The Impact of COVID-19 on the Delivery of Systemic Anti-Cancer Treatment at Guy's Cancer Centre.

BACKGROUND: This study aimed to assess the outcome of cancer patients undergoing systemic anti-cancer treatment (SACT) at our centre to help inform future clinical decision-making around SACT during the COVID-19 pandemic. METHODS: Patients receiving at least one episode of SACT for solid tumours at Guy's Cancer Centre between 1 March and 31 May 2020 and the same period in 2019 were included in the study. Data were collected on demographics, tumour type/stage, treatment type (chemotherapy, immunotherapy, biological-targeted) and SARS-CoV2 infection. RESULTS: A total of 2120 patients received SACT in 2020, compared to 2449 in 2019 (13% decrease). From 2019 to 2020, there was an increase in stage IV disease (62% vs. 72%), decrease in chemotherapy (42% vs. 34%), increase in immunotherapy (6% vs. 10%), but similar rates of biologically targeted treatments (37% vs. 38%). There was a significant increase in 1st and 2nd line treatments in 2020 (68% vs. 81%; p < 0.0001) and reduction in 3rd and subsequent lines (26% vs. 15%; p = 0.004) compared to 2019. Of the 2020 cohort, 2% patients developed SARS-CoV2 infections. CONCLUSIONS: These real-world data from a tertiary Cancer Centre suggest that despite the challenges faced due to the COVID-19 pandemic, SACT was able to be continued without any significant effects on the mortality of solid-tumour patients. There was a low rate (2%) of SARS-CoV-2 infection which is comparable to the 1.4%-point prevalence in our total cancer population.

Risk of COVID-19 death in cancer patients: an analysis from Guy's Cancer Centre and King's College Hospital in London.

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.

COVID-19 Risk Factors for Cancer Patients: A First Report with Comparator Data from COVID-19 Negative Cancer Patients.

Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1st March and 31st July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.

Factors Affecting COVID-19 Outcomes in Cancer Patients: A First Report From Guy's Cancer Center in London.

Background: There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with a severe case of the disease. An initial cancer diagnosis >24 months 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)], gastro-intestinal symptoms [7.38 (2.71-20.16)], or higher levels of C-reactive protein [9.43 (0.73-121.12)] were linked with greater COVID-19 severity. During a median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Being of Asian ethnicity [3.73 (1.28-10.91)], receiving palliative treatment [5.74 (1.15-28.79)], having an initial cancer diagnosis >24 months 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 positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin [0.04 (0.01-0.04)]. Conclusions: A longer-established diagnosis of cancer was associated with increased severity of infection as well as COVID-19 death, possibly reflecting the effects a more advanced malignant disease has on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients.

Trabectedin for advanced soft tissue sarcomas: a single institution experience.

BACKGROUND: We retrospectively analyzed data from patients who had been treated with trabectedin at our institution between April 2009 and August 2011. PATIENTS & METHODS: Data from 25 patients with recurrent soft tissue sarcoma (leiomyosarcoma: n = 8; liposarcoma: n = 5) were used to assess the efficacy and safety of trabectedin 1.5 mg/m(2) given every 3 weeks. RESULTS: Most patients (n = 14) had been heavily pretreated with ≥ 2 previous chemotherapy lines. Eight (32%) patients achieved a partial response according to dimensional and tumor density changes, and seven (28%) patients had stable disease for ≥ 3 months (clinical benefit rate = 60%; n = 15). Median progression-free survival was 6.4 months and overall survival 19.3 months. Common adverse events were fatigue, nausea, anemia and transient transaminase increases. CONCLUSION: Treatment with trabectedin is effective and well tolerated in heavily pretreated soft tissue sarcoma patients. Tapering dexamethasone courses and switching trabectedin administration to an every 4 weeks schedule effectively dealt with persistent fatigue without compromising effectiveness.

Adjuvant therapy in renal cell carcinoma-past, present, and future.

