ABSTRACT
Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over recent years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. There is ongoing discussion amongst oncology professionals about how best to optimise treatments in terms of sequencing to maximise the potential number of lines or to give the best treatments first. A previous south-west UK audit was completed in 2021 reviewing the drop off rates across 5 UK sites identifying that 69% of patients were able to receive second line therapy and 34% were able to receive third line therapy. Method(s): In this study we conducted retrospective analysis of all patients who commenced treatment with SACT for mRCC between 1st January 2018 and 30th June 2021 in 18 centres across the 4 nations of the United Kingdom. All NHS reimbursed treatment options including the COVID interim treatment guideline options were included. Patients who received SACT as part of a clinical trial were also included. Patients who continued on their respective lines of treatment were censored. We also identified patients who had been on a period of active surveillance before staring SACT in this cohort. Result(s): 1549 patients (71% male: 29% female) were included. IMDC subgroup patients included 21.6%favourable, 52.3% intermediate, 25.1%poor and 1% unavailable. 9.1% of patients had been on active surveillance before starting SACT - defined as a period of longer than 3 months from mRCC diagnosis to starting SACT. Of those patients that started SACT 60.5% of eligible patients had 2nd line therapy, 25.3% had 3rd line, 7.2% received 4th line therapy and only 1% had 5th line therapy. In the 1st line setting 58.9% received single agent VEGF TKI, 24.5% received combination ipilimumab and nivolumab (IO-IO) immunotherapy, 14 % received IO/ VEGF TKI combination and 2.6% received other/trial treatment. The single agent VEGF TKI ratio for 1st line SACT declined year by year with rising IO-IO and IO/VEGF TKI combination ratios seen. In the secondand third-line settings cabozantinib (33.2% 2nd line and 44.4% 3rd line) and nivolumab (32.8% 2nd line and 22.6% 3rd line) were the most common options. Disease progression or death was the most common cause of SACT discontinuation amounting to 57.4%, 62.5% and 79% of SACT cessation in the 1st, 2nd and 3rd lines respectively. Treatment toxicity SACT discontinuation rates were 22.8%, 21.4% and 10.9% for 1st, 2nd and 3rd lines respectively. Conclusion(s): These results suggest that with more treatment options available, including combination/immunotherapy therapies, more patients are able to receive second- and third-line therapies. That said there remains significant drop off rates mostly driven by disease progression that would support the use of our most effective therapies in the upfront setting.
ABSTRACT
Background: The RECORD Study is a real world data, prospective evaluation of clinical outcomes in patients with nmCRPC treated with Darolutamide. This study will increase the understanding of treatment response and management and in particular informregarding use of next generation imaging in this setting. Method(s): Patient data from 9 UK centres was collected based on the recommendation of NICE for Darolutamide as an option for the treatment of non-metastatic castrate resistant prostate cancer (nmCRPC) from November 2020. Data cut-off was 15 September 2022. The study is ongoing. Result(s): 87 patients were analysed with a median age of 78 (range 61-92). Median pre-treatment PSA and PSA doubling time (PSAdT) were 13 (range 1.99-110.6) mg/L and 5.05 (range 0.6 -10) months. 42 patients (49.4%) had pre-treatment PSAdT of <6 months and 43 (50.6%) patients had PSAdT of >=6 months (2 patients had no pre-treatment PSAdT data). 6 patients (6.90%) had next generation imaging prior to initiation of Darolutamide. Median duration of treatment on Darolutamide was 17 months for patients with pre-treatment PSAdT <6 months but median duration had not been reached for patients with pre-treatment PSAdT >=6 months after 24 months of treatment, a significant difference p=0.018 (HR=0.385, 95% CI 0.17-0.88). 30 patients have come off treatment so far (34.5%);21 (70%) for disease progression, 5 (16%) for a medical cause unrelated to the drug (e.g. COVID infection, reduced performance status secondary to pre-existing Parkinson's), 3 (10%) for unacceptable toxicity (rash, Grade3 fatigue, muscle aches, memory issues), and 1 patient died (unrelated). Conclusion(s): In the RECORD study, predominantly the diagnosis of nmCRPC is based on conventional imaging. The majority of patients respond and tolerate Darolutamide well, comparable with the ARAMIS trial. There is a significant difference between time on Darolutamide for those with pre-treatment PSAdT of<6 months compared with>=6 months. Further long-term toxicity, MFS and OS data will continue to be collected prospectively within the study.
