Docetaxel

FLEX Study data shows that patients with MammaPrint High Risk 2 tumors have improved 3-year survival with anthracycline-containing regimens, while patients with High Risk 1 tumors show no additional benefit IRVINE, Calif. & AMSTERDAM--(BUSINESS WIRE)--Agendia ® , Inc., a leader in precision oncology for breast cancer, today announced the publication of a new paper in JCO Precision Oncology, titled “Prediction of Anthracycline Benefit in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Early-Stage Breast Cancer by the MammaPrint 70-Gene Signature for Patients Enrolled in the FLEX Study.” The study, based on data from the prospective, real-world FLEX Study ( NCT03053193 ), found that MammaPrint ® + BluePrint ® can help identify a subset of patients with hormone receptor positive, HER2-negative (HR+HER2-) early-stage breast cancer (EBC) most likely to benefit from anthracycline-based chemotherapy. This research led to an update in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) recognizing MammaPrint as the only genomic test to guide personalized anthracycline use in this patient population. “Patients with HR+HER2-negative breast cancer who are candidates for adjuvant chemotherapy continue to face uncertainty around whether they will derive meaningful benefit from anthracycline-containing regimens,” said Joyce O’Shaughnessy, M.D., principal investigator for the FLEX Study. “This long-standing clinical dilemma underscores the need for predictive biomarkers that can identify which patients are most likely to benefit from anthracyclines and who may safely avoid unnecessary toxicity.” While anthracyclines are highly effective antitumor agents, they are associated with potentially serious toxicities, including cardiotoxicity and secondary leukemias. Multiple randomized controlled trials – including the ABC trials 1 , Plan B trial 2 , the MASTER trial 3 and the DBCG 07-READ trial 4 – have attempted to determine whether anthracycline-free chemotherapy regimens are non-inferior to anthracycline-containing regimens in clinically high-risk HER2-negative EBC but found no significant difference among HR+HER2- patients. This observational study from FLEX included 1,259 patients with stages I to III, HR+HER2- EBC, classified as MammaPrint High Risk 1 (H1) or High Risk 2 (H2) and BluePrint Luminal B, who received adjuvant chemotherapy with either anthracycline and taxane-based chemotherapy (AC-T) or adjuvant taxane with cyclophosphamide (TC), and had a median follow-up of 3.2 years. Inverse probability of treatment weighting (IPTW), a well-established statistical method for the analysis of real-world evidence, was performed to balance clinical characteristics between treatment groups and approximate the design of a randomized trial. Key findings from the study include: Patients with H2 tumors demonstrated significantly improved 3-year invasive disease-free survival (IDFS) with AC-T versus TC, with IDFS rates of 100% vs 94.8%, respectively – an absolute benefit of 5.2% (p=0.023). Patients with H1 tumors showed no significant difference in 3-year IDFS with identical IDFS rates of 95.9% for both regimens, despite overlapping high-risk clinical features. A statistically significant treatment-by-MammaPrint interaction demonstrated that AC-T benefit increased with higher genomic risk (p=0.036), showing that MammaPrint H2 is predictive of anthracycline benefit. “This study answers a question that randomized clinical trials have been unable to resolve, illustrating the value of genomic profiling to predict benefit from a specific cancer therapy,” said William Audeh, M.D., M.S., Chief Medical Officer of Agendia and co-author of the study. “The FLEX Study highlights the power of a multi-modal real-world evidence database to produce robust, clinically relevant data which not only inform treatment decisions, but also change clinical practice guidelines.” References 1. Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC Trials—USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017;35(23):2647-55. doi:10.1200/JCO.2016.71.4147 2. Nitz U, Gluz O, Clemens M, et al. West German Study PlanB Trial: Adjuvant four cycles of epirubicin and cyclophosphamide plus docetaxel versus six cycles of docetaxel and cyclophosphamide in HER2-negative early breast cancer. J Clin Oncol. 2019;37(10):799-808. doi:10.1200/JCO.18.00028 3. Yu KD, Liu XY, Chen L, et al. Anthracycline-free or short-term regimen as adjuvant chemotherapy for operable breast cancer: A phase III randomized non-inferiority trial. Lancet Reg Health West Pac. 2021;11:100158. doi:10.1016/j.lanwpc.2021.100158 4. Ejlertsen B, Tuxen MK, Jakobsen EH, et al. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017;35(23):2639-2646. doi:10.1200/JCO.2017.72.3494. About Agendia Agendia is a global leader in precision oncology focused on early-stage breast cancer . The company’s genomic assays, MammaPrint + BluePrint , deliver essential biological insights to inform personalized treatment decisions for patients and their care teams. With operations in Amsterdam and Irvine, Agendia partners with academic and community oncology centers worldwide to generate real-world evidence through the landmark FLEX Study (NCT03053193) , the largest whole-transcriptome registry of early-stage breast cancer. About MammaPrint MammaPrint is a gene expression profiling test that assesses a woman’s risk of distant metastasis in early-stage breast cancer. By analyzing 70 key genes in a tumor, it stratifies risk into four categories — UltraLow Risk, Low Risk, High Risk 1, and High Risk 2 — to help guide personalized treatment planning, including chemotherapy benefit and de-escalation decisions. About BluePrint BluePrint is an 80-gene molecular subtyping assay that reveals the functional biology driving tumor growth, classifying tumors as Luminal-type, HER2-type, or Basal-type. By defining intrinsic subtypes beyond traditional immunohistochemistry, BluePrint provides critical insights to optimize treatment selection and improve outcomes. Contacts Media contact marketing@agendia.com

