Kisqali (ribociclib) / Otsuka, Novartis - LARVOL DELTA

Phase II Trial of Ribociclib Plus Letrozole in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube, or Peritoneum: A GOG Partners Trial (GOG 3026). (PubMed, J Clin Oncol) - "Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype."

Journal • P2 data • Breast Cancer • Fallopian Tube Cancer • Hematological Disorders • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Low Grade Serous Carcinoma • Neutropenia • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • ER

Risk of venous thromboembolism associated with CDK 4/6 inhibitors and adjuvant hormonal therapy in non-metastatic breast cancer: A systematic review and meta-analysis (ASH 2025) - "More recently, the Introduction of cyclin-dependentkinase 4 and 6 (CDK 4/6) inhibitors, Abemaciclib, Palbociclib, and Ribociclib, has led to new treatment forhigh-risk patients...The comparator group in thisanalysis consisted of patients treated with endocrine therapy alone with aromatase inhibitors (AI),tamoxifen, or fulvestrant... Results from this study show that for adult patients with local and locally advanced breastcancer, there is increased risk of VTE development when treated with CDK 4/6 inhibitors compared totreatment with endocrine therapy alone. Limitations to this analysis include exclusion of metastaticdisease, limited data available on mortality associated with VTE incidence, and varying degrees of patient-specific thromboembolic risk factors. As the use of CDK 4/6 inhibitors in the treatment of breast cancergrows, this information will provide further information for conversations about risks and benefits whenselecting treatment plans."

Metastases • Retrospective data • Review • Breast Cancer • Chronic Kidney Disease • Genetic Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Respiratory Diseases • Solid Tumor • Venous Thromboembolism • HER-2

BI14 Case series: exploring the link between psoriasis and cyclin-dependent kinase 4/6 inhibitors in breast cancer treatment. (PubMed, Br J Dermatol) - "She was initiated on palbociclib and letrozole treatment in April 2024...She was commenced on ribociclib and letrozole for relapsed metastatic liver disease in April 2023...Understanding the role of CDK4/6 inhibition and the link with psoriasis is important for optimizing therapeutic choices for patients with cancer with pre-existing or newly developed psoriasis. Given the increasing use of CDK4/6 inhibitors in cancer treatment, clinicians should be vigilant of the potential increased prevalence of psoriasis experienced in this patient cohort."

Journal • Breast Cancer • Dermatology • Dermatopathology • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Oncology • Psoriasis • Solid Tumor • ER • HER-2 • IL17A • IL22

Analysis of Asian patients (pts) with HR+/HER2− early breast cancer (EBC) treated with ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI): 5-year outcomes from NATALEE (ESMO Asia 2025) - P3 | "Consistent with prior analyses, this subgroup analysis of NATALEE shows a clinically meaningful efficacy benefit of adding RIB to NSAI with manageable safety and maintained QoL in Asian pts with stage II/III HR+/HER2− EBC. Table: LBA1 HR, hazard ratio; DDFS, distant disease-free survival; DRFS, distant recurrence-free survival; iDFS, invasive disease-free survival; RFS, recurrence-free survival."

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

Efficacy of ribociclib plus fulvestrant in patients with hormone receptor-positive, HER2-negative recurrent or metastatic breast cancer at Vietnam National Cancer Hospital (ESMO Asia 2025) - "Treatment with Ribociclib in combination with Fulvestrant in patients with hormone receptor-positive and HER2-negative recurrent or metastatic breast cancer is a safe and effective regimen, especially in first-line therapy. This regimen should be widely used in clinical practice."

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 • HER-2

Molecular classification of breast cancer in Bhutan (ESMO Asia 2025) - "This analysis highlights the molecular heterogeneity of breast cancer in Bhutan, with a significant proportion of HER2+ and TNBC cases. The high rate of advanced-stage presentation underscores the need for earlier detection. The high mastectomy rate reflects the absence of radiotherapy in-country."

