Introduction
Pembrolizumab is a novel immunotherapy which blocks the immunoregulatory receptor PD-1 on T-cells, preventing tumours evading the immune system. It enables the immune system to detect and destroy malignant cells, and has proven to be highly successful in the treatment of a range of cancers including non-small cell lung cancer (NSCLC). However, when the COVID-19 pandemic hit the United Kingdom in March 2020, fears of vulnerable lung cancer patients acquiring the virus while attending hospital for their pembrolizumab led to the decision to switch to a newly licenced dosing regimen. This dosing regimen involved giving a higher dose of 400 mg pembrolizumab, and a longer interval of 6 weeks between doses, compared to the standard doses of 200 mg or 2 mg/kg given every 3 weeks. Concerns of staff regarding toxicities of the new regimen led to the development of this study.
Methods
All patients with advanced NSCLC who had been treated with at least one cycle of pembrolizumab between the 01/09/19 and 08/01/21 by the oncology department in Ninewells Hospital, Dundee, were included in this retrospective study. The patients were divided into two groups based on whether they had been treated with pembrolizumab 200mg every 3 weeks, or 400mg pembrolizumab every 6 weeks. The data collected from patients was age, gender, dose and number of cycles of pembrolizumab, reported toxicities and their grading, and any reasons for stopping pembrolizumab. The database Chemocare was used to identify patient toxicities, and these were graded using the “Guideline for the Management of Immunotherapy Toxicities in Adult Haematology and Oncology patients” published by the North Cancer Alliance, and then cross-referenced with the Common Terminology Criteria for Adverse Events guidance (CTCAE) . Further information regarding toxicities was obtained using the databases Wisdom and ICE.
Results
42 NSCLC patients had received 200mg pembrolizumab every 3 weeks and 46 patients received 400mg pembrolizumab every 6 weeks. In the 3-weekly group, 38 patients (90.5%) reported some level of toxicity after starting on pembrolizumab. In the 6-weekly group, 35 patients (76.1%) reported some level of toxicity. In both groups the most common toxicity was fatigue, followed by shortness of breath, skin rash, nausea, and itch. There were 4 cases (9.5% of patients) of Grade 3-5 toxicities in the 3 weekly pembrolizumab group (severe skin reaction, two cases of colitis and bursitis) and 5 cases (10.9% of patients) of Grade 3-5 toxicities in the 6-weekly dosing group (two skin reactions, pneumonitis, colitis and severe fatigue).
Conclusion
The results of this study demonstrated that there was no difference in the number of grade 3-5 toxicities experienced in either group. Clinicians can be reassured that patients are not being put at increased risk of toxicities due to the change to 400mg given every 6 weeks as a result of the COVID-19 pandemic. There was a higher number of toxicities reported overall in the 3-weekly pembrolizumab dosing group, however this may be due to other factors such as reduced patient contact as a result of the COVID pandemic, leading to underreporting by patients.
Keywords
covid-19, Pembrolizumab toxicities