Pfizer Inc. (NYSE: PFE) today announced topline results from the Phase 3 SigVie-002 study (previously known as Be6A Lung-01) evaluating sigvotatug vedotin, an investigational, potential first-in-class integrin beta-6 (IB6) directed antibody-drug conjugate (ADC). The study enrolled adults with locally advanced, unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) who had received one or more lines of prior therapy. In the overall population, sigvotatug vedotin did not show a statistically significant improvement in the primary endpoint of overall survival (OS) compared to docetaxel. The safety pro sigvotatug vedotin was manageable and consistent with prior studies. Encouragingly, in patients who received only one prior line of systemic therapy, which represents two-thirds of the study population, a stronger trend was observed for OS and progression-free survival (PFS) for sigvotatug vedotin over docetaxel. In the exploratory analysis, no clear IB6 expression-response relationship was observed. Detailed results from SigVie-002 will be submitted for presentation at a future medical congress. “Patients with previously treated advanced NSCLC are a historically difficult-to-treat population, and there is clearly more work to be done to improve the outcomes for this population,” said Jeff Legos, Chief Oncology Officer, Pfizer. “Although the overall study results did not demonstrate superiority over docetaxel, it is encouraging that second-line patients treated with sigvotatug vedotin achieved strong efficacy outcomes compared to an established standard of care, alongside a manageable safety profile. This observed clinical benefit, along with our Phase 1 combination data in the first-line setting, reinforces our confidence in the potential of the sigvotatug vedotin program, including an ongoing Phase 3 trial in combination with pembrolizumab in first-line advanced NSCLC.” “It is important not to underestimate the activity of docetaxel as a comparator in this setting. Patients enrolled in this trial were heavily pre-treated, with most having previously received both platinum-based chemotherapy and immunotherapy, yet docetaxel continues to provide meaningful clinical benefit. Although the study did not meet its overall survival endpoint, in second-line patients the data suggest a clinically meaningful survival benefit for sigvotatug vedotin over docetaxel, supporting continued scientific evaluation of sigvotatug vedotin in earlier lines in combination with immunotherapy,” said Solange Peters, M.D., PhD, Chair of Medical Oncology & Thoracic Cancers Clinic, Lausanne University Hospital, Switzerland. “The ability of sigvotatug vedotin to induce immunogenic cell death provides a strong rationale for combination approaches with immunotherapy, particularly in earlier treatment settings where immune competence is better preserved. In this context, the promising phase 1 efficacy signals observed in treatment-naïve patients with high PD-L1 expression warrant further evaluation and may represent a more effective clinical application of this strategy.” In NSCLC, IB6 is expressed on approximately 90% of tumors. IB6 is associated with poor prognosis. Sigvotatug vedotin is a novel ADC designed for high target selectivity of IB6 and rapid internalization, which may help limit binding to other integrins more likely to be expressed in normal tissues and potentially reduce off-target toxicity. Pfizer is evaluating sigvotatug vedotin in several ongoing studies across multiple stages and patient populations in NSCLC and other solid tumors, including: An ongoing Phase 3 study evaluating sigvotatug vedotin + pembrolizumab in 1L NSCLC with PD-L1 tumor proportion score (TPS) ≥50%; and Exploration of sigvotatug vedotin in novel combinations, including with PF’4404, the novel bispecific antibody targeting PD-1 and VEGF, in early-stage lung cancers and other IB6-expressing tumors. Since the acquisition of Seagen, Pfizer has continued to advance a broad ADC portfolio spanning marketed medicines and pipeline programs. Pfizer is progressing multiple differentiated ADC candidates, including fetrastobart vedotin, a PD-L1–directed ADC currently in Phase 3 in NSCLC, additional IB6-targeted ADCs with alternate payloads, and early-stage candidates exploring novel targets and payloads, including topoisomerase I (Topo1) inhibitors and novel auristatin-based payloads. This breadth reinforces the strength of Pfizer’s Oncology pipeline, including the potential for novel combinations with its investigational PD-1xVEGF bispecific antibody (PF-08634404), supporting the company’s goal of delivering 8 potential Oncology breakthroughs by 2030. SigVie-002 (NCT06012435) is an ongoing, open-label randomized, Phase 3, global study evaluating sigvotatug vedotin compared with docetaxel in adult participants with previously treated locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC). Patients were randomized to receive sigvotatug vedotin administered intravenously on Days 1 and 15 of each 28-day cycle or docetaxel administered intravenously on Day 1 of each 21-day cycle. The primary endpoint of this trial is overall survival (OS). The study enrolled 703 participants. Descriptive, secondary endpoints include progression-free survival (PFS), confirmed objective response rate (ORR) and duration of response (DOR) per RECIST v1.1 as assessed by blinded independent central review (BICR). At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, gastrointestinal cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For over 175 years, we have worked to make a difference for all who rely on us. The content above comes from the network. if any infringement, please contact us to modify.