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

Cyclic kinase 4 and 6 inhibitor plus endocrine therapy (ET) as first-line therapies in advanced breast cancer: A patient-level data network meta-analysis (ESMO Asia 2025) - "In the first-line setting for HR+/HER2− advanced breast cancer, all CDK4/6 inhibitors combined with endocrine therapy significantly improve progression-free survival compared with endocrine therapy alone, with no significant differences observed among them."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Effectiveness and safety of ribociclib versus abemaciclib in the management of HR-positive and HER2-negative metastatic breast cancer: A multi-center retrospective cohort in Saudi Arabia (ESMO Asia 2025) - "Patients with a history of prior use of CDK 4/6 inhibitors or concomitant use of Tamoxifen with Ribociclib were excluded. Of 318 screened patients, 142 met the inclusion criteria. This study concludes that Abemaciclib and Ribociclib demonstrate comparable PFS, with safety profiles consistent with those reported from MONALEESA and MONARCH trials. Notably, hyperkalemia was identified as a potential adverse event not previously reported in the literature."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Genomic testing and survival outcomes in metastatic breast cancer: A retrospective study from western India (ESMO Asia 2025) - "Among HR+ patients, 64.2% (318/495) received hormonal therapy, including Palbociclib/Ribociclib in n=115 cases; 62.8% (183/292) of HER2+ patients received targeted therapy. Enhancing access to genomic testing and targeted therapies, along with strengthening real-world data and integrating precision oncology into routine practice, are crucial for optimizing outcomes in metastatic breast cancer."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • FGFR2 • HER-2 • TP53

Efficacy of abemaciclib following progression on prior CDK4/6i in HR+/HER2- metastatic breast cancer: Real-world experience in Moscow (ESMO Asia 2025) - "Of these, 23 patients had previously progressed on first line palbociclib (n=12) or ribociclib (n=11) and were subsequently treated with abemaciclib plus fulvestrant. Median age was 62 years (range: 31–88). Our real-world data support the use of abemaciclib after progression on other CDK4/6i. The observed clinical benefit is consistent with previously published data from the postMONARCH study and other retrospective series. Sequential use of CDK4/6i may be a valuable treatment strategy for selected patients with sustained endocrine sensitivity, delaying the need for chemotherapy."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Results of repeat core needle biopsies in ER+/HER2-negative breast cancer following neoadjuvant endocrine therapy with fulvestrant+triptorelin+ribociclib in premenopausal women (ESMO Asia 2025) - "The fulvestrant+triptorelin+ribociclib combination (NET) induced rapid reduction in proliferative activity (Ki-67), modulation of hormone receptor expression. Observed changes may reflect the tumor heterogeneity or pharmacodynamic treatment effects. The clinical significance of marker dynamics requires long-term follow-up to assess prognostic value."

Biopsy • Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Safety of CDK4/6 inhibitors in older patients: A FAERS-based analysis of serious and fatal adverse events. (PubMed, J Geriatr Oncol) - "Real-world data reveal drug- and age-specific toxicity differences. Ribociclib and abemaciclib pose higher risks in older adults compared to palbociclib, supporting the need for personalized treatment and careful monitoring in older patients."

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

The potential effects of the synergistic interaction between ferulic acid and new generation CDK inhibitor anti-neoplastic drugs on breast cancer anti-tumour activity. (PubMed, Med Oncol) - "Ribociclib (Ribo) and Abemaciclib (Abe) are new-generation CDK inhibitors approved for use in breast cancer treatment. Some molecular mechanisms were elucidated by revealing the synergistic effect of FA combined with Ribo and/or Abe in both HR positive and HR negative breast cancer and its possible toxicity or protection on normal breast cells. The present findings suggest that FA is a viable candidate for adjuvant or neoadjuvant treatment in combination with Ribo and/or Abe, as an alternative to Letrozole or Fulvestrant, which have been associated with significant adverse effects in clinical settings."

