linked to chemotherapy response
- Higher pathological complete response rate was observed in patients with baseline relative eosinophil count ā„1.5% (55.6%) versus those with <1.5% (36.2%)
- Improved breast cancer-specific survival was found in patients with high relative eosinophil count or high relative lymphocyte count
- The eosinophil x lymphocyte product (threshold at 35.8) showed associations with pathological complete response, relapse, disease-free survival, and breast cancer-specific survival
Signaling Pathways
- EYA3 protein correlates with decreased survival in breast cancer
- EYA3 regulates metastasis through NF-kB signaling and altered innate immune profile at the pre-metastatic niche
- Secreted CCL2, regulated downstream of EYA3/NF-kB, specifically decreases cytotoxic NK cells in the pre-metastatic niche
- Inhibition of EYA3 could potentially re-activate the innate immune response, inhibiting Triple Negative Breast Cancer metastasis
Therapeutic Approaches
- Neoadjuvant chemotherapy is used in up to 27% of breast cancer patients
- Acceptance and Commitment Therapy (ACT) is being tested for fatigue interference in metastatic breast cancer patients
- Complementary and alternative medicine (CAM) therapies did not alter breast cancer outcomes and should not replace standard treatment