fulvestrant / Generic mfg. - LARVOL DELTA

Circulating tumor cells (CTCs) dynamics after CDK4/6i for hormone-receptor positive (HR+) metastatic breast cancer (MBC): A biomarker analysis of the PACE randomized phase II study. (ASCO 2023) - P2 | "Background: PACE is a multicenter randomized phase II trial investigating palbociclib (P) in combination with fulvestrant (F) after progression on any CDK4/6 inhibitor (CDK4/6i), with or without the PD-L1 inhibitor avelumab (A), in HR+/HER2- MBC. Baseline CTC enumeration is prognostic in patients receiving F with or without CDK4/6i. The StageIVaggressive subgroup may derive preferential benefit with combinations of F+P or F+P+A over F alone. Findings should be confirmed in other studies."

Biomarker • Circulating tumor cells • Clinical • IO biomarker • Metastases • P2 data • Tumor cell • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CTCs • HER-2

Dalpiciclib plus letrozole or anastrozole as first-line treatment for HR+/HER2- advanced breast cancer (DAWNA-2): A phase III trial (ESMO 2022) - P3 | "Clinical trial identification NCT03966898. Conclusions Adding dalp to letrozole/anastrozole significantly prolonged PFS in HR+/HER2- ABC, with manageable toxicities. Dalp is the 4 th CDK4/6 inhibitor showing survival benefit with letrozole or anastrozole in untreated HR+/HER2- ABC, or with fulvestrant in pretreated HR+/HER2- ABC, in addition to palbociclib, ribociclib and abemaciclib."

Clinical • Late-breaking abstract • P3 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Time to next treatment to evaluate the therapeutic sequence after first- or second-line CDK4/6 inhibitors of hormone receptor-positive, HER2-negative advanced breast cancer in Italy: a retrospective/prospective observational trial GOIRC-04-2019. (PubMed, ESMO Real World Data Digit Oncol) - "Palbociclib, ribociclib, and abemaciclib are approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (aBC), in combination with aromatase inhibitors or fulvestrant...Subsequent therapies, including chemotherapy (CT), endocrine therapy (ET) with or without everolimus, and CDK4/6i-based regimens, were evaluated...These findings emphasize the variability in treatment efficacy following CDK4/6i therapy and underscore the importance of personalized treatment strategies. Further research is needed to optimize therapeutic sequences and improve patient outcomes in this setting."

Journal • Observational data • Retrospective data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. (ASCO 2022) - P2 | "In terms of prior CDK 4/6i, 100 pts previously received palbociclib (84%), 13 pribociclib (11%), 2 abemaciclib (2%), and 4 palbociclib and another CDK 4/6i (3%). In this randomized, placebo-controlled trial, there was a significant PFS benefit for pts with HR+/HER2- MBC to switch ET and receive ribociclib after progression on CDK 4/6i."

Clinical • Late-breaking abstract • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Efficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial). (PubMed, J Immunother Cancer) - "Although the combination of nivolumab and abemaciclib was active, it caused severe and prolonged immune-related AEs."

Biomarker • Combination therapy • IO biomarker • Journal • Metastases • P2 data • Breast Cancer • Hematological Disorders • Hepatitis C • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Interstitial Lung Disease • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • CD8 • HER-2

Imlunestrant (Imlu) with or without abemaciclib (Abema) in advanced breast cancer (ABC): A subgroup analysis in CDK4/6 inhibitor (CDK4/6i)-pretreated patients (pts) from EMBER-3 (ESMO-BC 2025) - P3 | "The EMBER-3 trial reported significant PFS improvement with imlu over standard therapy (SOC; fulvestrant [fulv] or exemestane) in pts with ESR1 mutations (m), as well as with imlu + abema over imlu in all pts, regardless of ESR1m. In pts with ER+, HER2- ABC who have progressed on prior CDK4/6i, imlu+abema showed a consistent benefit over imlu, regardless of clinico-genomic factors. EMBER-3 is the 1st phase III trial to show benefit of an oral SERD + CDK4/6i after disease progression on prior CDK4/6i."

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Ribociclib (RIB) vs. palbociclib (PAL) in patients (pts) with hormone receptor-positive/HER2-negative/HER2-enriched (HR+/HER2-/HER2-E) advanced breast cancer (ABC): A head-to-head phase III study—HARMONIA SOLTI-2101/AFT-58. (ASCO 2023) - P3 | "HER2-E cohort will randomized pts 1:1 to RIB+ET (letrozole or fulvestrant) or PAL+ET. As per recent protocol amendment, BL cohort pts will be treated with paclitaxel plus tislelizumab, an anti PD-1 monoclonal antibody, pts may be offered to try RIB + ET first, and will remain eligible for paclitaxel + tislelizumab upon progression...HARMONIA will recruit in Spain (55 sites), Portugal (5), and US (35) within SOLTI & AFT network. Clinical trial information: NCT05207709."

