Truqap (capivasertib) / Otsuka, AstraZeneca - LARVOL DELTA

Polatuzumab vedotin induced activation of B-cell receptor signaling creates a synthetic lethality with BTK and AKT inhibition in Mantle Cell Lymphoma (ASH 2025) - "Indeed, using a cross-titration-based drug synergy evaluation, we detected a strong and wide synergism between 1) PV andBTK inhibitor ibrutinib, and 2) PV pan AKT inhibitor capivasertib, both pending in vivo mice tumorxenograft model-based confirmation.Conclusion. Importantly, this anti-CD79B mediated cell growth stimulationcould be eliminated by combining PV with BCR signaling inhibition. Our data thus provide a strongfoundation for future research and preclinical testing of these therapeutic combinations.Supported by MHCR (DRO - VFN00064165), National Institute for Cancer Research (EXCELES -LX22NPO5102), and MEYSCR (Cooperatio, SVV 260637)."

Synthetic lethality • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • CASP3 • CASP7 • CD79B • IGH

HEM-ismart: An international proof-of-concept therapeutic stratification trial of molecular anomalies in relapsed or refractory hematological malignancies in children (ASH 2025) - "Evaluation of potential and enrolled patients, safety,toxicity and response data from on-study subjects are reviewed each week at the coordinating teammeetings to ensure sponsor oversight.Current subtrials include:Subtrial B: dasatinib, venetoclax (VEN) and dexamethasone (DEX) with cyclophosphamide (CP) andcytarabine (CA) for ABL1 fusion-driven disease (approved, will be activated in Q3 2025)Subtrial C: ruxolitinib, VEN and DEX with CP and CA for IL7R-mutant and JAK/STAT pathway-drivendisease(approved, will be activated in Q3 2025)Subtrial D: trametinib and DEX with CP and CA for Ras/MAPK pathway-driven disease (recruiting)Subtrial E: capivasertib, VEN and DEX for molecularly unselected patients (generic) andPI3K/AKT/mTOR-driven disease (in process of regulatory submission)To date, 2 subjects with R/R B-ALL and 1 with R/R T-ALL were enrolled in subtrial D.ConclusionHEM-iSMART is an international, academic, collaborative, precision-medicine, multi-arm platform trial..."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • ABL1 • BCL2 • CD22 • IL7R

Capivasertib (C) + paclitaxel (P) as first-line treatment of metastatic triple-negative breast cancer: The CAPItello-290 phase III trial extended China cohort (ESMO Asia 2025) - P3 | "OS and PFS numerically favoured C + P over pbo + P in pts with PIK3CA/AKT1/PTEN-altered tumours, but interpretation is limited by small sample size and wide confidence intervals. No new safety concerns with C + P were identified."

Clinical • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PIK3CA • PTEN

AKT inhibitors for advanced metastatic breast cancer: Meta-analysis of their efficacy and safety across hormone receptor (HR) and HER2 status-based subtypes (ESMO Asia 2025) - "Background: Trials combining novel AKT inhibitors, Capivasertib and Ipatasertib, within the standard therapy (SoC) of breast cancer have reported variable results across its subtypes. AKT inhibitors demonstrated favourable clinical response in the HR+/HER2- subtype when combined with endocrine therapy (fulvestrant), as well as in PI3K/AKT-altered subgroups within both HR+ and TNBC subtypes. Future trials should prioritize the enrolment of participants with PI3K/AKT alterations or other targetable molecular vulnerabilities to better assess their therapeutic potential."

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

Capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in patients (pts) with PTEN deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC): Phase III CAPItello-281 Chinese subgroup analysis (ESMO Asia 2025) - P3 | "rPFS and OS benefits with capi + abi vs pbo + abi were numerically greater in the Chinese subgroup vs the global population of CAPItello-281. The safety profile was also consistent with the global population and the known profiles of capi and abi. These results support the potential use of capi + abi in pts with PTEN deficient mHSPC from China mainland, Taiwan, and Hong Kong."