Journal • Breast Cancer • Eye Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • ER

A randomized phase II study to evaluate the efficacy and safety of Trastuzumab deruxtecan (T-DXd) versus CDK4/6 inhibitor-based endocrine therapy as first-line therapy of hormone receptor-positive (HR+) and HER2-low/ultralow advanced breast cancer (ABC) patients classified as non-luminal subtype according to gene expression profiling: the PONTIAC study (SABCS 2025) - P2 | "Moreover, pts treated with a CDK4/6 inhibitor in the adjuvant setting with a treatment-free interval ≥ 12 months following CDK4/6 inhibitor treatment completion are allowed.Pre-screening central PAM50 analysis will be conducted in endocrine-resistant pts and in endocrine-sensitive pts who meet at least one of the following criteria: estrogen receptor expression ≤ 50% or presence of liver metastases, or high histological grade or Ki67 > 50% in the primary tumor or known non-luminal subtype as per local PAM50 analysis.Pts will be randomized 1:1 to either T-DXd (5.4 mg/kg intravenously once every 3 weeks) or endocrine therapy (fulvestrant or an aromatase inhibitor ± GnRH analogs for men and pre-/perimenopausal women) plus investigator's choice of CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib). Pts-reported outcomes and safety will be analyzed descriptively. Target enrollment is 200 pts, and initial patient enrollment is anticipated to begin in..."

Clinical • Gene expression profiling • Metastases • P2 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 • ER • HER-2

Retrospective study evaluating eligibility, treatment patterns, and clinicopathologic factors associated with adjuvant abemaciclib use in patients with high-risk estrogen receptor-positive (ER+) HER2-negative (HER2-) early breast cancer (EBC) (SABCS 2025) - "13 (25.5%) pts were offered but declined abema, 4 (7.8%) were lost to follow-up, 3 (5.9%) started ribociclib. Other reasons: comorbidity+age (n=4, 7.8%), ≥3 comorbidities (n=1, 2%), severe comorbidity (n=2, 3.9% [Crohn's disease and psychiatric disorder]), poor ET tolerance (n=2, 3.9%), ongoing olaparib (n=1, 2%), metastatic disease at post-surgical staging (n=1, 2%), pt hesitation despite abema prescription (n=2, 3.9%)... In this cohort, a gap between EAT and ENT pts was seen. Older age and lower nodal burden were associated with not receiving adj abema. Pt choice and comorbidities also contributed to non-initiation."

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

Randomized open-label multicenter phase 2 trial comparing first-line olaparib versus CDK4/6 inhibitor plus endocrine therapy in patients with gBRCAmut-associated HR+/HER2- advanced breast cancer [BR21-08, OPERA trial] (SABCS 2025) - "Six patients received CDK4/6i+ET (2 ribociclib, 2 abemaciclib, 2 palbociclib) and 3 received olaparib as first-line therapy. In gBRCAmut HR+/HER2- ABC, first-line olaparib demonstrated numerically longer PFS and a favorable safety profile compared with CDK4/6i plus ET. These findings should be interpreted with caution given the small sample size."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • HER-2 • HRD

Liquid Biopsy-Based Molecular Profiling Using Guardant360 CDx at Progression on CDK4/6i+ET: Findings from the AGO-B CAPTOR Study (SABCS 2025) - P4 | "The AGO-B "Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients" (CAPTOR) trial (NCT05452213) is a single-arm, open-label phase IV study of patients with advanced HR+/HER2- breast cancer who were treated with ribociclib and endocrine therapy...Twelve (39%) had an indication for Alpelisib due to an activating mutation in PIK3CA, nine (29%) an indication for Elacestrant based on an activating mutation in ESR1, sixteen (52%) an indication for Capivasertib due to PIK3CA, AKT1 or PTEN mutation and one patient (3%) had a ERBB2 amplification resulting in an indication for an anti-HER2 treatment...Of those, seven (41%) received treatment in accordance with ctDNA test result (29% Capivasertib, 6% Trastuzumab, 6% Elacestrant). Guardant360 CDx testing was initiated for 37 patients between December 2024 and June 2025. Of those, two were cancelled due to shipment delays and four..."

Biopsy • Liquid biopsy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • AKT1 • BRCA1 • BRCA2 • CDK4 • ER • PIK3CA • PTEN

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

Updated results and an exploratory analysis of ESR1m circulating tumor DNA (ctDNA) dynamics from SERENA-6, a phase 3 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1 mutations (ESR1m) during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (SABCS 2025) - "Methods SERENA-6, a randomized, double-blind, phase 3 trial, enrolled pts with HR+/HER2- ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (palbociclib/ribociclib/abemaciclib). No new safety signals were observed. These results further support an early switch to CAMI + CDK4/6i during 1L therapy to delay disease progression."

