exemestane / Generic mfg. - LARVOL DELTA

Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): Updated efficacy results from the phase 3 EMBER-3 trial (SABCS 2025) - "Background: At the primary progression-free survival (PFS) analysis, the phase 3 EMBER-3 trial in patients (pts) with ER+, HER2- ABC demonstrated significant PFS benefit with imlunestrant (imlu) vs standard therapy (SOC: fulvestrant or exemestane) in pts with ESR1 mutations (ESR1m), and with imlunestrant+abemaciclib (imlu+abema) vs imlu in all pts, regardless of ESR1m status. At a median follow-up of 28.5 months, a clinically meaningful improvement in OS was observed with imlu vs SOC in pts with ESR1m (corresponding to a numeric increase in mOS of 11.4 months), however, the boundary for significance was not achieved. Also, a favorable OS trend emerged with imlu+abema vs imlu in all pts, regardless of ESR1m. Sustained benefit in PFS, with clinically meaningful improvement in TTC, and PFS2 further highlight the efficacy of imlu-based regimens."

Clinical • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Safety and patient (pt)-reported outcomes (PROs) from evERA breast cancer (BC): A phase III trial of giredestrant (GIRE) + everolimus (E) in pts with oestrogen receptor-positive, HER2-negative advanced BC (ER+, HER2- aBC) previously treated with a CDK4/6 inhibitor (i) (ESMO-BC 2026) - P3 | "We report efficacy/safety PROs and exploratory analyses of stomatitis (an E-associated adverse event [AE]) to further characterise the safety profile of GIRE + E. Pts were randomised 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane/fulvestrant/tamoxifen) + E. Dexamethasone mouthwash (MW; up to four times a day) was strongly recommended for stomatitis prophylaxis. These data further support the manageable safety and tolerability of GIRE + E. Pts with proactive MW prophylaxis had later onset and fewer G ≥ 2 E-associated stomatitis AEs. PROs support tx tolerability, showing maintained QoL, longer TTD in fn, longer time without pain worsening and no increase in tx burden from pts' perspective with GIRE + E."

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

Palbociclib plus exemestane with GnRH agonist vs capecitabine in premenopausal patients with HR+/HER2- metastatic breast cancer: Updated survival results of the randomized phase 2 study Young-PEARL. (ASCO 2024) - P2 | " Premenopausal women aged 19 years or older with HR+/HER2- BC who had relapsed or progressed during previous tamoxifen therapy were enrolled. Young-PEARL study showed exemestane + palbociclib with OFS improves efficacy compared with capecitabine in terms of PFS, which did not lead to an OS benefit for patients with premenopausal HR+/HER2- mBC (median follow-up duration: 54.8 months). The overall safety profile of palbociclib and capecitabine continues to be manageable with longer follow-up."

Clinical • Late-breaking abstract • Metastases • P2 data • Breast Cancer • Dermatology • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

Imlunestrant, an Oral Selective Estrogen Receptor Degrader (SERD), as Monotherapy and Combined with Abemaciclib, for Patients w/ ER+, HER2- Advanced Breast Cancer (ABC), Pretreated w/ Endocrine Therapy (ET): Results of the Phase 3 EMBER-3 trial. (SABCS 2024) - P3 | "Pts were randomized 1:1:1 to imlunestrant (400 mg once daily [QD]), physician’s choice standard-of-care (SOC) ET (fulvestrant or exemestane per label), or imlunestrant (400 mg QD) + abemaciclib (150 mg twice daily). Imlunestrant significantly improved PFS vs SOC in pts with ESR1m, and imlunestrant + abemaciclib significantly improved PFS vs imlunestrant in all pts regardless of ESR1m status. Imlunestrant had a favorable safety profile alone and combined with abemaciclib, thus providing an all-oral targeted therapy option for ET-pretreated pts with ER+, HER2- ABC."