Clinical • Metastases • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PTEN

THE RAF/MEK INHIBITOR VS-6766 SHOWS EFFICACY IN RAS-MUTANT PEDIATRIC PRECLINICAL XENOGRAFT MODELS- A REPORT FROM THE PEDIATRIC PRECLINICAL IN VIVO TESTING CONSORTIUM (CTOS 2025) - "To evaluate drug combinations, RMS PDXs were treated with VS-6766 in doublet with 14 other drugs targeting additional areas of the MAPK/ERK pathway along with untreated control, VS-6766 alone, and vincristine + irinotecan (standard of care) for a total of 17 treatment groups...In combination testing, survival advantage was most notable when VS-6766 was combined with VS-4718 (FAK), everolimus (mTOR), copanlisib (PI3Kδ/α), capivasertib (AKT), BBP-398 (SHP2) and LY3023414 (PI3K) compared to VS-6766 alone. VS-6766 exhibited antitumor activity across several pediatric cancers... VS-6766 exhibited antitumor activity across several pediatric cancers. As single agent, there was activity in the majority of solid tumor models tested with prolongation of time on study and stabilization of disease. Solid tumor models harboring RAS mutations appear more likely to respond, although limited non-mutant models were tested."

Preclinical • Hematological Malignancies • Leukemia • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • HRAS • KRAS • NF1 • NRAS • PIK3CD

Tumor Microenvironmental NRG1 Drives Resistance to PI3K Pathway Inhibition in Prostate Cancer (SUO 2025) - "Cells were treated with PI3K pathway inhibitors (GDC-0941, Capivasertib, Sapanisertib) alone and in combination with enzalutamide, an androgen receptor inhibitor...In 22RV1 cell line xenografts, combination therapy with seribantumab, enzalutamide, and pictilisib significantly suppressed tumor growth compared to enzalutamide and pictilisib alone ( Figure 1D )... The TME-derived secretome plays a critical role in modulating resistance to targeted therapies in prostate cancer. NRG1 in the PCa TME, activates HER3 signaling and promotes resistance to both AR and PI3K pathway inhibitors. Targeting HER3 in combination with PI3K inhibitors represents a promising therapeutic strategy to overcome NRG1-mediated resistance mechanisms in advanced prostate cancer."

Biomarker • Tumor microenvironment • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • NRG1

Capivasertib plus fulvestrant in hormone receptor-positive (HR+) advanced breast cancer (ABC): exploratory ctDNA analyses from the Phase 3 CAPItello-291 trial (SABCS 2025) - "ctDNA analysis offers a minimally invasive option to identify PIK3CA/AKT1/PTEN alterations in HR+ ABC, particularly for pts without suitable tumor tissue analysis. However, ctDNA testing alone may miss alterations, such as in cases of low ctDNA shedding (TF <0.1%), warranting a confirmatory tissue test. The PFS benefit of C + F vs pbo + F in the ctDNA-altered group was consistent with the primary tissue-based analysis."

Circulating tumor DNA • Metastases • P3 data • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • CDK4 • HER-2 • PIK3CA • PTEN

Clinical and genomic biomarkers of capivasertib response in patients with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2- MBC) (SABCS 2025) - "In this study of patients with HR+/HER2- MBC treated with capivasertib and fulvestrant, alterations in CCND1 and ARID1A in ctDNA were associated with poorer PFS, while ESR1 and PI3K pathway co-mutations trended toward worse outcomes. Patients treated in the second-line or earlier, and those without prior PI3Ki exposure, may derive greater benefit. These findings are exploratory and warrant validation but suggest specific biomarkers that may correlate with risk for early progression on an AKT inhibitor."

