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  • ||||||||||  Ibrance (palbociclib) / Pfizer, Trodelvy (sacituzumab govitecan-hziy) / Everest Medicines, Gilead
    Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_967;    
    During the study period, the overall value of payments increased. She tolerated one week of tamoxifen which was discontinued due to adverse effects...Patient was started on letrozole with lupron and palbociclib with disease control for two years until progression in the bone, prompting a switch of letrozole to fulvestrant with continued palbociclib...She was then started on single-agent paclitaxel...She opted to enroll into a Phase 1b/2 trial with sacituzumab govitecan-hziy in combination with a PARPi...A history of mixed response in the liver was concluded to be two coexisting neoplasms
  • ||||||||||  Ibrance (palbociclib) / Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
    Proteogenomic approaches for the identification of NF1/neurofibromin-depleted estrogen receptor positive breast cancers for targeted treatment (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_897;    
    Blocking both pathways by fulvestrant (F), a selective ER degrader (SERD), together with binimetinib (B), a MEK inhibitor, promotes tumor regression in NF1-depleted ER+ models...MS showed that NF1 can also directly and selectively bind to palbociclib-conjugated beads, aiding quantification...Combined IHC and MS analysis defined a threshold of NF1 protein loss in ER+ breast PDX, below which tumors regressed upon treatment with B+F. These results suggest that we now have a MS-verified NF1 IHC assay that can be used for patient selection as a complement to somatic genomic analysis.
  • ||||||||||  Which treatment is done in patients with metastatic breast cancer who received a prior treatment with CDK4/6 inhibitors? A real-world experience in a single italian Institution (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_788;    
    105 mBC patients, 32 of whom were treated with CD4/6 inhibitors plus letrozole and 73 treated with CDK4/6 inhibitors and fulvestrant were included in the study...1 (0.95%) patients was treated with a triplet chemotherapy regimen (cyclophosphamide+capecitabine +vinorelbine), 2 (1.9%) for whom the re-biopsy of the tumor resulted HER2 + were treated with taxol +pertuzumab +trastuzumab...The major part of them have been treated with chemotherapy alone or with combination of more chemotherapies. The evaluation of the patient response in relation to the different therapies is still ongoing as well as the effect of all the other therapies beyond the first line of treatment.
  • ||||||||||  Ibrance (palbociclib) / Pfizer, adavosertib (AZD1775) / AstraZeneca
    Dual Inhibition of WEE1 and PKMYT1 Synergistically Overcomes CDK4/6 Inhibitor Resistance in Breast Cancer (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_781;    
    Overall, this study highlights the potential therapeutic benefits of dual inhibition of WEE1 and PKMYT1 in overcoming CDK4/6 inhibitor resistance in TNBC and ER+ve breast cancer patients. These findings provide a rationale for future clinical trials aimed at exploring the clinical utility of this combination therapy.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Activity of alpelisib in a panel of breast XPDX models harboring hotspot and uncommon PIK3CA mutations (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_705;    
    We have benchmarked a panel of PIK3CA-mutated breast XPDX models with alpelisib and compared activity of models harboring hotspot versus uncommon PIK3CA mutations with ER and HER2 expression. This data is a valuable tool in further developing PIK3CA inhibitors and identifying new variant targets in breast cancer.
  • ||||||||||  Ibrance (palbociclib) / Pfizer
    Evaluating the role of CDK4/6 inhibition on STAT3 activation in a transgenic mouse model of HER2-positive breast cancer (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_699;    
    We also demonstrate the anti-tumor effect of palbociclib in primary tumors with HER2-dependent proliferation. Taken together, our findings suggest that pSTAT3 is a viable therapeutic target and provides the rationale for combination therapy with CDK4/6 inhibition using palbociclib and STAT3 inhibition with a novel STAT3 inhibitor in HER2-positive breast cancer.
  • ||||||||||  Ibrance (palbociclib) / Pfizer, Kisqali (ribociclib) / Novartis, BLU-222 / Blueprint Medicines
    Combination treatment with CDK2 inhibitor (BLU-222) and either palbociclib or ribociclib is synergistic in pre-clinical models of CDK4/6 inhibitor-resistant breast cancer (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_632;    
    The efficacy of BLU-222 as a single agent or in combination with palbociclib or ribociclib was also assessed in two PDX models (PR 1 and 2) from patients with acquired resistance (i.e. progressed following >6 months of treatment) to palbociclib plus letrozole treatment, and another two PDX models (PR 3 and 4) from patients who were intrinsically resistant (i.e. progressed following < 3 months of treatment) to palbociclib plus fulvestrant or letrozole, respectively. These results show robust activity of BLU-222 in combination with CDK4/6 inhibitors in breast cancer cell lines and PDX models resistant to CDK4/6 inhibitors, providing a strong rationale for advancing BLU-222 plus CDK4/6 inhibitor treatment to clinical development in HR-positive/HER2-negative breast cancer patients who have progressed on CDK4/6 inhibitors.
