ABSTRACT
Background: In December 2020, there were queries amongst clinicians, and a lack of consensus on the best management of SACT patients receiving COVID-19 vaccination. As novel vaccines, there was no available information in this patient cohort and an urgent need to provide a consistent approach. A national group of multi-disciplinary SACT clinicians worked with the UK Chemotherapy Board (UKCB), based on initial guidelines from Guys & St Thomas NHS Foundation Trust, to produce clear information. Aim and objectives: To produce and assess the utility of an evidence-based document to support clinicians in the safe and effective delivery of COVID-19 vaccines for SACT patients. Methodology: A literature review of published data for other vaccinations in combination with chemotherapy was undertaken to determine existing evidence available to guide empirical decisions about the scheduling of the coronavirus vaccines with chemotherapy. PubMed was searched for Randomised Controlled Trials published in English, with an available with MESH Topics: “influenza vaccine” or “pneumococcal vaccine” and “drug therapy” and a subject area of “cancer”. Given the urgency and limited information available, a virtual group was formed to develop answers using extrapolated data and agree a consensus document that was consistent with available guidance from the Joint Committee Vaccination Immunisation (JCVI), Medicines Health Regulatory Agency (MHRA) & Summary of Product Characteristics (SPC). This was peer reviewed by multi-disciplinary stakeholders from across the SACT pathway, the UKCB and COVID-19 vaccination groups. An online survey was designed using quantitative methodology with a free text option to obtain qualitative feedback. To maximise responses, the approach was to keep the survey simple and quick. The survey was circulated via email through the UKCB, NHS England Cancer Commissioning Pharmacists and social media. Results: From the literature review, 36 publications were identified, 21 were subsequently excluded for not describing co-administration with SACT, 11 publications were excluded for not comparing the scheduling of vaccine relative to cancer treatment. Of the four remaining publications, three described antibody titres to influenza vaccine and one described the same for 13-valent pneumoccocal vaccine following administration of the vaccine at different time points during the chemotherapy cycle. These were considered during development of the Frequently Asked Questions (FAQs). Of 239 healthcare professionals who responded to the survey, (142 Pharmacists;60 Doctors;22 Nurses;15 were pharmacy technicians/radiotherapists) 215 were from secondary care and 9 were non-UK respondents. 60% respondents (142/239) reported being aware of the Guidance 132 respondents reported they had referred to the document and 120/132 (91%) reported finding the guidance helpful/very helpful. (10 did not respond) Conclusion: The survey has demonstrated that this FAQ document has been a valuable resource to many clinicians treating patients within the UK and world-wide. As the landscape for COVID-19 vaccination evolves, feedback suggested future versions could be disseminated more widely in a timely way. Building on our learning of COVID-19 vaccination for SACT patients, the document will continue to be updated as more data emerges. We encourage the UKCB to consider how best it can disseminate guidance to a wider audience.
ABSTRACT
Introduction: Cancer patients have been considered a high-risk population in the COVID-19 pandemic. We previously investigated risk of COVID-19 death in COVID-19 positive cancer patients during a median follow-up of 134 days, and identified the following risk factors: male sex, age >60 years, Asian ethnicity, hematological cancer type, cancer diagnosis for >2.5 years, patients presenting with fever or dyspnea, and high levels of ferritin and C-reactive protein (CRP). Here, we further investigate which factors are associated with a COVID-19 related death within 7 days of diagnosis. Methods: Using data from Guy's Cancer Centre and one of its partner trusts (King's College Hospital), we included 306 cancer patients with a confirmed COVID-19 diagnosis (February 29th-July 31st 2020). 72 patients had a COVID-19 related death (24%) of whom 35 died within 7 days (50%). Cox proportional hazards regression was used to identify which factors were associated with a COVID-19 related death <7 days of diagnosis. Results: Of the 72 cancer patients who had a COVID-19 related death, the mean age was 72 years (Standard Deviation (SD) 14). A total of 53 (74%) patients were men. 37 (52%) had a hematological cancer type, 47 (65%) had stage IV cancer, and 42 (58%) had been diagnosed with cancer more than 24 months before COVID-19 related death. In the group of patients who died within 7 days of diagnosis (n= 35), mean age was 73 years (SD 13.96), 24 (68%) were men, 20 (57%) had a hematological cancer type, 26 (74%) had stage IV cancer, and 24 (68%) had been diagnosed with cancer >24 months before COVID-19 diagnosis. Factors associated with COVID-19 related death <7 days of diagnosis were: hematological cancer (Hazard Ratio (HR): 2.74 (95% Confidence Interval (CI): 1.21-6.22)), 2-5 yrs since cancer diagnosis (HR: 4.81 (95%CI: 1.47-15.69)), and >5 yrs since cancer diagnosis (HR: 4.41 (95%CI: 1.38-14.06)). Additionally, patients who presented with dyspnea had increased risk of COVID-19 related death <7 days compared to asymptomatic patients (HR: 5.25 (95%CI 2.14-12.89)). CRP levels in the third tercile (146-528 mg/L) as compared to the first were also associated with increased risk of an early death due to COVID-19. Conclusion: From all the factors identified in our previous COVID-19 related death analysis, only hematological cancer type, a longer-established cancer diagnosis (2-5 years and more than 5 years), dyspnea at time of diagnosis and high levels of CRP were indicative of an early COVID-19 related death (within 7 days of diagnosis) in cancer patients.