Clinical • Metastases • Monotherapy • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • 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

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

International phase 3 clinical trial evaluating PF-07220060 plus fulvestrant in patients with HR+/HER2− advanced/metastatic breast cancer with progression after a prior CDK4/6 inhibitor. (ASCO 2024) - P3 | "Approximately 500 patients will be randomly assigned (1:1) to receive PF-07220060 (orally and continuously in a 28-day cycle) plus fulvestrant (intramuscular injection on days 1 and 15 of cycle 1 and then on day 1 of each cycle thereafter) or investigator's choice of fulvestrant alone or everolimus plus exemestane, which must be declared before randomization. JCO. 2023; 41:3009."

Clinical • Metastases • P3 data • 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 • BRCA • ER • HER-2 • PIK3CA • PTEN

Suboptimal ovarian suppression during adjuvant endocrine therapy for premenopausal women with breast cancer: An exploratory analysis of the PREFER and GIM 23 studies (ESMO-BC 2024) - P | "Background Adjuvant endocrine therapy (ET) with exemestane combined with LHRH analog (LHRHa) is standard of care for premenopausal women with hormone receptor-positive breast cancer...65.4% of these patients received chemotherapy, mainly anthracycline plus taxane (93.8%), and 3 patients received adjuvant abemaciclib...Monthly leuprorelin was given in 65% of the cases, while the others received monthly triptorelin...Table: 125P Characteristics N of patients (%) TNM - Stage IA 14 (53.9) IB 3 (11.5) IIA 5 (19.2) IIB 2 (7.7) IIIA 2 (7.7) Grading 1 1 (3.8) 2 18 (69.3) 3 5 (19.2) NA 2 (7.7) Histology Ductal 21 (80.8) Lobular 1 (3.8) Other 4 (15.4) Ki67 <20 12 (46.2) ≥20 14 (53.8) HER2 status 0 12 (46.1) 1+ 5 (19.2) 2+ 2 (7.7) 2+ FISH amplified or 3+ 7 (27) Conclusions In our cohort, almost 5% of premenopausal patients did not achieve ovarian suppression with LHRHa. Oncologists should be aware that serial monitoring of estradiol levels should be performed to address this."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Sacituzumab govitecan in ER+/HER2- breast cancer: a necessary treatment option for patients who have undergone multiple prior treatments. (PubMed, Recenti Prog Med) - "Surgery was excluded, so she started CDK4/6 inhibitor and letrozole...Because of further skin and lymph node progression, the patient began everolimus and exemestane in July 2023...The patient started capecitabine and vinorelbine...In March 2025 she began sacituzumab govitecan (SG): after the first month, clinical examination revealed partial remission of subcutaneous nodules and pathological lymph nodes in the right axilla, gradually leading to cuff removal. The possibility to use SG in luminal breast cancer patients gave this woman a chance, in a scenario poor in exciting options."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Randomized Phase II Trial of Endocrine Therapy With or Without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: MAINTAIN Trial. (PubMed, J Clin Oncol) - "In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2- MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET."

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 • HER-2

Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1 results in significant clinical benefit. Additionally, the original design explored in PADA-1 might help with tackling acquired resistance with new drugs in future trials."

Journal • P3 data • Breast Cancer • Cardiovascular • Estrogen Receptor Positive Breast Cancer • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Thrombocytopenia • ER • HER-2