Clinical • Head-to-Head • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

MONARCH plus: A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer (clinicaltrials.gov) - P3 | N=463 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Jan 2027 ➔ Mar 2028

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Combination of olaparib, durvalumab and fulvestrant in patients with advanced ER+/HER2- breast cancer and selected genomic alterations: results of the DOLAF trial. (PubMed, Clin Cancer Res) - P2 | "In patients with ER+/HER2- metastatic breast cancer and selected genomic alterations, this triplet combination was active and had an acceptable toxicity profile (NCT04053322)."

IO biomarker • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • BRCA1 • ER • HER-2 • HRD • MSI

Thymidine kinase activity as a prognostic and predictive biomarker in the Phase II PACE trial of CDK4/6 inhibition beyond progression (SABCS 2024) - P2 | "Methods The PACE (NCT03147287) multicenter phase II trial randomized 220 pts with ER+, HER2- MBC who had progressed on at least 6 months (mo) of prior CDK4/6i and aromatase inhibitor (AI) to receive fulvestrant alone (F), F plus palbociclib (F+P), or F+P plus the PD-1 inhibitor avelumab (F+P+A). However, high C2D1 on-treatment TKa was associated with inferior outcomes. Early dynamic changes in TKa levels may allow identification of populations with distinct prognoses, possibly facilitating clinical decisions in this context."

Biomarker • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • ER • HER-2

A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread (clinicaltrials.gov) - P1 | N=198 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK6 • HER-2

Camizestrant in combination with three globally approved CDK4/6 inhibitors in women with ER+, HER2- advanced breast cancer: Results from SERENA-1. (PubMed, Clin Cancer Res) - P1 | "Camizestrant is well-tolerated, with anti-tumor activity in combination with CDK46i. These results support evaluation of camizestrant 75 mg plus standard CDK4/6i doses in Phase 3 trials."

Journal • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2

AFT-38 PATINA: a Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Saftey of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy after Induction Treatment for Hormone Receptor-Positive (HR+)/HER-Positive Metastatic Breast Cancer (SABCS 2024) - " PATINA is a randomized, open-label, international Phase III trial assessing palbociclib in combination with anti-HER2 and ET during first-line treatment for HR+/HER2+ metastatic breast cancer (MBC) after completion of 6-8 cycles of induction chemotherapy plus trastuzumab plus pertuzumab (HP) or trastuzumab (H) without evidence of progression...ET options included aromatase inhibitor (AI) or fulvestrant, with ovarian suppression required for premenopausal patients... The AFT-38 PATINA Phase III trial demonstrated a clinically meaningful 15.2-month PFS improvement with palbociclib added to anti-HER2 plus ET, with a manageable toxicity profile, and may represent a new standard of care for patients diagnosed with HR+ HER2+ advanced breast cancer."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer

Primary outcome analysis of the phase 3 SONIA trial (BOOG 2017-03) on selecting the optimal position of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). (ASCO 2023) - P3 | "Patients were randomized 1:1 to receive strategy A (first-line treatment with an NSAI + CDK4/6i, followed on progression by fulvestrant (F)) or strategy B (first-line treatment with an NSAI, followed on progression by F + CDK4/6i). Choice between one of the available CDK4/6i (abemaciclib, palbociclib, ribociclib) was a stratification factor and left to the discretion of the treating physician... First-line use of CDK4/6i + ET does not provide statistically significant, nor clinically meaningful PFS benefit compared to second-line use in women with HR+, HER2- ABC. Use in first-line prolongs the time on CDK4/6i by 16.4 months and increases toxicity and costs. Second-line use may thus be a preferred option for the majority of patients."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Primary results from a phase 2a study of zanidatamab (zani) + palbociclib (palbo) + fulvestrant (fulv) in HER2+/HR+ metastatic breast cancer (mBC) (SABCS 2023) - P2 | " Eligible pts had HER2+ (by local HER2 testing) and HR+, unresectable, locally advanced or mBC; ECOG PS ≤1; prior treatment with at least trastuzumab, pertuzumab, and T-DM1; and no prior CDK4/6 inhibitor...In the metastatic setting, pts received a median (range) of 4 (1-12) prior systemic regimens, 3 (1-10) prior different HER2-targeted therapies, and 1 (0-5) prior endocrine therapy; 12 (24%) pts had prior T-DXd and 11 (22%) had prior fulv... Zani + palbo + fulv showed a promising PFS6 and mPFS with durable responses. The safety profile was manageable. These results support further development of a novel chemotherapy-free treatment regimen for heavily pretreated pts with HER2+/HR+ mBC."

