Targeting FGFR inhibition in cholangiocarcinoma.

Cholangiocarcinomas (CCAs) are rare but aggressive tumours of the bile ducts, which are often diagnosed at an advanced stage and have poor outcomes on systemic therapy. Somatic alterations with therapeutic implications have been identified in almost half of CCAs, in particular in intrahepatic CCA (iCCA), the subtype arising from bile ducts within the liver. Among patients with CCA, fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements occur almost exclusively in iCCA, where they are estimated to be found in up to 10-15% of patients. Clinical trials for selective FGFR kinase inhibitors have shown consistent activity of these agents in previously treated patients with iCCA harbouring FGFR alterations. Current FGFR kinase inhibitors show differences in their structure, mechanisms of target engagement, and specificities for FGFR1, 2, 3 and 4 and other related kinases. These agents offer the potential to improve outcomes in FGFR-driven CCA, and the impact of variations in the molecular profiles of the FGFR inhibitors on efficacy, safety, acquired resistance mechanisms, and patients' health-related quality of life remains to be fully characterized. The most common adverse event associated with FGFR inhibitors is hyperphosphatemia, an on-target off-tumour effect of FGFR1 inhibition, and strategies to manage this include dose adjustment, chelators, and the use of a low phosphate diet. As FGFR inhibitors and other targeted agents enter the clinic for use in FGFR-driven CCA, molecular testing for actionable mutations and monitoring for the emergence of acquired resistance will be essential.

COVID-19 in cancer patients on systemic anti-cancer therapies: outcomes from the CAPITOL (COVID-19 Cancer PatIenT Outcomes in North London) cohort study.

BACKGROUND: Patients with cancer are hypothesised to be at increased risk of contracting COVID-19, leading to changes in treatment pathways in those treated with systemic anti-cancer treatments (SACT). This study investigated the outcomes of patients receiving SACT to assess whether they were at greater risk of contracting COVID-19 or having more severe outcomes. METHODS: Data was collected from all patients receiving SACT in two cancer centres as part of CAPITOL (COVID-19 Cancer PatIenT Outcomes in North London). The primary outcome was the effect of clinical characteristics on the incidence and severity of COVID-19 infection in patients on SACT. We used univariable and multivariable models to analyse outcomes, adjusting for age, gender and comorbidities. RESULTS: A total of 2871 patients receiving SACT from 2 March to 31 May 2020 were analysed; 68 (2.4%) were diagnosed with COVID-19. Cancer patients receiving SACT were more likely to die if they contracted COVID-19 than those who did not [adjusted (adj.) odds ratio (OR) 9.84; 95% confidence interval (CI) 5.73-16.9]. Receiving chemotherapy increased the risk of developing COVID-19 (adj. OR 2.99; 95% CI = 1.72-5.21), with high dose chemotherapy significantly increasing risk (adj. OR 2.36, 95% CI 1.35-6.48), as did the presence of comorbidities (adj. OR 2.29; 95% CI 1.19-4.38), and having a respiratory or intrathoracic neoplasm (adj. OR 2.12; 95% CI 1.04-4.36). Receiving targeted treatment had a protective effect (adj. OR 0.53; 95% CI 0.30-0.95). Treatment intent (curative versus palliative), hormonal- or immunotherapy and solid versus haematological cancers had no significant effect on risk. CONCLUSION: Patients on SACT are more likely to die if they contract COVID-19. Those on chemotherapy, particularly high dose chemotherapy, are more likely to contract COVID-19, while targeted treatment appears to be protective.

The impact of Oncotype DX breast cancer assay results on clinical practice: a UK experience.

BACKGROUND: Genomic tests are increasingly being used by clinicians when considering adjuvant chemotherapy for patients with oestrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2-) breast cancer. The Oncotype DX breast recurrence score assay was the first test available in the UK National Health Service. This study looked at how UK clinicians were interpreting Recurrence Scores (RS) in everyday practice. METHODS: RS, patient and tumour characteristics and adjuvant therapy details were retrospectively collected for 713 patients from 14 UK cancer centres. Risk by RS-pathology-clinical (RSPC) was calculated and compared to the low/intermediate/risk categories, both as originally defined (RS < 18, 18-30 and > 30) and also using redefined boundaries (RS < 11, 11-25 and > 25). RESULTS: 49.8%, 36.2% and 14% of patients were at low (RS < 18), intermediate (RS 18-30) and high (RS > 30) risk of recurrence, respectively. Overall 26.7% received adjuvant chemotherapy. 49.2% of those were RS > 30; 93.3% of patients were RS > 25. Concordance between RS and RSPC improved when intermediate risk was defined as RS 11-25. CONCLUSIONS: This real-world data demonstrate the value of genomic tests in reducing the use of adjuvant chemotherapy in breast cancer. Incorporating clinical characteristics or RSPC scores gives additional prognostic information which may also aid clinicians' decision making.