Ibrance (palbociclib) / Pfizer, Amgen - LARVOL DELTA

VIKTORIA-1: Updated results of a randomized, open-label, phase 3 study of gedatolisib (geda) + fulvestrant (fulv) ± palbociclib (palbo) vs standard of care in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (Study 2) (ESMO 2026) - No abstract available

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

WHEN TARGETED THERAPY MEETS THE LIVER: SEVERE HEPATOTOXICITY INDUCED BY RIBOCICLIB–LETROZOLE (UEGW 2026) - "Notably, endocrine therapy was subsequently reintroduced with tamoxifen in combination with palbociclib, which was well tolerated, with no recurrence of hepatotoxicity.This case highlights that ribociclib–letrozole can induce severe hepatotoxicity, requiring prompt recognition and drug discontinuation. The absence of recurrent liver injury with palbociclib suggests a drug-specific rather than a class effect, supporting the possibility of a safe therapeutic alternative within the same class."

Breast Cancer • Cholestasis • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Liver Failure • Solid Tumor • HER-2

Genetic Variation in NR1I2 and Palbociclib Safety and Prognosis in Advanced Breast Cancer: An Exploratory Multicenter Study. (PubMed, Int J Mol Sci) - "The findings of this exploratory study suggest potential associations between the NR1I2 rs6785049 variant and treatment toxicity and survival outcomes in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer treated with palbociclib. However, these hypothesis-generating findings need to be independently validated."

Clinical • Journal • 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 • ABCB1 • ABCG2 • CDKN1B • CYP3A4 • HER-2 • NR1I2

Translational pharmacokinetic/pharmacodynamic modeling to inform target concentration and dose projection of a novel selective estrogen receptor degrader (SIM0270) for early clinical development. (PubMed, J Pharmacol Exp Ther) - "Combination with palbociclib further enhanced tumor reduction by 42.7%. Model-based simulations identify target concentrations for tumor stasis and maximal suppression, informing rational clinical dose selection. The iterative framework integrates nonclinical priors and adapts to emerging clinical data, improving decision-making across drug development."

Journal • PK/PD data • Oncology • ER • PGR

Non-invading cells that coordinate with tip cells during angiogenic sprout initiation exhibit a molecular signature driven by YAP and TAZ. (PubMed, Am J Physiol Cell Physiol) - "Altogether, this study reveals that YAP and TAZ localize more frequently to the nucleus in non-invading cells but remain more cytoplasmic in tip cells, consistent with a proliferative phenotype in non-tip cells. These results provide insights into how endothelial plasticity is regulated during angiogenic sprout initiation in 3D."

Journal • TAFAZZIN

NeoPalAna: PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer (clinicaltrials.gov) - P2 | N=84 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Aug 2026 ➔ Nov 2027

Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Patient-reported health-related quality of life (HRQoL) with extended palbociclib use (≥3 years) in HR+/HER2− metastatic breast cancer (mBC), interim analysis (IA) from a global non-interventional study (NIS) (ESMO 2026) - No abstract available

Clinical • HEOR • Metastases • Observational data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ctDNA and Thymidine Kinase Activity Identify High-Risk Disease and Resistance Evolution in HR+/HER2− Metastatic Breast Cancer: Data from the Fulvestrant±Palbociclib Randomized Phase II FLIPPER Trial (ESMO 2026) - No abstract available

Circulating tumor DNA • Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PXR rs6785049 as a pharmacogenetic marker for treatment personalization with palbociclib in advanced breast cancer: a multicenter study (ESMO 2026) - No abstract available

Biomarker • Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor

Comparison of overall survival (OS) and progression-free survival (PFS) of palbociclib versus ribociclib in patients with HR+/HER2- metastatic breast cancer (mBC): A real-world SONABRE study (ESMO 2026) - No abstract available

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 • HER-2

A Global, Interventional, Open-Label Trial of Trastuzumab Deruxtecan (T-DXd)–Based Therapy Followed by Palbociclib, Endocrine Therapy (ET), and Dual HER2 Blockade in First-Line (1L) Human Epidermal Growth Factor Receptor 2–Positive (HER2+), Hormone Receptor–Positive (HR+) Advanced or Metastatic Breast Cancer (mBC) and Retreatment With T-DXd (DESTINY-Breast Guide) (ESMO 2026) - No abstract available

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

A Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Gedatolisib with Endocrine Therapy (ET) and Palbociclib vs ET and Ribociclib as First-Line (1L) Treatment in Patients With HR-Positive (HR+) HER2-Negative (HER2-) Advanced Breast Cancer (ABC) (VIKTORIA-2) (ESMO 2026) - No abstract available