ABSTRACT
Background: To understand the impact of the COVID-19 pandemic on National Health Services (NHS) cancer service delivery, care and patients, we examined the impact of changes in cancer service delivery, treatment intensity and delay by evaluating oncological outcomes of genitourinary (GU) cancer patients receiving systemic anticancer treatment (SACT) during 1st March and 8th July 2020. Methods: We used data from patients with GU cancers (i.e. prostate, urothelial, kidney and testicular) treated with SACT at Guy's Cancer Centre during the first wave of the COVID-19 pandemic in the UK: demographics (sex, age, ethnicity, ECOG performance status (PS), comorbidities, smoking history, socio-economic status (SES)) and disease characteristics (stage, treatment type and setting, lines of treatment), as well as results from SARS-CoV-2 PCR testing. Classification of COVID-19 severity was based on the World Health Organisation (WHO) guidelines. Results: A total of 457 GU cancer patients received SACT during the study period: 68% prostate cancer, 23% renal cancer, 7% urothelial cancer, 2% testicular cancer. Mean age was 69 years (SD: 11.2). 91% were males, 82% were classified as low SES and out of the 291 patients we had ethnicity data on 199 (68%) were White British. The majority of patients had a PS of 1 and 95% of all patients had stage IV disease and hence received palliative SACT, with 58% being in the second line setting. Half of the patients received hormone therapy, 17% received chemotherapy, 20% received targeted therapy, 13% received immunotherapy (IO) and 1% received combination IO and targeted treatment. Only 5 (1%) patients tested SARS-CoV-2 positive: 2 had prostate cancer, 2 renal and 1 bladder cancer. Mean age was 66 years (SD: 5.6). They were all male, 2 White British, 1 Black African and 2 of unknown ethnicity and were all classified as low SES. Average PS was 2. Of these 5 patients 3 had at least two comorbidities (i.ehypertension, diabetes mellitus, renal impairment, frailty) and were receiving multiple medications. All had stage IV disease and received palliative SACT. 3 were on hormone therapy alone and 2 on chemotherapy. 2 of the patients presented symptoms within less than 7 days from PCR diagnosis, 1 within 7 to 14 days and 1 after 14 days. All 5 COVID-19 positive patients required hospitalization, 4 suffered severe pneumonia, 1 died from COVID-19 and 2 died from cancer related causes. In comparison, the mortality rate for the COVID-19 negative patients was 3.3%. Conclusion: Despite the impact of COVID-19 in health provision, a large number of our GU patients at Guy's Cancer Centre safely received SACT. Our results suggest that the continuation of SACT during the COVID-19 pandemic did not increase the risk of COVID-19 in our patient cohort (SARS-CoV-2 infection rate: 1%). Of note, the infection rate was lower than observed in a similar study in our centre for gastrointestinal cancer patients (SARS-CoV-2 infection rate: 3.4%). In light of the above, decisions against SACT or SACT intensity should carefully be evaluated.
