Baseline characteristics of patients with transthyretin amyloid cardiomyopathy enrolled in a tafamidis expanded access programme

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and ultimately fatal disease caused by the accumulation of amyloid fibrils in the heart muscle. Tafamidis, currently the only approved drug for the treatment of ATTR-CM, demonstrated reduced mortality and cardiovascular-related hospitalisations in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). Real-world data in patients with ATTR-CM, including patient characteristics, are scarce. Here we analysed the baseline characteristics of patients enrolled in an expanded access programme (EAP) for tafamidis. Initiated in 2018, this tafamidis EAP allows access to tafamidis for patients who have exhausted all standard-of-care options and are not eligible for a clinical trial. Purpose To examine baseline characteristics of patients with ATTR-CM enrolled in a tafamidis EAP. Methods All patients enrolled in this tafamidis EAP from the start (May 2018) until November 2020 were included. To be eligible for inclusion, patients had to have documentation of the following: genetic testing for transthyretin amyloidosis (TTR sequencing); ATTR-CM diagnosis, including the criteria used; exclusion of light chain amyloidosis; and current medical/cardiac status, including New York Heart Association (NYHA) functional classification. Patients were grouped for analysis purposes in the following NYHA classes: I–II, >II–III, and >III–IV. Results A total of 700 patients (88.7% male) from 20 countries were enrolled over 2.6 years. Mean age was 76.2 years in males and 76.6 years in females. Of 518 patients with a recorded genotype, 87.5% were wild-type (89.6% male) and 12.5% hereditary (73.8% male). In males and females, respectively, mean age was 77.0 and 79.4 years in wild-type patients, and 66.2 and 69.3 years in variant patients. The NYHA class distribution is shown in the Figure. The greatest proportion of patients was considered NYHA class I–II. The proportion of patients considered NYHA class I–II was lower in the first half of the data collection period (Months 0–15, 55.3%) compared with the latter half (Months 15–30, 59.4%). In 254 patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) data, the median NT-proBNP level was 2784.5 pg/mL (NYHA class I–II, 2408.5 pg/mL; NYHA class >II–III, 3165.0 pg/mL). Conclusions These are the first multi-country, real-world data evaluating baseline characteristics of patients with ATTR-CM enrolled in an EAP. It is of interest that, compared with the ATTR-ACT population, this patient group was older and had a greater proportion of wild-type patients. As a higher percentage of patients with less severe disease was enrolled in the latter half of data collection, these data also suggest a potential shift over time to earlier diagnosis of ATTR-CM. This analysis provides insight into the characteristics of real-world patients with ATTR-CM. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer Figure 1. Baseline NYHA class distribution

Effect of gender on the outcome of patients receiving nivolumab for metastatic renal cancer: Results from a large study population.

e16087 Background: Several studies, the majority on melanoma and lung cancer, have addressed the value of gender with respect to immune check point inhibitors outcome as compared to standard therapy, showing conflicting results. Nevertheless, few focused on gender-related clinical outcome and toxicity in renal cell carcinoma (RCC) patients. Methods: This analysis evaluated the effect of gender on overall survival and adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 in an expanded access programme of nivolumab 3 mg/kg once every 2 weeks in second-line and beyond metastatic RCC. Only patients assuming at least one dose of nivolumab were analyzed. Results: Of 389 patients analyzed, 25.2% were female. On study entry, no differences were found in women as compared to men in terms of age, on average 64 years, p = 0.91; overweight/obesity, 45 versus (vs) 49%, p = 0.47; LDH , mean U/L 391 vs 32, p = 0.17); and neutrophils/lymphocytes ratio> 3 (62 vs 63%, p = 0.87). Disease presentation was similar according to gender, although women tended to present less lung (66% vs 76%, p = 0.06) and bone metastases (42% vs 52%, p = 0.07). Notably, there was no differences in the IDMC prognostic model by gender (p = 0.94). Any drug related AEs (38 vs 30%, p 0.15), grade 3-4 (6% vs 6%) and median number of drug doses 12 (53% vs50%, p = 0.58 ) did not differ between gender. After adjusting for known prognostic variables, multivariate analysis showed that women had similar overall survival as compared to men (hazard ratio 0.81, 95% confidence interval 0.56-1.17, p = 0.26). Conclusions: Women demonstrate similar overall survival than men in metastatic RCC treated with secondal line and beyond nivolumab, with no differences observed in serious AEs and dose administered.

Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer

BackgroundThe complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network.Materials and methodsPatients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit. They underwent comprehensive next generation sequencing (NGS) of either tumour tissue or cell-free circulating tumour DNA (ctDNA) or both. The MTB expressed either a positive or negative opinion for the treatment of the patients with discovered druggable alterations inside a clinical trial, in an expanded access programme, with a compassionate use. Afterwards, discovered alterations were matched with OncoKB levels of evidence for the choice of alteration-specific treatments in order to compare MTB outcomes with a standardised set of recommendations.ResultsNGS was performed either on ctDNA or tumour tissue or in both of them in 204 patients. The MTB evaluated 173 of these cases. Overall, the MTB proposed alteration-specific targeted therapy to 72 patients (41.6%). 49 patients (28.3% of the total evaluated) were indicated to enter a clinical trial. In 29 patients with matched liquid biopsy NGS (lbNGS), tumour tissue NGS (ttNGS) and MTB evaluation, the MTB changed the treatment strategy coming from standardised recommendations based on lbNGS and ttNGS alone in 10 patients (34.5%), thanks to the evaluation of other clinical parameters. In our cohort, lbNGS was more likely, compared with ttNGS, to detect point mutations (OR 11, 95% CI 2.9 to 24.1, p<0.001) and all-type alterations (OR 13.6, 95% CI 5.5 to 43.2, p<0.001) from the same genes of matched patients.ConclusionsOur MTB allows patients with refractory cancer to be included in clinical trials and improves the precision of clinical decisions compared with a standardised set of mutation-driven recommendations.