Ovarian function suppression in HR-positive, HER2-positive breast cancer: An exploratory analysis from the HERA trial (ESMO 2024) - P3 | "Clinical trial identification: HERceptin Adjuvant (HERA) (BIG1-01; NCT00045032)...We also assessed the prognosis based on the type of antihormone therapy (tamoxifen or aromatase inhibitor) used with OFS. The analysis included 965 patients, of which 501 (51.9%) received only tamoxifen and 464 (48.1%) received antihormonal therapy with OFS (tamoxifen [n = 269, 27.9%] or exemestane [n = 195, 20.2%])... Our results support the addition of OFS to antihormonal therapy as a reasonable strategy in premenopausal women with HR-positive, HER2-positive breast cancer who are undergoing chemotherapy and HER2-targeted therapy. While the aromatase inhibitor appears to be more beneficial than tamoxifen when paired with OFS, further research is needed to determine the most effective antihormonal therapy to combine with OFS in this specific patient population."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Prognostic value of HER2-low status in metastatic breast cancer (mbc) patients treated with I line CDK 4/6 inhibitors (CDK 4/6i): A real-word analysis of the GIM14/BIOMETA study (ESMO-BC 2024) - P | "Among those who experienced disease progression, after CDK 4/6i 40% of patients received chemotherapy (more frequently capecitabine or taxane plus bevacizumab), 36% endocrine treatment (the majority exemestane+ everolimus or fulvestrant), 2% PARP inhibitors or alpelisib, and 9% CDK 4/6i beyond progression. In 13% of cases II line data were not reported. Conclusions No significant difference in terms of survival outcomes were found between patients affected by HER2-zero and HER2-low breast cancer treated in I line with CDK 4/6i."

Clinical • Metastases • 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 • CDK4 • HER-2

Post-progression treatment (tx) analyses of evERA Breast Cancer (BC): A phase III trial of giredestrant (GIRE) + everolimus (E) in patients (pts) with estrogen receptor–positive, HER2-negative advanced BC (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i). (ASCO 2026) - P3 | " Pts with ER+, HER2– aBC who had disease progression (PD) or relapse during/post-CDK4/6i + ET were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane/ fulvestrant/tamoxifen) + E until PD/unacceptable toxicity. Delaying chemotherapy improves clinical and quality of life outcomes in ER+ aBC. These analyses further support the superior INV-PFS of GIRE + E over SOC ET + E observed in all pts and in the ESR1m population. Improvements in PFS2 and CFS, regardless of ESR1m status, suggest that the clinical benefit of GIRE + E is sustained beyond initial progression."

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

Palbociclib plus endocrine therapy versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (Young-PEARL): overall survival analysis of a randomised, open-label, phase 2 study. (PubMed, Lancet Oncol) - P2 | "With extended follow-up, palbociclib plus exemestane with ovarian function suppression continued to show a significant benefit in progression-free survival compared with capecitabine in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had been previously treated with tamoxifen; however, no improvement in overall survival was seen. Given the progression-free survival benefit, the upfront use of palbociclib plus endocrine therapy is the preferred option for premenopausal women, although a capecitabine-first strategy might be an alternative treatment strategy for maintaining overall survival in resource-limited settings."

Journal • P2 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

Safety Extension Study for Subjects With HR+, HER2- Breast Cancer for Subjects Who Have Completed the OVELIA Study (clinicaltrials.gov) - P3 | N=250 | Enrolling by invitation | Sponsor: Tolmar Inc. | Trial completion date: Jun 2028 ➔ Mar 2030 | Trial primary completion date: Jun 2028 ➔ Mar 2030

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Circulating Tumour DNA (ctDNA) Dynamics From Patients With ER+, HER2- Advanced Breast Cancer in the Phase 3 EMBER-3 Trial (SABCS 2025) - "Background: The EMBER-3 trial, which included patients with ER+/HER2- advanced breast cancer previously treated with endocrine therapy (ET), demonstrated a significant improvement in progression-free survival (PFS) with imlunestrant (imlu) over standard ET (SOC ET, fulvestrant or exemestane) in patients with ESR1 mutations (ESR1m). Analyses of early ctDNA dynamics from EMBER-3 demonstrated greater early ctDNA reduction with imlunestrant compared with SOC ET in patients with ESR1m. The addition of abemaciclib to imlunestrant enhanced ctDNA decline in all patients, consistent with the primary study outcomes. Furthermore, while a ≥50% decline in ctDNA at C2D21 was associated with improved PFS, the allocated treatment remained a key determinant of patient outcomes."

