ABSTRACT
Introduction: Incidence rates of renal-cell carcinoma have increased by more than a third within the last decade.1 VEGF inhibitors were the mainstay of treatment options in the first-line setting up until the NICE Technology Appraisal in 2020 recommended avelumab plus axitinib combination for untreated advanced RCC within the Cancer Drugs Fund.2 Since then, the use of immunotherapy plus oral VEGF inhibitor has showed promising results in patients with good, intermediate or poor risk disease. The Javelin 101 trial demonstrated progression-free survival was significantly longer with avelumab plus axitinib than with the standard of care, sunitinib, however adverse events occurred in 99.5% of patients who received the combination.3 The complexity lies with the overlap of immunotherapy and VEGF inhibitor adverse events and how to distinguish between the two in order to effectively manage these. With the introduction of pharmacy-led clinics, a major role of the pharmacist has been toxicity management in this cohort of patients. Aim and objectives: To compare and quantify the incidence of common adverse events and resulting dose modifications and treatment delays between the Javelin 101 trial with a real-world cohort of patients treated at Mount Vernon Cancer Centre, MVCC. Methods: Electronic health records were retrospectively scrutinized for all patients who received avelumab plus axitinib treatment at MVCC between June 2020 and June 2021. Patients who commenced treatment in June 2021 or who had 1 cycle or less of treatment were excluded. Clinical data based on dose delays, adverse events and dose modifications was collected, collated and analysed. Results: A total of 36 patients were analysed and 97.2% experienced an adverse event. 52.7% of patients needed dose modifications of axitinib and 5.5% had a dose escalation. Comparatively the Javelin study had 42.2% of patients requiring a dose reduction and 10.8% received 1 dose escalation. Avelumab is given as a flat dose. Most common reasons for dose reductions at MVCC included diarrhoea, stomatitis, rash and palmar-plantar erythema. Dose reductions and dose delays are standard practice for managing toxicities from avelumab and axitinib. Hypothyroidism was the most common adverse event, affecting 50% of patients studied (Female 70%: Male 42%). Patients experienced diarrhoea (42%) throughout their treatment which is largely attributed to axitinib. This was effectively managed through dose delays. Due to Covid-19, patients were reviewed in telephone clinics hence hypertension primarily managed by GPs;hence dose delays due to elevated BP were not seen. Dyspnoea and cough symptoms required further investigation. A significant number of patients ended up with Covid-19 infections resulting in treatment delays. Others had pulmonary embolisms and quickly resumed their treatment once on anticoagulation. Some patients with transaminitis were managed with long term steroids resulting in extended dose delays. Conclusions: The occurrence of the adverse events in real-world data significantly differed in some areas to the Javelin 101 trial. The lack of face-to-face reviews due to the Covid-19 pandemic may have contributed to this. The non-medical prescriber pharmacist led clinics played a major role in managing avelumab and axitinib adverse events.