Biomarker • 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 • AKT1 • ARID1A • CCND1 • ER • FGFR1 • HER-2 • PIK3CA • PTEN

Capitrue, capicorn, and capitana: three phase iiib studies to evaluate the use of capivasertib in combination with fulvestrant in patients with advanced breast cancer who have relapsed/progressed on endocrine therapy and cdk4/6 inhibitors reflecting real-world clinical practice in china, germany, belgium, portugal and spain. (SABCS 2025) - P3 | "This will enable the adaptation of CAPItello‑291 findings to diverse clinical practices and contribute to the development of globally and locally relevant oncology strategies. A joint analysis of the data gathered from the three studies is planned."

Clinical • Combination therapy • Metastases • P3 data • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

A prospective, direct-to-patient study to evaluate clinical and molecular mechanisms of resistance to capivasertib in estrogen receptor-positive metastatic breast cancer (SABCS 2025) - "PI3Kα inhibitors including alpelisib and inavolisib improve progression free survival (PFS) in PIK3CA-mutated ER+ MBC, but are often associated with high-grade toxicities such as hyperglycemia...In the CAPItello-291 trial, capivasertib combined with fulvestrant more than doubled PFS to 7.3 months versus 3.1 months with fulvestrant alone, and exhibited a favorable toxicity profile...Since January 2025, 10 patients have been enrolled and provided pre-treatment ctDNA samples. Further study details are available at https://contributeher.wixsite.com/capivaresistance."

Clinical • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • PIK3CA • PTEN

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

Investigating association of comorbidities and race with all-cause mortality outcomes of PI3K inhibitor use in metastatic breast cancer (mBC) (SABCS 2025) - "PI3K and AKT pathway inhibitors Alpelisib, Inavolisib, and Capivasertib (PI3K/AKTi) are FDA approved treatments with demonstrated significant clinical benefit, improving progression free survival for Hormone receptor positive (HR+) mBC. We did not identify disparities in mortality between our 3 racial cohorts. Future studies are needed to understand interactions between individual PI3K/AKTi agents and comorbidities to inform appropriate management strategies and ultimately improve patient outcomes."

Metastases • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Sequencing PIK3CA, AKT and mTOR Inhibitors in HR+/HER2- Metastatic Breast Cancer: A Real-World Retrospective Analysis (SABCS 2025) - "Approved agents—everolimus (mTOR inhibitor), alpelisib (PIK3CA inhibitor), and capivasertib (AKT inhibitor)—have demonstrated median progression-free survival (mPFS) ranging from 5.5 to 7.3 months in patients previously treated with CDK4/6 inhibitors. Our findings support the consideration of sequencing pathway inhibitors regardless of tolerance to the first agent. These results reinforce sequential PI3K/AKT/mTOR inhibition as a viable strategy in modern metastatic breast cancer care, though prospective studies are needed to validate this approach in pretreated populations."

Metastases • Real-world • Real-world evidence • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

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

Hypoxic Tumor Microenvironment Promotes Hippo Pathway Transcriptional Activity to Enrich Glioma Stem Cells in the Peri-necrotic Niche of Glioblastoma (SNO 2025) - "AKT inhibition with Capivasertib reduced Zyx phosphorylation and Hippo transcription in hypoxia...Blocking TGFBR2 with inhibitor LY2109761 abolished TGF-β1-induced Hippo activation...In vivo, pharmacologic inhibition of YAP/TAZ with Verteporfin or genetic TAZ knockdown in the RCAS/tv-a mouse model reduced tumor burden and prolonged survival. Flow cytometry confirmed decreased CD133+/CD44+ GSCs in TAZ-deficient tumors. These results demonstrate hypoxia and TGF-β1 signaling to activate YAP/TAZ-driven Hippo signaling, promoting GSC maintenance in the peri-necrotic GBM niche."