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 • HER-2

Final long-term outcomes of palbociclib-fulvestrant vs. placebo-fulvestrant in HR+/HER2‒ endocrine-sensitive advanced breast cancer: GEICAM/2014-12 (FLIPPER) phase II trial (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Long-term real-world overall survival with first-line palbociclib + aromatase inhibitor (AI) vs AI alone in HR+/HER2− metastatic breast cancer: a 10-year retrospective US study (ESMO 2026) - No abstract available

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

ImmunoADAPT: Neoadjuvant Endocrine Therapy, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2026 ➔ Mar 2027 | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • ER

First-line CDK4/6 inhibitor treatment of HR-positive, HER2-negative metastatic breast cancer: real-world data from Ho Chi Minh City Oncology Hospital, Vietnam. (PubMed, Front Oncol) - "We conducted a retrospective cohort study enrolling 107 patients who received first-line ribociclib or palbociclib in combination with an aromatase inhibitor or fulvestrant at Ho Chi Minh City Oncology Hospital between March 1, 2021, and April 1, 2023. Treatment outcomes and safety profiles were consistent with those reported in pivotal clinical trials and real-world studies. These findings should be interpreted in light of the retrospective single-center design, modest sample size, non-randomized treatment allocation, and immature OS data."

Journal • Real-world evidence • Breast Cancer • Febrile Neutropenia • 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

Treatment Patterns and Clinical Outcomes Among Patients Receiving Palbociclib Combinations for Hormone Receptor-Positive (HR+)/Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Advanced/Metastatic Breast Cancer in the Arabian Gulf Region: A Retrospective Study (TREASURE Study). (PubMed, Int J Breast Cancer) - P | "Treatment regimens included palbociclib plus aromatase inhibitors (n = 142, 55.0%) and palbociclib with fulvestrant (n = 120, 46.5%). Larger studies with more patients are needed to further assess long-term clinical outcomes in this population. Trial Registration: ClinicalTrials.gov identifier: NCT04916509."

Clinical • Clinical data • 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 • Oncology • Solid Tumor • HER-2

Risk-Window Palbociclib Exposure Delays ErbB2-Driven Mammary Tumorigenesis and Suppresses Mammary Epithelial Cell Stemness. (PubMed, bioRxiv) - "Mechanistically, palbociclib-treated tissues showed inhibition of the Cyclin D1-CDK4/6-RB-E2F axis and coordinated attenuation of ER-, ErbB2- and Wnt/β-catenin-associated signaling. Together, we demonstrate that short-term CDK4/6 inhibition during a premalignant risk window produces a sustained delay in ErbB2-driven mammary tumorigenesis, associated with remodeling of the mammary epithelial hierarchy and suppression of proliferative and stem/progenitor-associated activity, suggesting CDK4/6 inhibition as a strategy for ErbB2-positive BC prevention."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CCND1 • CD24 • HER-2 • ITGA6 • ITGB3

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

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

Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study. (PubMed, Lancet Oncol) - P2 | "Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen."

Journal • P2a data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1/L1 Inhibitor (clinicaltrials.gov) - P3 | N=81 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Feb 2028 ➔ Feb 2029 | Trial primary completion date: Feb 2028 ➔ Feb 2029

Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A

Neoadjuvant nivolumab (NIVO) + palbociclib (PALBO) + anastrozole (ANA) for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2_) primary breast cancer (BC): CheckMate 7A8 (ESMO-BC 2022) - P2 | "Neoadjuvant NIVO + PALBO + ANA showed a higher incidence of grade ≥3 hepatic TRAEs than historical single-agent safety profiles. These findings show a potential safety risk for the use of endocrine therapy with PD-1 + CDK 4/6 blockade."

Clinical • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2

LINC01871-Mediated Sensitivity to Cyclin-Dependent Kinase 4/6 Inhibitors in Human Breast Cancer. (PubMed, J Vis Exp) - "Sixty-two lncRNAs associated with predicted sensitivity to ribociclib and palbociclib were identified, and six core lncRNAs were selected. These findings identify LINC01871 as a candidate biomarker of sensitivity to CDK4/6 inhibitors and demonstrate its tumor-suppressive effects in breast cancer. Further clinical and mechanistic studies are required to validate its predictive value and therapeutic relevance."

Journal • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • LINC01871

PARSIFAL-LONG: Extended follow-up of hormone receptor-positive /HER2-negative advanced breast cancer patients treated with fulvestrant and palbociclib vs. letrozole and palbociclib in the PARSIFAL study (SABCS 2023) - "Extended follow-up analysis from PARSIFAL study confirms no major differences between LET or FUL when combined with PAL. mPFS and mOS results are consistent with those reported in other first-line trials involving different CDK4/6i. Progression within the first year of first-line CDK4/6i-based regimen for HR+/HER2- ABC pts may be prognostic of less favorable outcomes."

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