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Background: Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer., Methods: In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission., Findings: From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 [95% CI 6·56-10·02]; p<0·0001), being male (1·67 [1·19-2·34]; p=0·003), and the presence of other comorbidities such as hypertension (1·95 [1·36-2·80]; p<0·001) and cardiovascular disease (2·32 [1·47-3·64]). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 [0·81-1·72]; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks., Interpretation: Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment., Funding: University of Birmingham, University of Oxford., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Small cell transformation is a well-recognized mechanism of resistance to EGFR-TKI therapy in EGFR-mutant NSCLC, yet it remains a poorly-described phenomenon in ALK-rearranged NSCLC., Material and Methods: Chart and literature review., Results: We report a case of a patient with ALK-rearranged lung cancer progressing on three-lines of ALK-targeted therapies, with development of acquired resistance to lorlatinib, with both transformation to a neuroendocrine carcinoma, and acquisition of ALK 1196 M., Conclusions: Given the inevitable development of resistance in ALK + NSCLC, if feasible, re-biopsy on progression should be standard over liquid biopsy. Neuroendocrine carcinoma transformation remains an important mechanism of acquired resistance to lorlatinib., (Copyright © 2019 Elsevier B.V. All rights reserved.)

There are no published data on the costs associated with investigating and managing toxicity from ipilimumab treatment in patients with metastatic melanoma. Patients treated with ipilimumab at The Royal Marsden Hospital between 1 September 2010 and 1 April 2013 were identified. Data on demographics, investigations and survival outcomes were collected. Patients with grade 3 or higher immune-related adverse events were identified, and costs of investigating and managing toxicities in them were calculated on the basis of standard National Health Service tariffs. Out of the 110 patients, 29 experienced grade 3/4 immune-related adverse events. The total cost of investigating and managing these patients was £140,680, or a median cost of £2860 per patient. Patients experiencing grade 3/4 toxicities had 1-, 2- and 3-year survival rates of 79, 59 and 46%, compared with 24, 17 and 15% in the group that did not experience significant toxicity (P<0.0005). The most common treatment-related toxicity identified was colitis. Two patients died from complications associated with ipilimumab colitis. The cost of ipilimumab toxicity is marginal in comparison with the total treatment cost. Patients treated with ipilimumab who develop significant toxicity have a higher than expected 1-, 2- and 3-year survival.

Introduction: Aberrant activation of RAF signalling is a frequent finding in human cancers. BRAF is the only RAF family member that is commonly mutated, whilst CRAF and ARAF play important roles in the signal transduction from mutant RAS. BRAF-specific inhibitors have been more effective in the treatment of BRAF-mutant melanoma than BRAF-mutant thyroid and colorectal cancers., Areas Covered: The review summarises the experience with RAF kinase inhibitors, including efficacy, modes of acquired resistance, and the mechanism behind the progression of pre-malignant RAS-mutant lesions observed with RAF kinase inhibitors. The authors review all the completed and ongoing Phase I or II clinical trials of RAF kinase inhibitors and discuss in detail the rationale behind the combinatorial approaches., Expert Opinion: The success of RAF kinase inhibitors has demonstrated the necessity of genotype-driven treatment selection for cancer patients. The spectrum of responses in different tumour types is explained by feedback events that are determined by cell lineage. Dissection of these events and the mechanisms of acquired resistance will determine the appropriate combination therapies. Ongoing characterisation of RAS-MAPK regulation in malignant cells may aid the development of novel agents that have greater potency for the inhibition of activated RAF kinase, and lesser propensity for promotion of RAS-mutant tumours.

Background: Recent UK clinical guidance advises against continuing trastuzumab (T) beyond disease progression (PD) in the absence of brain metastases in patients with HER-2 positive (+ve) advanced breast cancer .We have retrospectively evaluated the outcome of patients with HER-2+ve locally advanced (LA) or metastatic breast cancer (MBC) who continued T beyond PD, treated in our unit., Methods: All HER-2+ve patients on our prospectively maintained database with LA or MBC who received T beyond PD after adjuvant or one line of T for advanced disease were assessed for response and outcome. From the timepoint of T continuation beyond PD, we calculated the overall disease control rate, time to progression (TTP), and overall survival (OS)., Results: One hundred and fourteen patients with HER-2+ve LA or MBC treated with T beyond PD were identified. The main site of disease was visceral in 84 (74%) patients. Seventy-six (66%) had one line of chemotherapy before continuation of T beyond PD and 21 (19%) had two or more. Post-progression, 66 (58%) received T combined with chemotherapy. Of the 93 (82%) patients with documented clinical or radiological response evaluation, 67 (59%) were considered as having stable disease or better. The median TTP was 24 weeks (95% CI: 21-28) and the median OS was 19 months (95% CI: 12-24)., Conclusion: Our results from an unselected group of patients provide additional evidence that continuation of T beyond PD is of clinical benefit.