ABSTRACT
Background: The Coronavirus disease 2019 (COVID-19) pandemic continues to have a significant impact on the treatment of cancer patients. Understanding the clinical course, potential risk factors for severe infection and excess mortality, is essential to improve patient outcomes. We previously presented preliminary results from 156 SARS-CoV-2 positive cancer patients from Guy's Cancer Center, which suggested that increased COVID-19 mortality was associated with a diagnosis of cancer for over 2 years, Asian ethnicity and being on palliative treatment. Herein, we present an updated analysis using data from Guy's Cancer Centre and a partner Hospital Trust (King's College Hospital), with an increased number of patients and an extended follow up. Methods: We performed an analysis of all cancer patients who had a positive RT-PCR nasal/throat swab for SARS-CoV-2 infection at our Centers between 29th February and 31st July 2020. Associations between patients' demographics, clinical characteristics, and laboratory investigations with COVID-19 severity and mortality, were assessed using Logistic regression and Cox proportional hazards models. Results: 306 SARS-CoV-2 positive cancer patients were included in the analysis with a median follow up of 134 days (IQR 32-156). 184 (60%) were male and 217 (71%) were aged over 60 (mean age: 66). The most common malignancies were haematological (38%) and urological-gynaecological (20%). 218 (71%) had mild/moderate COVID-19 and 88 (29%) had severe disease. The overall COVID-related mortality rate was 24%;19% in solid and 32% in haematological cancers. Male sex [OR: 1.84 (95%CI:1.08-3.13)], Asian ethnicity [3.86 (1.20-12.36)], haematological cancer type [2.16 (1.18-3.95)], being diagnosed with cancer for 2-5 years [3.74 (1.80-7.78)] or ≥5 years [3.06 (1.50-6.26)] and a ferritin > 1964 mcg/l [54.92 (5.90-511.33)] were all associated with a risk of developing severe COVID-19 disease. Similarly, male sex [HR:1.97 (95%CI:1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer type [2.03 (1.16-3.56)] as well as a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years [2.13 (1.06-4.27)] and a ferritin > 1964 mcg/l [16.11 (3.81-68.17)] were associated with an increased risk of death from COVID-19. Age >60 [2.14 (1.15-3.98)] and a raised CRP [4.10 (1.66-10.10)] were also associated with COVID-19 death. An inverse relationship was observed between a raised albumin and COVID-19 related death [0.12 (0.03- 0.51)]. Performance status and treatment paradigm were not associated with COVID-19 severity or mortality. Conclusions: This study further substantiates the evidence for an increased risk of severe COVID-19 infection and mortality for male and Asian patients with cancer, and those with haematological malignancies or with a diagnosis of cancer for over 2 years. These risk factors should be taken into account when making clinical decisions for cancer patients during the pandemic.
ABSTRACT
Background: The provision of cancer services has been strongly impacted by the outbreak of SARS-CoV-2. Our Cancer Centre in South-East London treats about 8,800 patients annually (incl. 4,500 new diagnoses) and is one of the largest Comprehensive Cancer Centres in the UK. The first COVID-19 positive cancer patient was reported on 29 Feb 2020. Whilst we are dealing with the second wave of COVID-19, it is important to further evaluate safety of cancer treatments whilst balancing risks of COVID-19 infection and complications. Methods: Using descriptive statistics, we report on the patient/tumour characteristics as well as short-term clinical outcomes of those patients undergoing radical treatment (i.e. systemic anticancer treatment (SACT), surgery, or radiotherapy (RT)) for their cancer during the first wave as to help establish the clinical guidelines for the management of cancer patients in a SARS-CoV-2 epidemic. Results: Between March-July 2020, 1,553 patients underwent surgery, 1,125 received SACT, and 814 had RT. Compared to the same period in 2019, there was a decrease of 28% for surgery, 15% for SACT, and 10% for radiotherapy. Whilst surgery was performed on more male patients (58%), more women received SACT (75%) and RT (58%). The age distribution was similar between treatment arms, with the majority of patients aged 50 to 80 years. The most common tumour types were breast (21%), thoracic (20%), and urological (29%) for surgical treatment;breast (49%), gastrointestinal (18%), and gynaecological (10%) for SACT;and breast (40%), urology (25%), and head & neck (11%) for RT. Within SACT, 36% received combination therapy, 35% received systemic chemotherapy, 23% targeted therapy, 5% immunotherapy, and 2% biological therapy. In terms of oncological outcomes, outcomes were similar to pre-COVID-19 times;with 6 deaths at 30 days (<1%) for surgical patients and 36 readmissions (2%), 10 deaths (<1%) for SACT patients, and 52% of RT delivered with radical intent (which was the same in 2019). The COVID-19 infection rates for our patients were very low: 12 patients were positive pre-surgery (1%), 7 post-surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19 related deaths were registered for the surgical, SACT and RT patients. Conclusion: Whilst there was a decline in overall radical treatment, likely due to a delay in cancer diagnoses, those who did undergo their treatment were treated in a safe COVID-19 managed environment. Our findings highlight that cancer patients should have the confidence to attend hospitals and be reassured of the safety measurements taken.