  • ||||||||||  Prolia (denosumab) / Amgen, Daiichi Sankyo
    Denosumab vs. Pamidronate in the Management of Osteolytic Bone Metastases Secondary to Breast Cancer, a Multi-Institutional Analysis. (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_564;    
    The results of this study showed that Denosumab had a statistically insignificant risk reduction in both pathological fracture (2.7% vs. 2.8%, p = 0.88) and spinal cord compression (2.6% vs. 2.7%, p = 0.88) and a statistically insignificant difference in the overall five-year survival rate (45.5% vs. 52.4%, p = 0.78) when compared to Pamidronate. As a result, additional factors such as financial cost, route of administration, dosing schedule, and potential adverse side effects should be discussed with each individual who requires pharmacological therapy for bone metastases secondary to breast cancer.
  • ||||||||||  Prolia (denosumab) / Amgen, Daiichi Sankyo
    Impact of Discontinuation of Denosumab on Bone Health in Breast Cancer Patients (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_559;    
    It appears superior in reduction of SREs versus zoledronic acid (ZA) in established skeletal metastatic disease; thus, a preferred choice in the oncology setting...She was treated with neoadjuvant trastuzumab, pertuzumab, taxotere and carboplatin followed by bilateral mastectomy, and radiation to chest wall and L1...Bone modifying agents are often discontinued without consideration of the negative impact this may have. As this is a major survivorship issue, we document this case with literature review, to raise awareness for oncologists prescribing these medications.
  • ||||||||||  Ibrance (palbociclib) / Pfizer, Kisqali (ribociclib) / Novartis, Verzenio (abemaciclib) / Eli Lilly
    Clinical effectiveness of CDK4/6 inhibitors in HER2-low metastatic breast cancer (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_482;    
    Table 1 Baseline characteristics of patients with MBC comparing HER2-0 vs HER2-low, above/below median HER2/CEP17 ratio, and above/below median HER2 GCN. Table 2 Median OS and PFS in patients with MBC comparing HER2-0 vs HER2-low, above/below median HER2/CEP17 ratio, and above/below median HER2 GCN.
  • ||||||||||  Ibrance (palbociclib) / Pfizer, Kisqali (ribociclib) / Novartis, Verzenio (abemaciclib) / Eli Lilly
    CDK4/6 inhibitor-induced Interstitial Lung Disease (ILD) - A Case Series (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_476;    
    The overall risk of ILD was 1.6% in a meta-analysis of over 16,000 patients treated with CDK4/6 inhibitors while individual reported risk was 1%, 1.6% and 3% for palbociclib, ribociclib, and abemaciclib respectively...She started on palbociclib and letrozole and subsequently had 2 hospitalizations for acute hypoxemic respiratory failure with unremarkable infectious workup...The patient initially received taxol with near resolution of disease on imaging...Patient was switched to fulvestrant; and after 9 months she was diagnosed with stage IV tongue cancer and her breast cancer therapy was discontinued...It is important to identify early by performing a thorough workup, including a detailed history and physical exam, medication list review, infectious work-up, chest imaging, PFTs and pulmonology consultation. Publishing a set of standardized guidelines to diagnose and treat CDK4/6 inhibitor-induced ILD is necessary as more cases are identified.
  • ||||||||||  Ibrance (palbociclib) / Pfizer, onvansertib (PCM-075) / Cardiff Oncology
    PLK1 Inhibitor Onvansertib Extends the Response and Overcomes Resistance to Paclitaxel in Palbociclib-resistant HR+ Breast Cancer Patient-derived Xenografts. (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_472;    
    P1/2
    Notably, the antitumor activity of the onvansertib and paclitaxel combination was very durable, showing a robust delay in tumor relapse after stopping therapy. Together, our data strongly support that combining paclitaxel with the PLK1 inhibitor onvansertib extends its benefit and overcomes paclitaxel resistance, and represents a promising therapeutic strategy for HR+ breast cancer patients after progression on a combination of endocrine and CDK4/6 inhibitor therapy.
  • ||||||||||  Prolia (denosumab) / Amgen, Daiichi Sankyo, Kanjinti (trastuzumab-anns) / Amgen, Daiichi Sankyo, AbbVie, Perjeta (pertuzumab) / Roche
    Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_450;    
    The impact of weight on the outcomes with fixed-dose oral drugs warrants further investigation in future studies. The trial randomized 780 patients twice to a total of 4 treatment groups (to receive or not receive denosumab; to receive nab-paclitaxel 125 mg/m2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles, both followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2 every 2 weeks/every 3 weeks according to the investigator