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

EVERolimus effectiveness after proGREssion on CDK4/6 inhibitors for ENdocrine receptor-positive/HER2-negative, advanced breast cancer: EVERGREEN quasi-experimental study (ESMO 2024) - P2, P3, P4 | "We excluded pts receiving alpelisib as immediate next line...ET was mostly exemestane in EVE-cohort (77%) and fulvestrant in ETa-cohort (61%)... We found a non-statistically significant trend for superiority of EVE compared to ETa for unadjusted rwPFS. Pts with PIK3CA-AKT-PTEN pathway alterations, may particularly benefit from the combination."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study. (PubMed, Eur J Cancer) - P3 | "Palbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors."

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

Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial (ESMO 2025) - P3 | "Randomisation was 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane/fulvestrant/tamoxifen) + E until PD or unacceptable toxicity. The safety profile of GIRE + E was manageable with no unexpected findings. GIRE + E may represent a new effective treatment option in the post-CDK4/6i setting."

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

Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor (SABCS 2025) - P3 | "Methods Pts who had ER+, HER2- aBC with disease progression (PD) post-CDK4/6i + ET in the aBC setting, or relapse during/after CDK4/6i + ET in the adjuvant setting, were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane, fulvestrant, or tamoxifen) + E until PD or unacceptable toxicity. Conclusions GIRE + E led to clinically meaningful improvements in INV-PFS vs SOC ET + E irrespective of PIK3CAm and PIK3CA/AKT1/PTEN alt, and other key relevant subgroups, regardless of ESR1m status. These data support the use of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET."

Biomarker • Clinical • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN

Dalpiciclib Combined With Aromatase Inhibitors and Olmesartan as the First-line Treatment for HR+/HER2- Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Patient-reported outcomes (PROs) in patients with ER+, HER2- advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant + abemaciclib: Results from the phase III EMBER-3 trial. (ASCO 2025) - P3 | "The EMBER-3 trial, in patients (pts) with ER+, HER2- ABC who had disease progression on or after aromatase inhibitor-based therapy, showed significant progression free survival (PFS) improvement with imlu vs standard therapy (SOC, fulvestrant or exemestane) in pts with ESR1 mutations (ESR1m), and with imlunestrant+abemaciclib (imlu+abema) vs imlu in all pts, regardless of ESR1m. PROs from EMBER-3 demonstrated that patients with ESR1m had better GHS/QOL and PF with imlu vs SOC, mirroring efficacy results. While the frequency of CTCAE defined ISRs was low, the high rate of PRO-CTCAE ISR demonstrates that this clinically relevant adverse event is underappreciated by physicians. Additionally, all pts had generally comparable GHS/QOL and PF with imlu+abema vs imlu."

Clinical • Metastases • P3 data • Patient reported outcomes • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • ER • HER-2

Efficacy and safety of dalpiciclib, exemestane, and goserelin as neoadjuvant therapy in premenopausal HR-positive, HER2-negative breast cancer patients: A phase II clinical trial (ESMO 2024) - P2/3 | "Participants initially received two cycles of TAC (docetaxel, doxorubicin, and cyclophosphamide). Preliminary results advocate for the use of dalpiciclib, exemestane, and goserelin as an effective alternative to continued chemotherapy in premenopausal HR-positive, HER2-negative BC patients unresponsive to initial neoadjuvant chemotherapy. This strategy offers notable treatment benefits, diminishes adverse events, and enhances patient quality of life. Further enrollment up to 43 participants will continue based on these findings."

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

POLAR: Palbociclib for HR Positive / HER2-negative Isolated Locoregional Recurrence of Breast Cancer (clinicaltrials.gov) - P3 | N=405 | Active, not recruiting | Sponsor: ETOP IBCSG Partners Foundation | Trial primary completion date: Jul 2026 ➔ Dec 2026

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