ABSTRACT
Background: Early reports in the COVID-19 pandemic suggested higher mortality for cancer patients. The impact of potentially immunosuppressive systemic anti-cancer treatments (SACT) was unknown. This study analysed the delivery of SACT for patients with solid malignancies during the COVID-19 outbreak in 2020 compared to the same period in 2019 to inform future clinical decision-making. Methods: All patients receiving at least one SACT at Guy's comprehensive Cancer Centre during the COVID-19 outbreak for solid tumours (1st March- 31st May 2020) were compared to the same period in 2019. SARS-CoV2 infection was by positive RT-PCR test. Data collected: demographics, tumour type/stage and treatment (chemotherapy, immunotherapy (IO), biological-targeted (BT)). Results: 2125 patients received SACT in 2020, compared to 2450 in 2019 (13% decrease). Demographics were comparable with mean age of 62. 56% females in 2020 vs 54% in 2019, 85% vs 83% in the low socio-economic category, 63% vs 73% PS 0-1;30% vs 29% uro-gynaecological, 27% vs 24% breast and 20% vs 23% GI tumours. In 2020 compared to 2019, there was an increase in metastatic disease (71% vs 62%), decrease in CT (34% vs 42%), increase in IO (10% vs 6%), but similar rates of BT treatments (38% vs 37%). Treatment paradigms were similar in 2020 and 2019: neo/adjuvant (28% vs 29%), radical (4% vs 5%) and palliative (69% vs 67%). Earlier palliative treatments were prioritised in 2020 with significant increase in treatments in 1st-2nd line (72% vs 67%;p=0.02) and reduction in > 3rd line (12% vs 27%;p<0.05). 42 of 2125 patients (2%) developed SARS-CoV2 infections;38% GI, 26% breast with 69% on CT. Of 42 patients with COVID-19, 24 (57%) had severe infections and 6 (14%) resulted in COVID-related death. Conclusions: These data suggest that SACT does not put solid tumour patients at much a higher additional risk from COVID-19. Despite a 13% decline in treatment rates, radical and early palliative treatment were prioritised. There was a low frequency (2%) of SARS-CoV-2 infection;comparable to the 1.4% point prevalence rate in our cancer population. However, this was during national lockdown with limited COVID-19 testing. The next steps are to evaluate the impact of new variant strains and COVID vaccination programme. Legal entity responsible for the study: Guy's Real-World Evidence. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: Pembrolizumab (pembro) is a PD-1 inhibitor indicated for the treatment (tx) of a several malignancies. Most clinical trials used a 3-weekly tx (Q3W) but a 6-weekly 400mg regimen (Q6W) is now approved, based on pharmacokinetic data, also supported by the KEYNOTE-555 trial. The real world tolerability of the Q6W remains unknown. The COVID-19 pandemic led to rapid adoption of the Q6W tx, usually in patients (pts) previously receiving Q3W tx, as it facilitates less hospital visits. We report the toxicity profile of pts treated with Q6W pembro and the comparison of the preceding Q3W tx. Methods: We retrospectively analysed adverse events for non-small cell lung cancer (NSCLC), urothelial cancer (UC) and melanoma pts, who received at least 1 cycle of Q6W pembro. Pts that received pembro in combination tx were excluded. Previous Q3W monotherapy was permitted. Toxicity was graded as per CTCAE v5.0. Results: We included 94 pts (melanoma=39, NSCLC=38, UC=17). Median number of Q6W cycles received was 3 (range 1-6). 71% received the Q3W regimen (median 7 cycles, range 1-32) prior to switching to Q6W. New toxicity of any severity was recorded in 52% (49/94) during Q6W versus 70% (47/67) during Q3W tx. G 3/4 toxicities occurred in 15% (15) during Q6W versus 0% during previous Q3W tx. Of the 27 who started de novo with Q6W, 4 (15%) developed G 3/4 toxicities. G 3/4 toxicities were: GI (4% [colitis = 2, gastritis =1, oral lichen planus = 1]), nephritis (3%), arthralgia (2%), skin (2%), myositis/CK rise (2%), anaemia (1%), myocarditis (1%). Steroids for management of toxicity were initiated in 22% (21) pts, including 8 with G2 toxicity. Three (3%) pts switched back to Q3W administration. None of them received Q6W again. In total 9% of pts in Q6W discontinued tx due to toxicity. Conclusions: In our cohort of pts, the majority were previously treated with the Q3W regimen without significant toxicity. Switch to Q6W or de novo Q6W pembro led to a 15% rate of G 3/4 toxicity and 9% discontinuation rate. In pts pre-treated with Q3W, we cannot distinguish whether this was due to cumulative toxicity or due to switch to Q6W. More studies are required to ascertain the safety of the Q6W schedule. In the COVID-19 context, any Q6W toxicity concern should be weighed against the advantages of fewer hospital visits. