Ibrance (palbociclib) / Pfizer, Amgen - LARVOL DELTA

Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. (ASCO 2025) - P3 | " Pts with HR+/HER2– ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (abemaciclib/palbociclib/ribociclib) were enrolled and had ctDNA tested for ESR1m every 2–3 months, coinciding with routine imaging. Camizestrant + CDK4/6i guided by emergence of ESR1m during 1L AI + CDK4/6i in pts with HR+/HER2– ABC resulted in a statistically significant and clinically meaningful improvement in PFS. SERENA-6 is the first global Phase 3 trial to demonstrate clinical utility of using ctDNA to detect and treat emerging resistance, ahead of disease progression. These findings represent a potential new treatment strategy to optimize and improve 1L patient outcomes."

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

First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. (PubMed, N Engl J Med) - P3 | "In patients with ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.)."

Journal • 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

Palbociclib and trastuzumab for HER2-positive metastatic breast cancer: final overall survival results of cohort A and B of SOLTI-1303-PATRICIA trial. (PubMed, ESMO Open) - P2 | "These findings highlight the relevance of gene expression profiling in HER2-positive breast cancer and support biomarker-driven patient selection. Long-term PATRICIA results validate the potential of non-chemotherapy-based approaches in HR-positive/HER2-positive MBC."

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

Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1 (ESMO 2025) - "Hyperglycemia incidence was 9.2% and 11.5%, respectively, with grade 3 severity in 2.3% of pts in both geda groups. Conclusions These data support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of pts with HR+/HER2-/PIK3CA WT ABC."

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

Central Nervous System Outcomes from the Phase III PATINA Trial (AFT-38) (SABCS 2025) - "These findings suggest that palbociclib may help delay or prevent CNS involvement in HR+/HER2+ MBC, warranting confirmation in future studies.Table 1. Cumulative Incidence of CNS Progression or Death Among Patients Without CNS Metastases at Baseline"

P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer

Tumor-informed circulating tumor DNA analysis to assess molecular residual disease for prognosis and prediction of benefit from palbociclib in the PALLAS trial (SABCS 2025) - P3 | "Results for association of MRD status (positive/negative) and MTM/mL with DRFI in the context of 7 year median follow up of this study cohort will be reported.Conclusions. The planned analysis is ongoing and the presented work will provide data from the first randomized phase 3 adjuvant study in HR+/HER2- breast cancer to report MRD status by treatment arm."

Biomarker • Circulating tumor DNA • Residual disease • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • HER-2

Gedatolisib, a multi-target PI3K/AKT/mTOR (PAM) inhibitor, plus fulvestrant with or without palbociclib for second-line (2L) treatment of patients with HR+/HER2-/PIK3CA-wild type (WT) advanced breast cancer (ABC): updated results from the randomized, phase 3 VIKTORIA-1 trial (SABCS 2025) - "In preclinical studies, gedatolisib demonstrated superior potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus, regardless of PI3K-pathway mutation status, and combinations of gedatolisib + fulvestrant, with and without palbociclib, were active in treatment-naive and resistant cell lines. These updated results support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of patients with HR+/HER2-/PIK3CA WT ABC."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Efficacy of maintenance endocrine therapy combined with trastuzumab + pertuzumab following taxane induction in HR+/HER2+ metastatic breast cancer: A real-world reproduction of the PATINA trial control arm. (SABCS 2025) - "Background: The PATINA trial demonstrated that adding the CDK4/6 inhibitor palbociclib to maintenance endocrine therapy (ET) and trastuzumab ± pertuzumab significantly prolonged median progression-free survival (PFS) by approximately 15 months (HR 0.74 [95% CI: 0.58-0.94]). In this real-world analysis, patients with HR+/HER2+ MBC treated with first-line metastatic induction chemotherapy followed by maintenance trastuzumab + pertuzumab and ET achieved outcomes in line with those reported in the control arm of the PATINA trial."

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

Effectiveness comparison of first-line CDK4/6 inhibitors in patients with hormone-positive HER2-negative advanced breast cancer according to tumor histology: a sub-analysis of the real-world, multicenter, Italian study PALMARES-2. (PubMed, Breast) - P | "Tumor histology affects the real-world effectiveness of first line ET plus CDK4/6i. In ILC, all three CDK4/6i performed similarly; therefore, treatment selection should prioritize tolerability, manageability, drug-drug interactions, and patient preferences."

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

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=1376 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2026 ➔ Jan 2027

Biomarker • Trial completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Ewing Sarcoma • Germ Cell Tumors • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Langerhans Cell Histiocytosis • Lymphoma • Medulloblastoma • Nephrology • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Pediatrics • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • BRAF

Continuous Flow Paper Spray Ionization Mass Spectrometry for In-Depth Characterization of Anticancer Drugs in Tissues: Addressing Mass Spectral Complexity. (PubMed, J Am Soc Mass Spectrom) - "Using patient-derived xenograft (PDX) mouse model tissue samples, we observed differential absorption of three anticancer drugs, palbociclib, copanlisib, and olaparib. Tandem mass spectrometric analysis explored the in-source chemical reactivity of these drugs, leading to significant spectral complexity. Our findings highlight the importance of careful spectral interpretation in complex biological matrices and support the development of future rapid quantitative CFPSI analysis of these drugs in tissue samples."