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

At-home complete blood count monitoring: enhancing care pathways and improving patient experience (SABCS 2025) - "Questionnaires asked participants their preference for self-testing compared to standard testing and to rate on a scale of 1-5, their experience of training, self-testing, acceptability of testing cadence, sense of control, perceived time savings, overall patient experience, likelihood to recommend Liberty to other patients and any additional comments. Patients receiving a range of SACT (paclitaxel, ribociclib, abemaciclib, trastuzumab deruxtecan, sacituzumab govitecan) were recruited over 9 months to this sub-study (n=10). Liberty was the preferred pathway for blood monitoring and may help to reduce the significant burden faced by patients and healthcare systems for cancer treatment. Subsequent real-world usage of Liberty has demonstrated reductions of up to 91% of routine in-clinic blood tests and shown its utility in avoiding unnecessary emergency room attendance."

Clinical • Breast Cancer

Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=792 | Recruiting | Sponsor: Hoffmann-La Roche | N=580 ➔ 792 | Trial completion date: May 2028 ➔ Sep 2030 | Trial primary completion date: May 2028 ➔ Sep 2030

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • PIK3CA

Implications of PIK3CA/HER2 Status and Age/Comorbidities on Clinical Investigators' (CIs) Selection of First-Line Systemic Therapy for Hormone Receptor-Positive (HR+) Metastatic Breast Cancer (mBC) (SABCS 2025) - "A modest honorarium was offered. Ribociclib (R) was the most common CDKi recommended for PIK3CA-wildtype, HER2-negative tumors, including patients with symptomatic visceral and asymptomatic bone metastases (Table). For patients with PIK3CA-mutated tumors with disease relapse 2 years into adjuvant endocrine therapy (ET), respondents most commonly recommended inavolisib (I)/palbociclib (P)/ET, and of great interest, 7 of 20 CIs would recommend this triplet for a patient with de novo disease. For patients with HR+, HER2-positive tumors, P/ET in addition to trastuzumab/pertuzumab was the most common recommendation for postchemotherapy/anti-HER2 maintenance treatment... The clinical practice trend of selecting R as the preferred initial CDKi because of its consistent overall survival benefit has been modified by data from INAVO120 and PATINA, in which the perceived better tolerability of P led to its combination with targeted therapies that significantly improved outcomes...."

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 • HER-2 • PIK3CA

Mechanisms of resistance to capivasertib in combination with CDK4/6 inhibitor (CDK4/6i) plus fulvestrant in patients with hormone receptor-positive/HER2-negative (HR+/HER2−) advanced breast cancer (ABC): exploratory analysis from the Phase 1b CAPItello-292 study (SABCS 2025) - P3 | "Results from Phase 1b of the CAPItello-292 Phase 1b/3 trial (NCT04862663) have shown that triplet therapy with pan-AKT inhibitor capivasertib + CDK4/6i (palbociclib or ribociclib) + fulvestrant is tolerable in patients with HR+/HER2− ABC, with preliminary evidence of clinical activity. Conclusions Consistent with AKT being a pivotal node in the PI3K/AKT signaling pathway, these data show that treatment with capivasertib + fulvestrant + CDK4/6i resulted in emergence of alterations associated with activation of alternate mechanisms, such as mTORC1, RAS, and AMPK. The CRISPR data provides additional support to clinical observations."

Clinical • Combination therapy • Metastases • P1 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 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN • RICTOR • STK11 • TSC1 • TSC2

Emulation of the MONALEESA-2 Trial Using Specialty Oncology Electronic Health Records Databases (clinicaltrials.gov) - P=N/A | N=2495 | Active, not recruiting | Sponsor: Shirley Vichy Wang

New trial • Breast Cancer • Oncology • Solid Tumor

Retrospective review of metastatic hormone receptor-positive inflammatory breast cancer patients reveals poor responses to cyclin dependent kinase 4/6 inhibition. (PubMed, Breast Cancer Res) - "Patients with metastatic HR+HER2- IBC demonstrated a shorter time on treatment suggesting shorter duration of response on CDKI + HT, which is markedly inferior to reported data for non-IBC patients from phase III trials."

Journal • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • ARID1A • CCND1 • ER • FGFR1 • HER-2 • PIK3CA • TP53