Biomarker • Tumor microenvironment • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CCN1 • CD133 • FOXM1 • OLIG2 • SOX2 • TAFAZZIN • TGFB1 • TGFBR2 • YAP1

Mechanisms of resistance to anti-HER2 therapies in brain metastatic derivatives of inflammatory HER2-positive breast cancer models (SABCS 2025) - "The HER2-selective tyrosine kinase inhibitor (TKI) tucatinib (Tuca) and the pan-HER TKI neratinib (Nrb), mostly used in the late line setting, are effective, including in treating brain metastases...Drug efficacy studies involved methylene blue-based cell growth and IC50 assays, and included the Akt inhibitor (i), capivasertib (Capi, 1uM), T-DXd (5ug/mL), and the EGFR-specific TKI gefitinib (Gef, 1uM) or monoclonal antibody cetuximab (Cetux, 10ug/mL)... Our findings suggest the role of high EGFR and PIK3CA mutations in resistance to Tuca, which warrants additional preclinical and clinical investigation. This underscores the importance of understanding if PIK3CA mutations are associated with reduced Tuca sensitivity and the testing of new mutant specific PIK3CAi or other PI3K/Akt pathway inhibitors. Our brain tropic TucaR cell and mouse models will be useful to understanding resistance in the brain metastatic setting, and future work will test the most promising..."

Metastases • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • PIK3CA

Co-targeting the PI3K-Akt pathway improves response to MEK inhibition in low-grade serous ovarian cancer cell lines. (PubMed, Gynecol Oncol) - "LGSOC responds to MEK inhibition by upregulating PI3K-Akt signaling, thereby promoting cell survival and proliferation. Our research identified significant upregulation of the PI3K-Akt pathway in response to MEK inhibition. While targeted inhibition of AKT had minimal impact alone, combination with MEK inhibitors produced strong synergistic suppression of proliferation in LGSOC cells. This combination strategy could potentially be used to prevent or reverse the emergence of MEK inhibitor resistance in LGSOC patients."

Journal • Preclinical • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

Comparative Analysis of PIK3CA, AKT1, and PTEN Reporting Across Commercial NGS Tests in Breast Cancer (BC) (SABCS 2025) - "Introduction: Genomic alterations in PIK3CA, AKT1 and PTEN are biomarkers for the AKT inhibitor Capivasertib (Capi), an approved treatment for metastatic BC (mBC) patients who progressed on ≥1 endocrine therapy or recurred during/within 12 months of adjuvant therapy... 29% (8/28) BC patients with on-label Capi alterations detected with F1CDx were not reported by Caris NGS tissue testing. 89% (8/9) of PTEN alterations were not reported by Caris NGS tissue testing, including all PTENloss and PTENre. 75% (6/8) Caris IHC PTEN results reported PTEN protein loss (not a current Capi indication)."

Next-generation sequencing • Breast Cancer • Oncology • Solid Tumor • AKT1 • PIK3CA • PTEN

Trends and Barriers in Biomarker Testing and Treatment Patterns in HR+/HER2- Metastatic Breast Cancer (SABCS 2025) - "Among pts with ESR1+, elacestrant use rose from 22% in 2023 to 29% in 2024 in 2L and remained steady at 26-27% in 3L. In AKT1/PTEN+ pts, capivasertib use was 6% in 2L and 11% in 3L in 2024...Timely testing was less common in smaller practices and lower-SES settings, highlighting systemic barriers to precision oncology. To close these gaps, coordinated, equity-focused strategies are needed to improve timely testing and ensure appropriate use of targeted treatments across all pts populations."

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

ReDiscover-2, a phase 3 study of RLY-2608 + fulvestrant versus capivasertib + fulvestrant as treatment for locally advanced or metastatic PIK3CA-mutant HR+/ HER2- breast cancer following recurrence or progression on or after treatment with a CDK4/6 inhibitor (trial in progress) (SABCS 2025) - P3 | "While the PI3K inhibitors alpelisib and inavolisib and the AKT inhibitor capivasertib have been approved by the FDA to treat this substantial patient population, these therapies cause significant toxicity, notably hyperglycemia, rash, and diarrhea, due to their non-selective targeting of the pathway. Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication are excluded• No prior PI3K, AKT, or mTOR inhibitors or any agent whose mechanism of action is to inhibit the PI3K/AKT/mTOR pathwayReDiscover-2 (NCT06982521) is open for enrollment. For further information, contact: clinicaltrials@relaytx.com."