ABSTRACT
Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over the last few years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. A previous real world study in the UK had demonstrated a significant attrition rate between each line of therapy suggesting less than half of patients who received first line SACT then received second line therapy and less than a fifth of first line SACT patients reach third line. Methods: We conducted a retrospective analysis of all patients treated between January 2018 and end of June 2021 to see if advancement in treatment options had impacted on the drop-off rates. Data was collected from 5 UK sites. Patients were identified from electronic SACT database. All reimbursed treatment options including the COVID interim treatment guidelines options were included. Patients who received SACT as part of a clinical trial were also included. Patients who remained on the respective lines of treatment were censored. Results: Data for 515 patients (372 male: 143 female) who received first-line SACT for mRCC were included in the analyses. IMDC prognostic groups were 103 favourable, 236 intermediate, 127 poor (49 not available). On progression 69% of patients were able to receive second-line therapy and 34% were able to receive third-line therapy. Of the 515 first-line therapies, 24% of patients received frontline ipilimumab and nivolumab, 10% received TKI and IO combination and 63% received single agent VEGF TKI. Second-line nivolumab or cabozantinib (43% and 40% respectively) were the most commonly prescribed options. Third-line cabozantinib 61% and nivolumab 16% remain the most used options. Across all lines of therapy progressive disease was the primary reason for discontinuation. 5% switched treatment due to toxicity. Conclusions: These results suggest that, with more treatment options available, including combination/ immunotherapy therapies, more patients are able to receive second and third-line therapies. Despite this, nearly one third of patients only receive one line of treatment which highlights the need to deliver the most efficacious treatments first to optimise patient outcomes. Moreover, single agent TKI was the most commonly used first-line SACT despite advances in the management pathway. Data analysing the impact of COVID on treatment selection will be presented.
ABSTRACT
Background: Paclitaxel is commonly used as first line chemotherapy for HER2 negative MBC. However, with response rates of 21.5-53.7% and a significant risk of peripheral neuropathy there is a need for more effective and better tolerated chemotherapy (CCT). Methods: This open label randomised (1:1) phase 2 trial compared 6 cycles of cabazitaxel (25 mg/m2 ) every 3 weeks, with weekly paclitaxel (80mg/m2 ) over 18 weeks as first line CCT. HER2 negative and performance status ≤1 patients were eligible. Patients on cabazitaxel received GCSF prophylaxis. Primary endpoint was Progression Free Survival (PFS) with 127 events required to detect a hazard ratio (HR) of 0.65 with 85% power. Secondary endpoints included objective response rate (ORR;RECIST 1.1), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). Results: 158 patients were recruited from 14 UK hospitals (79 in each arm). Median age (range) was 56(34-81) in the cabazitaxel arm and 61(34-79) in the paclitaxel arm. 61% of patients were performance status 0. Median time on treatment was 15 weeks for both arms, but more patients on paclitaxel had a treatment delay (61% vs 39%) or dose reduction (37% vs 24%). Comparing cabazitaxel to paclitaxel after 146 PFS events, median PFS was 6.7 vs 5.8 months (HR 0.84;95%CI 0.60-1.18, P = 0.3). There was no difference in OS, median 19.3 vs 20.0 months (HR 0.94;95%CI 0.63-1.40, P = 0.7), ORR (42% vs 37%) or TTR (HR 1.09;95%CI 0.68- 1.74, P = 0.7). Grade ≥3 adverse events occurred in 42% of patients on cabazitaxel and 48% on paclitaxel. Diarrhoea, febrile neutropenia and nausea were the most common grade ≥3 events in the cabazitaxel arm with rates of 11%, 11% and 10% respectively compared to 1%, 1% and 0% in the paclitaxel arm. In the paclitaxel arm the top grade ≥3 events were lung infection and peripheral neuropathy, 6% and 5% respectively compared to 2.5% and 0% in the cabazitaxel arm. Peripheral neuropathy of any grade was reported by 55% of patients treated with paclitaxel vs 17% on cabazitaxel. Alopecia occurred in 41% of patients on paclitaxel compared to 27% on cabazitaxel. Adverse events leading to discontinuation were more frequent with paclitaxel (22%) than cabazitaxel (14%). Over the course of treatment, mean EQ5D single index utility score (+0.05;95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7;95%CI 3.1-12.3, P = 0.001) were higher in the cabazitaxel arm compared to paclitaxel suggestive of better QoL on Cabazitaxel. Conclusions: 3 weekly cabazitaxel as first line chemotherapy in HER2 negative MBC does not significantly improve PFS compared to weekly paclitaxel, though it has a lower risk of peripheral neuropathy with better patient reported overall health outcomes. Cabazitaxel is safe and well tolerated for MBC and requires fewer hospital visits, an important consideration in the COVID pandemic and beyond.