Late-breaking abstract • Metastases • P2a data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Circulating tumor cells dynamics after CDK4/6 inhibitor for hormone-receptor positive metastatic breast cancer: a biomarker analysis from the PACE phase II study. (PubMed, Clin Cancer Res) - "Baseline CTC enumeration provides significant prognostic information in HR+/HER2- MBC. StageIV aggressive patients derive greater benefit from F+P or F+P+A over F alone, independent of clinical or ctDNA features. This highlights the potential of to guide treatment decision-making."

Biomarker • Circulating tumor cells • Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CTCs • HER-2

Open-label, randomized study of lasofoxifene (LAS) vs fulvestrant (Fulv) for women with locally advanced/metastatic ER+/HER2- breast cancer (mBC), an estrogen receptor 1 (ESR1) mutation, and disease progression on aromatase (AI) and cyclin-dependent kinase 4/6 (CDK4/6i) inhibitors (ESMO 2022) - P2 | "Clinical trial identification NCT03781063. LAS may be a new treatment option following endocrine/CDK4/6i therapies if efficacy is confirmed in a larger, adequately powered clinical study. A phase 3 combination study of LAS and abemaciclib is planned based on encouraging efficacy/safety in ELAINE 2."

Clinical • Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Baseline ctDNA and methylation status as predictors of treatment benefit in the phase III post MONARCH trial of abemaciclib + fulvestrant in advanced breast cancer patients (ESMO-BC 2025) - P3 | "Within multiple biomarker subgroups, abemaciclib had consistent benefit. These exploratory results are hypothesis generating and offer further insight into the use of abemaciclib + fulvestrant as a treatment option for HR+, HER2- ABC after progression on CDK4/6i."

Circulating tumor DNA • Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-Negative Metastatic Breast Cancer. (PubMed, J Clin Oncol) - "The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population."

Journal • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial. (ASCO 2024) - P3 | "Prior CDK4/6i was 59% palbociclib, 33% ribociclib, and 8% abemaciclib. Abemaciclib + fulvestrant demonstrated statistically significant PFS improvement in pts with ABC progression on prior CDK4/6i-containing therapy."

Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Camizestrant in combination with capivasertib for women with ER-positive, HER2-negative advanced breast cancer: results from SERENA-1. (PubMed, ESMO Open) - P1 | "In these pretreated participants, camizestrant 75 mg in combination with capivasertib 400 mg was well tolerated, with a side effect profile consistent with each drug as monotherapy, and showed encouraging evidence of clinical efficacy."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • PIK3CA • PTEN

Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study. (ASCO 2024) - P1 | "Key eligibility (Part C): ≥ 2 prior HER2 directed regimens, no prior CDK4/6i or fulvestrant; (Part E): received 1 st line induction taxane chemotherapy (any duration) + H + P, without disease progression and ≤1 prior therapy for aBC. Imlunestrant in combination with trastuzumab ± abemaciclib or pertuzumab was well tolerated, showed no drug-drug interactions, and demonstrated preliminary antitumor activity in pts with ER+/HER2+ aBC."

Combination therapy • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Pain • Neutropenia • Oncology • Solid Tumor • CDK4 • ER • GATA3 • PIK3CA • TP53

Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

MCC-20899: Stereotactic Radiation & Abemaciclib in the Management of HR+/HER2- Breast Cancer Brain Metastases (clinicaltrials.gov) - P1/2 | N=31 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Final overall survival (OS) for abemaciclib plus trastuzumab +/- fulvestrant versus trastuzumab plus chemotherapy in patients with HR+, HER2+ advanced breast cancer (monarcHER): A randomized, open-label, phase II trial (ESMO 2022) - P2 | "Updated PFS and safety findings were consistent with the primary analysis (data cutoff 8 Apr 2019). Conclusions Abemaciclib plus trastuzumab ± fulvestrant numerically improved OS in women with HR+, HER2+ ABC compared to chemotherapy plus trastuzumab with a manageable safety profile."

Clinical • Late-breaking abstract • P2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2