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 • PIK3CA • PTEN

Real-world Treatment Patterns of Capivasertib in Metastatic Breast Cancer in the US (SABCS 2025) - "Prior therapies for MBC included: CDK4/6 inhibitors (87.1%), fulvestrant (66.0%), chemotherapy (31.8%), alpelisib (20.6%), and antibody-drug conjugates (14.1%) in any prior LOT. Findings from this large database analysis of US patients demonstrate the effectiveness of capivasertib + fulvestrant in real-world practice. Clinical outcomes in 2L and 3L closely match those observed in the CAPItello-291 Phase 3 randomized controlled trial, which supported FDA approval of the capivasertib + fulvestrant regimen. Numerically improved outcomes were observed in patients who used capivasertib in earlier vs later line settings."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • PIK3CA • PTEN

Real world outcomes of use of Capivasertib in patients with HR positive HER2 negative metastatic breast cancer: A single center study (SABCS 2025) - "In this single-center experience, the findings of CAPItello-291 was validated, that a combination of capivasertib and fulvestrant is an effective treatment in second or later-line therapy for metastatic HR+ HER2- breast cancer patients harboring AKT pathway alterations, with a similar discontinuation rate."

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 • PGR • PIK3CA • PTEN

Poor response to systemic therapy upon progression on cyclin dependent kinase 4/6 inhibitors in HR+ Inflammatory Breast Cancer (SABCS 2025) - "RESULTS Among N = 33 patients evaluated, upon progression on standard of care CDKI and endocrine directed therapy (ET) combinations, patients received the following therapies with median ToT (months (min-max ToT)), respectively: capecitabine (N = 7; 3 (2-5)), everolimus/ET (N = 6, 3 (1-4)), Abraxane (N = 3, 3(2-10)), Eribulin (N = 2, 2.5(2-3)), capivasertib/fulvestrant (N = 1, 6(6)), taxol (N = 1, 5(5)), elacestrant (N = 1, 3(3)), fulvestrant (N = 1, 3(3)), tamoxifen (N = 1, 1(1)), intrathecal topotecan (N = 1, 1(1)), non standard/clinical trial (N = 4, 2.5(1-4)). CONCLUSION Patients with metastatic HR+ IBC demonstrate poor response to ET and cytotoxic chemotherapies upon progression on first line standard CDKI/ET, with a disproportionately high rate of death occurring in the first line setting due to advanced disease. Given previously reported low ToT on CDKI/ET in the first line and high incidence of brain relapse in this population, clinical trial design utilizing..."

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

Therapeutic Implications of Concurrent ESR1 and PI3K Pathway Mutations in HR+/HER2- Metastatic Breast Cancer (SABCS 2025) - "Likewise, alpelisib and capivasertib improved PFS in patients with PIK3CA-mutated, HR+, HER2- advanced breast cancer who had progressed on prior endocrine therapy.Little is known about the clinical significance of concurrent ESR1 and PIK3CA mutations in breast cancer patients...However, our data uniquely demonstrates that patients with concurrent ESR1 and PIK3CA mutations, who were treated initially with PIK3CA inhibitor followed by elacestrant, had longer PFS and OS. This sequencing may offer improved outcomes, as PI3K mutations may confer a worse prognosis than ESR1 mutations. Prior studies, including EMERALD and EMBER-3, have indicated shorter PFS in patients with PI3K mutations treated with oral SERDs compared to those without PI3K pathway alterations.These findings highlight the need for future studies comparing institutional data across larger cohorts and prospective trials to better define optimal sequencing strategies for this subset of patients."

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 • PIK3CA