ABSTRACT
Antibody test is used in seroprevalence surveys for Coronavirus Disease-2019 (COVID-19). Apart from estimating the proportion of population infected, they can help in drawing plenty of inferences about the extent, progress and course of the pandemic. They can potentially be helpful in planning and prioritising vaccine distribution by providing a broad overview into proportion of population immune to COVID-19 in a geographic area and also help in understanding the pockets of high or low seroprevalence. This review was conducted with an aim of compiling an updated and comprehensive information about the seroprevalence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody in various pockets of India in the year 2020, and thus to understand the current pandemic situation in the country. A total of 35 studies were identified through all resources and detailed review was carried out based on these studies. Additionally, indicators were devised to understand and compare the results. Results were further classified into states/Union Territories (UTs), districts, Sub-district regions. The study findings show that the anti SARS-CoV-2 antibodies seroprevalence estimates vary across different regions (states/UTs, districts, sub district regions) of India and can increase or in some instances decrease over the course of time. The study concludes by asserting the need for repeated seroprevalence surveys as well as follow-up studies for current pandemic surveillance.
ABSTRACT
Introduction Experience regarding course and outcome of Covid-19 infection in heart transplant recipients is limited. Case fatality rate of 25% of covid-19 infection in adult recipients of heart transplant and mild and self-limited disease in young heart transplant patients have been reported in small case series. We describe a case where a 13 year old patient contracted covid-19 infection on 7th post-operative day after undergoing heart transplant and was subsequently discharged from hospital uneventfully. Case Report A 13 year old boy, with dilated cardiomyopathy underwent orthotopic heart transplant surgery. In the immediate pre-operative period, the real-time polymerase chain reaction (RTPCR) of nasopharyngeal swabs of both the recipient and the brain-dead organ donor were negative for severe acute respiratory syndrome coronavirus type 2 (SARS CoV 2). The intraoperative and immediate postoperative periods were uneventful. The recipient got weaned off from mechanical ventilation on the 1st postoperative day and O2 support was weaned off on 4th postoperative day. He was put on immunosuppressive regimen consisting of mycophenolate mofetil, tacrolimus and prednisone. On 7th postoperative day, he complained of fever, sore throat and dry cough. Nasopharyngeal swab for RTPCR was sent. It reported positive for SARS CoV 2. He was shifted to isolation facility. He maintained more than 94% saturation on pulse oximetry in room air. Immunosuppressive regimen was continued. He was administered 5-day course of remdesivir. Inotropic support was weaned off on 10th postoperative day. On serial bedside echocardiography, the allograft function was found to be normal throughout. He was kept on prophylactic antimicrobial, antifungal and anti-cytomegaloviral therapy and on prophylactic dose of low molecular weight heparin. There was initial rise in neutrophil lymphocyte ratio (17), C reactive protein (58 mg/l), ferritin (871 ng/ml), D-dimer (1904 ng/ml), Troponin T (227 pg/ml) levels, which gradually came down to within normal limits. He was discharged on 38th postoperative day to a home isolation facility as his RTPCR for SARS CoV 2 was still positive, although he remained completely asymptomatic for the last 21 days. Summary The course of Covid-19 infection in the immediate post-transplant period of this young heart transplant recipient was largely uneventful.