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Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib.
Genome Med
December 2024
Translational Medicine, Oncology R&D, AstraZeneca, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge, CB2 0AA, UK.
Background: The introduction of poly(ADP-ribose) polymerase (PARP) inhibitors represented a paradigm shift in the treatment of ovarian cancer. Genomic data from patients with high-grade ovarian cancer in six phase II/III trials involving the PARP inhibitor olaparib were analyzed to better understand patterns and potential causes of genomic instability.
Patients And Methods: Homologous recombination deficiency (HRD) was assessed in 2147 tumor samples from SOLO1, PAOLA-1, Study 19, SOLO2, OPINION, and LIGHT using next-generation sequencing technology.
Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial.
Lancet Oncol
November 2024
Helsicore Israeli Georgian Medical Research Clinic, Tbilisi, Georgia.
Article Synopsis
- The SERENA-2 trial investigates the efficacy of camizestrant, a new oral selective estrogen receptor degrader, compared to the traditional injectable SERD, fulvestrant, in treating advanced hormone receptor-positive breast cancer in post-menopausal women.
- This phase 2 trial includes patients who have experienced disease progression after previous endocrine therapies and assesses different dosages of camizestrant against fulvestrant, focusing on progression-free survival rates as the primary outcome.
- Conducted across 74 centers worldwide, the study also monitors the safety and side effects of the treatments among all participants who received at least one dose.
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors.
Nature
November 2024
Department of Thoracic and Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Article Synopsis
- Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
- Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
- The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet
October 2024
Gynelogic Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Article Synopsis
- - The phase 3 study ENGOT-cx11/GOG-3047/KEYNOTE-A18 found that adding pembrolizumab to standard chemoradiotherapy significantly improved progression-free survival in patients with advanced cervical cancer during the first interim analysis.
- - In this study, 1060 patients with high-risk cervical cancer were randomly assigned to receive either pembrolizumab or a placebo alongside chemoradiotherapy, with treatment outcomes evaluated at the second interim analysis.
- - The primary outcomes measured were progression-free survival and overall survival, focusing on patient mortality, with safety being a secondary consideration.
A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of groups 1, 2, and 3, and primary analysis of fixed-dose treatment group 6.
J Am Acad Dermatol
January 2025
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Article Synopsis
- - The phase 2 EMPOWER-CSCC-1 study showed that cemiplimab is effective against advanced cutaneous squamous cell carcinoma (CSCC), specifically in metastatic and locally advanced cases.
- - The study involved different treatment groups receiving either weight-based or fixed-dose cemiplimab, with a significant overall response rate (ORR) of 47.2% after 42.5 months and noted long-duration responses.
- - While the findings are promising, the study's limitations include its nonrandomized design and the fact that the primary endpoint was not based on survival rates.
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