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: The provision of cancer services has been strongly impacted by the outbreak of SARS-CoV-2. Our Cancer Centre in South-East London treats approximately 8,800 patients annually and is one of the largest Comprehensive Cancer Centres in the UK. When dealing with the second wave of COVID-19, it is important to further evaluate the safety of cancer treatments whilst balancing the risks of COVID-19 infection and complications. Here, we report on the patient/tumour characteristics of those patients undergoing SACT for a urological cancer diagnosis during the first wave, so as to help establish clinical guidelines for the management of these patients in a SARS-CoV-2 epidemic. Methods: All urological cancer patients receiving at least one SACT between 1st March- 31st May 2020 (COVID-19 period) were compared to the same timeframe in 2019. SARSCoV2 infection was defined as a positive RT-PCR test;patients with symptoms or radiological changes alone were excluded. As part of Guy's Cancer Cohort, we collected information on demographics, and cancer type, stage, and treatment. Results: A total of 455 patients (305 prostate, 102 renal, 38 bladder, and 10 testicular) received SACT in 2020 as compared to 535 (353 prostate, 129 renal, 37 bladder, and 15 testicular) in 2019 (15% overall decline). Patient characteristics in terms of demographics were fairly comparable, with 10% female patients in 2019 and 9% in 2020;49% aged 70+ vs 45%;and 77% in the low socioeconomic category vs 78%. There was an increase in patients with stage 4 (89% vs 95% in 2020) and a slight change in distribution of SACT types (2019 vs 2020): chemotherapy (18% vs 14%), immunotherapy (7% vs 10%), biological or targeted (63% vs 66%), combination of biological/targeted (6% vs 5%), other combinations (5% vs 5%). The proportion of SACT delivered as part of radical treatment declined from 3% to 0.2% in 2020. A total of 5 patients (1%) developed COVID-19 (2 prostate, 2 renal, and 1 bladder). All were male and aged 60+;three had 2+ comorbidities. One patient was on immunotherapy and four on biological or targeted treatment. Four patients had severe pneumonia and one died of their COVID-19 (bladder cancer). Conclusions: Whilst there was a decline of number of patients receiving SACT during COVID-19, we were still able to provide a safe high-quality urological cancer SACT pathway during the peak of the COVID-19 pandemic, with very few COVID-19 positive patients. In a next step we will evaluate oncological outcomes at 6 months follow-up.
ABSTRACT
Background: Current precautionary management decisions being made for cancer patients are based onassumptions supported by limited evidence, based on small case series from China and Italy and larger series fromNew York and a recent consortium of 900 patients from over 85 hospitals in the USA, Canada, and Spain. Hence, there is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 dueto the lack of large studies. Methods: We used data from a single large UK Cancer Centre to assess demographic/clinical characteristics of 156cancer patients with a confirmed COVID-19 diagnosis between 29 February-12 May 2020. Logistic/Cox proportionalhazards models were used to identify which demographic and/or clinical characteristics were associated withCOVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with severe disease. Initial diagnosis ofcancer >24m before COVID-19 (OR:1.74 (95%CI: 0.71-4.26)), presenting with fever (6.21 (1.76-21.99)), dyspnea(2.60 (1.00-6.76)), gastrointestinal symptoms (7.38 (2.71-20.16)), or higher levels of CRP (9.43 (0.73-121.12)) werelinked with greater COVID-19 severity. During median follow-up of 47d, 34 patients had died of COVID-19 (22%).Asian ethnicity (3.73 (1.28-10.91), palliative treatment (5.74 (1.15-28.79), initial diagnosis of cancer >24m before(2.14 (1.04-4.44), dyspnea (4.94 (1.99-12.25), and increased CRP levels (10.35 (1.05-52.21)) were positivelyassociated with COVID-19 death. An inverse association was observed with increased levels of albumin (0.04 (0.01-0.04). Conclusions: Our analysis of one of the largest single-center series of COVID-19-positive cancer patients to dateconfirms a similar distribution of age, sex, and comorbidities as reported for other populations. With respect tocancer-specific observations, patients who have lived longer with their cancer were found to be more susceptible toa greater infection severity, possibly reflecting the effect of more advanced malignant disease, as almost half of thesevere cohort were on third-line metastatic treatment, or the impact of this infection. The latter was also found to beassociated with COVID-19 death in cancer patients, as were Asian ethnicity and palliative treatment. Furthervalidation will be provided from other large case series, as well as from those including longer follow-up, to providemore definite guidance for oncologic care.