7 research outputs found
The evolving role of PARP inhibitors in advanced ovarian cancer
The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase (PARP) inhibitors, which present greater inhibition effect in epithelial subtype due to high rates of homologous recombination deficiency. PARP inhibition exploits this cancer pitfall by disrupting DNA repair, leading to genomic instability and apoptosis. Three PARP inhibitors (olaparib, niraparib, and rucaparib) are now approved for use in women with epithelial ovarian cancer, while others are under development. Among women with BRCA1/2 mutations, maintenance PARP therapy has led to a nearly fourfold prolongation of PFS, while those without BRCA1/2 mutations experience an approximately twofold increase in PFS. Differences in trial design, patient selection and primary analysis population affect the conclusions on PARP inhibitors. Limited OS data have been published and there is also limited experience regarding long-term safety. With regard to toxicity profile, there are no differences in serious adverse events between the experimental and control groups. However, combining adverse event data from maintenance phases, a trend towards more events in the experimental group, compared with controls, has been shown. The mechanisms of PARP-inhibitor resistance include restoration of HR through reversion mutations in HR genes, leading to resumed HR function. Other mechanisms that sustain sufficient DNA repair are discussed as well. PARP inhibitors play a pivotal role in the management of ovarian cancer, affecting the future treatment choices. Defining exactly which patients will benefit from them is a challenge and the need for HRD testing to define ‘BRCA-ness’ will add additional costs to treatment
Real-World Data on Thromboprophylaxis in Active Cancer Patients: Where Are We? Are We Getting There?
Background: Cancer patients are at high risk for cancer-associated thrombosis (CAT). CAT is the second leading cause of death in these patients but it can be preventable with thromboprophylaxis. Patients and Methods: An observational, prospective, multicenter study aiming to record CAT management in clinical practice was conducted by the Hellenic Society of Medical Oncology (HeSMO). Results: A total of 426 active cancer patients (mean age 65.3 years, mean BMI: 26.1 kg/m2) who received thromboprophylaxis, were included from 18 oncology units. Tumor types were lung 25.1%, pancreas 13.9%, breast 8.7%, stomach 8.5%, ovarian 7.8%, and others 36%, while 69% had metastases. A total of 71% had a Khorana score ≤2 and 61% received High Thrombotic Risk Chemotherapy Agents (HTRCAs, e.g., platinum). For thromboprophylaxis patients received mainly Low Molecular Weight Heparins (LMWHs), on higher than prophylactic doses in 50% of cases. Overall, 16 (3.8%) thrombotic events and 6 (1.4%) bleeding events were recorded. Notably, patients on higher doses of LMWHs compared to patients who received standard prophylactic doses had 70% lower odds to develop thrombotic events (OR: 0.3, 95% CI: 0.10–1.0, p = 0.04). Conclusion: CAT is an important issue in oncology. Along with the Khorana score, factors as metastases and use of HTRCAs should also be taken into consideration. Thromboprophylaxis for active cancer patients with LMWHs, even on higher doses is safe and efficient
A Real-World, Observational, Prospective Study to Assess the Molecular Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations upon Progression on or after First-Line Therapy with a First- or Second-Generation EGFR Tyrosine Kinase Inhibitor in EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer: The ‘LUNGFUL’ Study
Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas®EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings
A Real-World, Observational, Prospective Study to Assess the Molecular Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations upon Progression on or after First-Line Therapy with a First- or Second-Generation EGFR Tyrosine Kinase Inhibitor in EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer: The `LUNGFUL' Study
Simple Summary Non-small cell lung cancer (NSCLC) accounts for
approximately 85% of lung cancer cases, with few patients carrying
driver mutations in the gene encoding for epidermal growth factor
receptor (EGFR). Advances in translational research have established
EGFR tyrosine kinase inhibitors (TKIs) as the standard first-line
therapy for NSCLC patients with activating EGFR mutations. The aim of
our observational study was to assess the frequency of T790M acquired
resistance and predictors of its presence, in patients with EGFR-mutated
locally advanced or metastatic NSCLC who have progressed in the
first-line EGFR-TKI treatment setting with first- or second-generation
TKIs and have undergone molecular testing in tissue and/or plasma
biopsy. The study highlights the challenges of performing tissue
re-biopsy in routine care settings, which can lead to patients
considered non-eligible for certain therapies from which they can
benefit, and merits further actions from the healthcare community, in
order to establish re-biopsy as a standard procedure. Background:
Real-world data on the molecular epidemiology of EGFR resistance
mutations at or after progression with first- or second-generation
EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This
ongoing observational study was carried out by 23 hospital-based
physicians in Greece. The decision to perform cobas EGFR Mutation Test
v2 in tissue and/or plasma at disease progression was made before
enrollment. For patients with negative/inconclusive T790M plasma-based
results, tissue re-biopsy could be performed. Results: Ninety-six (96)
eligible patients were consecutively enrolled (median age: 67.8 years)
between July-2017 and September-2019. Of the patients, 98% were tested
upon progression using plasma and 2% using tissue/cytology biopsy. The
T790M mutation was detected in 16.0% of liquid biopsies. Tissue
re-biopsy was performed in 22.8% of patients with a T790M-negative
plasma result. In total, the T790M positivity rate was 21.9%, not
differing between patients on first- or second-generation EGFR-TKI.
Higher (>= 2) ECOG performance status and longer (>= 10 months) time to
disease progression following EGFR-TKI treatment initiation were
associated with T790M positivity. Conclusions: Results from
plasma/tissue-cytology samples in a real-world setting, yielded a T790M
positivity rate lower than previous reports. Fewer than one in four
patients with negative plasma-based testing underwent tissue re-biopsy,
indicating the challenges in routine care settings