Journal • Oncology

Gedatolisib Combined with Palbociclib and Letrozole in Patients with No Prior Systemic Therapy for Hormone Receptor Positive, HER2 Negative Advanced Breast Cancer. (PubMed, Clin Cancer Res) - "Gedatolisib plus palbociclib and letrozole demonstrated preliminary efficacy in patients with no prior systemic therapy for ABC. These results warrant further evaluation of gedatolisib added to standard-of-care, first-line therapy for HR+/HER2- ABC."

Journal • Breast Cancer • Dental Disorders • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Stomatitis • ER • HER-2 • PIK3CA

Ascending dose escalation of belzutifan plus palbociclib for previously treated advanced clear cell renal cell carcinoma (ccRCC): Phase 1/2 LITESPARK-024 study part 1. (ASCO-GU 2026) - P1/2 | "Clinical Trial Registry Number: NCT05468697. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

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

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

Phase I/Ib study of inavolisib (INAVO) alone and in combination with endocrine therapy ± palbociclib (PALBO) in patients (pts) with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced/metastatic breast cancer (HR+, HER2– LA/mBC): Analysis of hyperglycemia (HG) in prediabetic/obese pts. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03006172 Background: INAVO, a highly potent and selective PI3Kα inhibitor that also promotes degradation of mutated p110α, is approved by the FDA in combination with PALBO + fulvestrant (FULV) for PIK3CA-mutated, HR+, HER2–, endocrine-resistant advanced BC... Adults ≥ 18 years of age received INAVO alone (Arm A), + letrozole (LET) + PALBO (Arm B), + LET (Arm C), + FULV (Arm D), + FULV + PALBO (Arm E), or + FULV + PALBO + primary prophylactic metformin (Arm F)...The most common anti-HG medications were metformin (52.7%; biguanide; concomitant use in Arm F excluded), empagliflozin (25.5%; SGLT-2 inhibitor), sitagliptin (22.7%; DPP-4 inhibitor), and pioglitazone (13.6%; thiazolidinedione); insulin was used in 8.2% of pts... A high proportion of prediabetic/obese pts were included in GO39374. In most of these pts, HG was manageable with dose interruptions and oral anti-HG medications, most commonly metformin. Data support the use..."

Clinical • Combination therapy • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Obesity • Oncology • Solid Tumor • HER-2 • PIK3CA

SNV4818 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=320 | Recruiting | Sponsor: Pikavation Therapeutics, Inc. | Phase classification: P1 ➔ P1/2 | N=140 ➔ 320 | Trial completion date: Dec 2026 ➔ Jun 2027 | Trial primary completion date: Oct 2026 ➔ Apr 2027

Enrollment change • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • PIK3CA

Matricellular protein SMOC2 safeguards tubular integrity in acute kidney injury via integrin β3-dependent inhibition of CCND1-CDK4/6 axis. (PubMed, Mol Biomed) - "We show that SMOC2 expression is rapidly and robustly induced in renal tubules following exposure to aristolochic acid I (AAI) or cisplatin. Notably, pharmacological inhibition of CDK4/6 with palbociclib phenocopied the protective effects of SMOC2, with post-injury treatment providing superior protection, thus defining a druggable downstream pathway. Collectively, our findings uncover a previously unappreciated cytoprotective role of SMOC2 in AKI and establish the SMOC2-ITGB3-CCND1-CDK4/6 signaling axis as a potential therapeutic target to prevent AKI progression and its transition to CKD."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • CCND1 • CDK4 • ITGB3

Impact of Treatment Related Neutropenia on Response to Palbociclib in Metastatic Hormone Positive, her2neu Negative Breast Cancer. (PubMed, Asian Pac J Cancer Prev) - "Neutropenia induced by palbociclib and subsequent dose reduction did not impact the disease outcome."

Journal • 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 • CDK6 • HER-2

Kinetics and determinants of blood ESR1 mutation under AI and palbociclib in HR+/HER2- metastatic breast cancer patients in the PADA-1 trial (ESMO-BC 2025) - P3 | "Approximatively 40% of HR+/HER2- mBC patients treated with AI and palbociclib develop rising bESR1 mut before or at progression. Younger (premenopausal) patients and tumors with high ER expression exhibit a higher likelihood of rising bESR1 mut , suggesting oncogenic addiction to ER signaling. These findings support personalized bESR1 mut monitoring and highlight subgroups that could benefit most from next-generation SERDs in first-line therapy."

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

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

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

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

CDK4/6 inhibitors in low-grade serous ovarian carcinoma (LGSOC): a pooled analysis (ESGO 2026) - "MEK inhibitors (trametinib [1], selumetinib [2]) provide limited activity, while smaller studies evaluated BRAF and PI3K inhibition [3, 4]. More recently, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have emerged as a promising strategy [5–7].Methodology A systematic search of MEDLINE, Embase, and ClinicalTrials.gov (2000–2025) identified phase I/II or basket studies evaluating palbociclib, ribociclib, or abemaciclib in LGSOC...The highest activity was observed with ribociclib + letrozole in Colon-Otero et al...2025 achieved ~ 20 % ORR, while no responses occurred in the ribociclib + spartalizumab cohort (Garrido-Castro 2025)...Reported toxicity was predominantly haematologic, consistent with the known CDK4/6-inhibitor profile.Conclusion Endocrine-based CDK4/6 inhibition shows meaningful and durable disease control in LGSOC, with benefit rates exceeding those achieved by chemotherapy. Evidence remains limited and heterogeneous; ongoing..."

Retrospective data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

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