To date, no effective adjuvant treatment for renal cell carcinoma (RCC) has been described, but research in this area is important since the 5-year relapse rate for intermediate- and high-risk early-stage RCC is 30%-40%. Metastatic RCC can be treated successfully with immune therapy and targeted therapy. Adjuvant trials with immune therapy have been conducted, but they reported no benefit in disease-free survival, and clinical trials with targeted agents have not yet reported results. Further advances in our understanding of the molecular pathogenesis of RCC will identify additional potential targets for adjuvant treatment trials. Future challenges will consequently include target identification, as well as trial design to answer multiple trial questions concurrently, comprehensively, and economically. We review the past efforts, summarize the current adjuvant clinical trial landscape, and consider the challenges in adjuvant trials for RCC. Additionally, we identify potential future adjuvant trial treatments and propose an alternative design for future adjuvant clinical trials.

Regorafenib (BAY 73-4506): stromal and oncogenic multikinase inhibitor with potential activity in renal cell carcinoma.

The introduction of targeted therapies, specifically those that target the VEGF receptor (VEGFR), PDGF receptor (PDGFR) and the mTOR pathways, has significantly changed the approach to patients with unresectable renal cell cancer (RCC). However, drug resistance develops through bypassing of targeted pathways. Regorafenib (BAY 73-4506) is a novel bi-aryl urea compound that has potential anti-tumour activity in RCC, as along with targeting VEGF and PDGF receptors, it targets additional kinases associated with alternative pathways of angiogenesis and resistance to VEGF-targeted drugs. Based on a phase II clinical trial, the efficacy outcome of regorafenib in the first-line setting of unresectable RCC appears comparable that of other targeted first-line drugs. However, testing regorafenib in standard phase III trials seems inappropriate in view of its toxic effects. Further assessment of regorafenib should exploit the drug's ability to inhibit mechanisms of escape from anti-angiogenic treatment through biomarker-driven clinical trials.

The role of angiogenesis inhibitors in the management of melanoma.

Metastatic melanoma has a very poor prognosis and systemic therapies - both cytotoxic and biological - have not improved outcome in this disease so far. For this reason, novel therapeutic strategies are urgently required. Angiogenesis represents a relevant process to modulate in melanoma, as pro-angiogenic ligands and their receptors are overexpressed and have been found to correlate with disease progression and prognosis. The angiogenic axis may be targeted at many different levels, which are still being defined. This article presents an overview of the importance of angiogenesis in melanoma and draws attention to some of the key molecules that are currently being targeted rationally within clinical studies. We discuss a number of anti-angiogenic and anti-vascular agents and their mechanisms of action. An overview of the efficacy and toxicity of these treatments in clinical trials performed so far in melanoma is presented and future directions for anti-angiogenic strategies in melanoma are considered.

Options for the treatment of gemcitabine-resistant advanced pancreatic cancer.

CONTEXT: Pancreatic cancer is noteworthy in that the number of patients dying from the disease is roughly equal to the number diagnosed. For more than a decade, gemcitabine has constituted the standard of care for the palliative treatment of the majority of patients who present with metastatic or relapsed disease, although the survival gains are limited. Despite a median survival of less than 6 months, there is a significant proportion of advanced pancreatic cancer patients who progress on gemcitabine that remains fit and these patients are candidates for second-line treatment. METHODS: The OVID MEDLINE database was searched from 1950 to present using the MeSH terms "pancreatic neoplasms", "drug treatment" and "gemcitabine". After excluding non-relevant results, 31 published studies were identified. These results were supplemented by searching the last three (2007-2009) American Society of Clinical Oncology (ASCO) Proceedings of Annual Meetings for studies published only in abstract form and reviewing reference lists of published articles. RESULTS AND DISCUSSION: The evidence for second line treatments of metastatic pancreatic cancer consists mostly of single arm, small phase II studies. Oxaliplatin-fluoropyrimidine combinations appear promising and have shown increased survival compared to best supportive care. As the molecular pathways governing pancreatic cancer are unravelled, novel targeted therapies may offer the greatest promise for this disease either given alone, combined with one another, or with cytotoxic agents. The need for further, collaborative research is emphasised.